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Musakhanian J, Osborne DW. Understanding Microemulsions and Nanoemulsions in (Trans)Dermal Delivery. AAPS PharmSciTech 2025; 26:31. [PMID: 39794642 DOI: 10.1208/s12249-024-02997-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 11/07/2024] [Indexed: 01/13/2025] Open
Abstract
Continuously explored in pharmaceuticals, microemulsions and nanoemulsions offer drug delivery opportunities that are too significant to ignore, namely safe delivery of clinically relevant drug doses across biological membranes. Their effectiveness as drug vehicles in mucosal and (trans)dermal delivery is evident from the volume of published literature. Commonly, their ability to enhance skin permeation is attributed to dispersion size, a characteristic closely related to solubilization capacity. However, the literature falls short on distinctions between microemulsions and nanoemulsions for definitions, behavior, or specific differences in their mechanisms of action in (trans)dermal delivery. The focus is typically on surfactant/cosurfactant ratio and droplet size but the role of mesostructures or the effect of cosolvent (Csol), oil (O) or water (W) on permeation profile remain poorly explained. Towards a deeper understanding of these vehicles in (trans)dermal drug delivery, this review begins with their conceptual and practical distinctions before delving into the published works for less obvious but potentially important underlying mechanisms; notably composition and the competitive positioning of system constituents in the resulting microstructures and subsequent effect(s) these may have on skin structures and drug permeability. For practical purposes, this review focuses on formulation systems based on ternary diagrams with commonly accepted non-ionic surfactants, cosurfactants, cosolvents, and oils used in pharmaceutical applications.
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Zhang H, Wu A, Nan X, Yang L, Zhang D, Zhang Z, Liu H. The Application and Pharmaceutical Development of Etomidate: Challenges and Strategies. Mol Pharm 2024; 21:5989-6006. [PMID: 39495089 DOI: 10.1021/acs.molpharmaceut.4c00325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2024]
Abstract
Etomidate is a synthetic imidazole anesthetic that exerts hypnotic effects by potentiating the action of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) or directly activating the anionic GABA (GABAA) receptor. It stands out among many anesthetics because of its multiple advantages, such as good hemodynamic stability and minimal inhibition of spontaneous respiration. However, its low water solubility and side effects, such as adrenal cortex inhibition and myoclonus, have limited the clinical application of this drug. To address these issues, extensive research has been conducted on the drug delivery of etomidate in recent decades, which has led to the emergence of different etomidate preparations. Despite so many etomidate preparations, so far some of the toxic side effects have not yet been effectively addressed. Herein we discuss the pharmaceutical design of etomidate that may resolve the above problem. We also propose targeted strategies for future research on etomidate preparations and discuss the feasibility of different administration routes and dosage forms to expand the application of this drug. Through this review, we hope to draw more attention to the potential of etomidate and its application challenges and provide valuable insights into the development of new etomidate preparations.
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Affiliation(s)
- Hao Zhang
- School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, People's Republic of China
- Department of Pharmacy, Zigong First People's Hospital, Zigong, Sichuan 643000, People's Republic of China
| | - Ailing Wu
- Department of Anesthesiology, Second People's Hospital of Neijiang, Southwest Medical University, Neijiang, Sichuan 641000, People's Republic of China
- Department of Anesthesiology, First People's Hospital of Neijiang, Neijiang, Sichuan 641099, People's Republic of China
| | - Xichen Nan
- School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, People's Republic of China
| | - Luhan Yang
- School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, People's Republic of China
| | - Dan Zhang
- School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, People's Republic of China
| | - Zhuo Zhang
- School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, People's Republic of China
| | - Hao Liu
- School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, People's Republic of China
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Losada-Barreiro S, Celik S, Sezgin-Bayindir Z, Bravo-Fernández S, Bravo-Díaz C. Carrier Systems for Advanced Drug Delivery: Improving Drug Solubility/Bioavailability and Administration Routes. Pharmaceutics 2024; 16:852. [PMID: 39065549 PMCID: PMC11279846 DOI: 10.3390/pharmaceutics16070852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 06/14/2024] [Accepted: 06/20/2024] [Indexed: 07/28/2024] Open
Abstract
The disadvantages of some conventional drugs, including their low bioavailability, poor targeting efficiency, and important side effects, have led to the rational design of drug delivery systems. In particular, the introduction of drug delivery systems is a potential approach to enhance the uptake of therapeutic agents and deliver them at the right time and in the right amount of concentration at the required site, as well as open new strategies for effective illness treatment. In this review, we provide a basic understanding of drug delivery systems with an emphasis on the use of cyclodextrin-, polymer- and surfactant-based delivery systems. These systems are very attractive because they are biocompatible and biodegradable nanomaterials with multifunctional components. We also provide some details on their design considerations and their use in a variety of medical applications by employing several routes of administration.
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Affiliation(s)
- Sonia Losada-Barreiro
- Departamento de Química-Física, Facultade de Química, Universidade de Vigo, 36200 Vigo, Pontevedra, Spain;
| | - Sumeyye Celik
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Ankara University, 06560 Ankara, Turkey (Z.S.-B.)
| | - Zerrin Sezgin-Bayindir
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Ankara University, 06560 Ankara, Turkey (Z.S.-B.)
| | - Sofía Bravo-Fernández
- Dentistry Department, Primary Health Unit, Galician Health Service (SERGAS), Calle Mourin s/n, 15330 Ortigueira, A Coruña, Spain;
| | - Carlos Bravo-Díaz
- Departamento de Química-Física, Facultade de Química, Universidade de Vigo, 36200 Vigo, Pontevedra, Spain;
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Abonashey SG, Hassan HAFM, Shalaby MA, Fouad AG, Mobarez E, El-Banna HA. Formulation, pharmacokinetics, and antibacterial activity of florfenicol-loaded niosome. Drug Deliv Transl Res 2024; 14:1077-1092. [PMID: 37957473 DOI: 10.1007/s13346-023-01459-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/19/2023] [Indexed: 11/15/2023]
Abstract
The growing interest in employing nano-sized pharmaceutical formulations in veterinary medicine has prompted the exploration of the novel nanocarriers' ability to augment the therapeutic outcome. In this study, we harnessed niosomes, spherical nanocarriers formed through non-ionic surfactant self-assembly, to enhance the therapeutic efficacy of the broad-spectrum antibiotic florfenicol. Pre-formulation studies were conducted to identify the optimal parameters for preparing florfenicol-loaded niosomes (FLNs). These studies revealed that the formulation that consisted of Span 60, cholesterol, and dihexadecyl phosphate (DDP) at a molar ratio of 1:1:0.1 exhibited the highest entrapment efficiency (%EE) and uniform size distribution. In vitro antibacterial testing demonstrated the niosomal capacity to significantly reduce florfenicol minimum inhibitory concentration (MIC) against E. coli and S. aureus. Pharmacokinetic profiles of free florfenicol and FLN were assessed following oral administration of 30 mg florfenicol/kg body weight to healthy or E. coli-infected chickens. FLN exhibited a substantially higher maximum plasma concentration (Cmax) of florfenicol compared to free florfenicol. Furthermore, FLN showed significantly higher area under the curve (AUC0-t) than free florfenicol as revealed from the relative bioavailability studies. Lethal dose (LD) 50 values for both free florfenicol and FLN exceeded 5 g/kg of body weight, indicating high safety profile. Assessment of mortality protection in mice against lethal E. coli infections showed the significantly higher capability of FLN to improve the survival rate (75%) than free florfenicol (25%). Collectively, these findings demonstrate the niosomal ability to improve the oral bioavailability as well as the antibacterial activity of the incorporated veterinary antibiotic florfenicol.
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Affiliation(s)
- Shimaa G Abonashey
- Department of Biochemistry, Animal Health Research Institute, Dokki, Giza, Egypt
| | - Hatem A F M Hassan
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
- School of Life and Medical Sciences, University of Hertfordshire Hosted By Global Academic Foundation, New Administrative Capital, Cairo, Egypt.
| | - Mostafa A Shalaby
- Pharmacology Department, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt
| | - Amr Gamal Fouad
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
| | - Elham Mobarez
- Department of Biochemistry, Animal Health Research Institute, Dokki, Giza, Egypt
| | - Hossny A El-Banna
- Pharmacology Department, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt
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Srivastav AK, Karpathak S, Rai MK, Kumar D, Misra DP, Agarwal V. Lipid based drug delivery systems for oral, transdermal and parenteral delivery: Recent strategies for targeted delivery consistent with different clinical application. J Drug Deliv Sci Technol 2023; 85:104526. [DOI: 10.1016/j.jddst.2023.104526] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
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Kesharwani D, Das Paul S, Paliwal R, Satapathy T. Development, QbD based optimization and in vitro characterization of Diacerein loaded nanostructured lipid carriers for topical applications. JOURNAL OF RADIATION RESEARCH AND APPLIED SCIENCES 2023. [DOI: 10.1016/j.jrras.2023.100565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/03/2023]
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Kesharwani D, Das Paul S, Paliwal R, Satapathy T. Exploring potential of diacerin nanogel for topical application in arthritis: Formulation development, QbD based optimization and pre-clinical evaluation. Colloids Surf B Biointerfaces 2023; 223:113160. [PMID: 36736175 DOI: 10.1016/j.colsurfb.2023.113160] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 12/21/2022] [Accepted: 01/19/2023] [Indexed: 01/21/2023]
Abstract
Diacerein (DCN) is a chondroprotective agent which shows inadequate oral bioavailability along with gastrointestinal side effects. This study is intended to develop a topical novel DCN delivery system. DCN nanogel was prepared by emulsion solvent diffusion technique. The formulation was optimized by response surface methodology by taking two independent variables, concentration of carbopol 940 and eudragit RSPO and three dependent variables, particle size, % entrapment efficiency (EE) and % drug release at 24 h. The optimized formulation had adequat% EE, % drug release at 24 h and particle size. The particle size for optimized nanogel was 190.3 nm with % EE of 83.51% whereas % drug release at 24 h was found 90.13%. The optimized DCN nanogel was analyzed by differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (DTIR) and transmission electron microscopy (TEM) studies. The drug release kinetic study has shown that the gel followed Higuchi's model and the diffusion was anomalous in nature. The nanogel was characterized for physical examination, viscosity, homogeneity and stability parameters and the results obtained were found upto the mark. The ex-vivo permeation study data was in correlation with results of in-vitro study. In-vivo anti-arthritic study proved the efficacy of developed formulation for arthritis in Freund's Adjuvant Arthritic model. This research work has proved the significant potential of innovated product for arthritis by topical route, as it overcomes the drawbacks of oral route, highly efficient, sustained and targeted the release of drug without any accumulation and toxicity.
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Affiliation(s)
| | - Swarnali Das Paul
- Shri Shankaracharya College of Pharmaceutical Sciences, Shri Shankaracharya Professional University, Bhilai, Chhattisgarh, India.
| | - Rishi Paliwal
- Nanomedicine and Bioengineering Research Laboratory, Department of Pharmacy, Indira Gandhi National Tribal University, Amarkantak, Madhya Pradesh, India.
| | - Trilochan Satapathy
- University College of Pharmacy, Chhattisgarh Swami Vivekanand Technical University, Bhilai, Chhattisgarh, India
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Khan R, Mirza MA, Aqil M, Alex TS, Raj N, Manzoor N, Naseef PP, Saheer Kuruniyan M, Iqbal Z. In Vitro and In Vivo Investigation of a Dual-Targeted Nanoemulsion Gel for the Amelioration of Psoriasis. Gels 2023; 9:gels9020112. [PMID: 36826282 PMCID: PMC9957534 DOI: 10.3390/gels9020112] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 01/24/2023] [Accepted: 01/25/2023] [Indexed: 01/31/2023] Open
Abstract
Psoriasis, due to its unique pathological manifestations and the limited success of existing therapeutic modalities, demands dedicated domain research. Our group has developed nanotherapeutics consisting of bioactives such as Thymoquinone (TQ) and Fulvic acid (FA), which have been successfully incorporated into a Nanoemulsion gel (NEG), taking kalonji oil as oil phase. The composition is aimed at ameliorating psoriasis with better therapeutic outcomes. TQ is a natural bio-active that has been linked to anti-psoriatic actions. FA has anti-inflammatory actions due to its free radical and oxidant-scavenging activity. Our previous publication reports the formulation development of the NEG, where we overcame the pharmaco-technical limitations of combining the above two natural bioactives. In vitro evaluation of the optimized NEG was carried out, which showed an enhanced dissolution rate and skin permeation of TQ. This work furthers the pharmaceutical progression of dual-targeted synergistic NEG to treat psoriasis. A suitable animal model, BALB/c mice, has been used to conduct the in vivo studies, which revealed the effective anti-psoriatic action of TQ. Molecular docking studies corroborated the results and revealed a good binding affinity for both the targets of TNF-α (Tumor necrosis factor) and IL-6 (Interlukin-6). Tissue uptake by Confocal laser scanning microscopy (CLSM), a skin interaction study of the gel formulation, and an antioxidant free radical scavenging assay (1-1 Diphenyl-2-picrylhydrazyl DPPH) were also carried out. It was concluded that the NEG may be effective in treating psoriasis with minimal side effects.
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Affiliation(s)
- Rahmuddin Khan
- Department of Pharmaceutics, School of Pharmaceutical Education & Research (SPER), Jamia Hamdard, New Delhi 110062, India
| | - Mohd. Aamir Mirza
- Department of Pharmaceutics, School of Pharmaceutical Education & Research (SPER), Jamia Hamdard, New Delhi 110062, India
- Correspondence: (M.A.M.); (Z.I.); Tel.: +91-9213378765 (M.A.M.); +91-9811733016 (Z.I.)
| | - Mohd Aqil
- Department of Pharmaceutics, School of Pharmaceutical Education & Research (SPER), Jamia Hamdard, New Delhi 110062, India
| | - Thomson Santosh Alex
- Department of Pharmaceutics, School of Pharmaceutical Education & Research (SPER), Jamia Hamdard, New Delhi 110062, India
| | - Nafis Raj
- Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India
| | - Nikhat Manzoor
- Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India
| | | | - Mohamed Saheer Kuruniyan
- Department of Dental Technology, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia
| | - Zeenat Iqbal
- Department of Pharmaceutics, School of Pharmaceutical Education & Research (SPER), Jamia Hamdard, New Delhi 110062, India
- Correspondence: (M.A.M.); (Z.I.); Tel.: +91-9213378765 (M.A.M.); +91-9811733016 (Z.I.)
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Kharat P, Chary PS, Bhavana V, Rajana N, Devabattula G, Godugu C, Singh SB, Mehra NK. Thymoquinone-Loaded Essential Oil-Based Emulgel as an Armament for Anti-psoriatic Activity. AAPS PharmSciTech 2022; 24:26. [PMID: 36550259 DOI: 10.1208/s12249-022-02482-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 12/05/2022] [Indexed: 12/24/2022] Open
Abstract
Essential oils consist of oxygenated structures of secondary metabolites of aromatic plants with anti-psoriatic activities. Tea tree oil (TTO) is an essential oil with good anti-microbial and anti-inflammatory properties, exhibiting reduced levels of IL-1, IL-8, and PGE 2. Thymoquinone (TMQ) is popular herb in traditional medicine with known therapeutic benefits in several diseases and ailments. The ternary phase diagram was prepared with the weight ratio of Smix (Tween® 80:Labrasol®): oil:water ratio for o/w emulsion preparation. The globule size was 16.54 ± 0.13 nm, and PDI around 0.22 ± 0.01 of the TTO-TMQ emulsion and found thermodynamically stable. The percentage drug content was found in the range of 98.97 ± 0.62 to 99.45 ± 0.17% with uniformity of the ThymoGel using Carbopol®. The extensive physicochemical properties were studied using different analytical techniques, and in vitro drug release was performed using Franz-diffusion apparatus. Anti-psoriatic activity of the formulations was studied using Imiquimod-induced psoriasis-like inflammation model in male Balb/c mice and parameters like PASI score, ear thickness, and spleen to body weight index were determined as well as histological staining, ELISA, skin compliance, and safety evaluation of TTO were performed. The combination of essential oils with TMQ shows synergistic activity and efficiently reduces the psoriasis disease condition.
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Affiliation(s)
- Pratik Kharat
- Pharmaceutical Nanotechnology Research Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India, 500037
| | - Padakanti Sandeep Chary
- Pharmaceutical Nanotechnology Research Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India, 500037
| | - Valamla Bhavana
- Pharmaceutical Nanotechnology Research Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India, 500037
| | - Naveen Rajana
- Pharmaceutical Nanotechnology Research Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India, 500037
| | - Geetanjali Devabattula
- Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India, 500037
| | - Chandraiah Godugu
- Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India, 500037
| | - Shashi Bala Singh
- Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India, 500037
| | - Neelesh Kumar Mehra
- Pharmaceutical Nanotechnology Research Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India, 500037.
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Kawish S, Hasan N, Beg S, Qadir A, Jain GK, Aqil M, Ahmad FJ. Docetaxel-loaded borage seed oil nanoemulsion with improved antitumor activity for solid tumor treatment: Formulation development, in vitro, in silico and in vivo evaluation. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
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Quadir SS, Saharan V, Choudhary D, Harish, Jain CP, Joshi G. Nano-strategies as Oral Drug Delivery Platforms for Treatment of Cancer: Challenges and Future Perspectives. AAPS PharmSciTech 2022; 23:152. [PMID: 35606661 DOI: 10.1208/s12249-022-02301-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 05/09/2022] [Indexed: 11/30/2022] Open
Abstract
Oral drug administration is the oldest and widely used method for drug administration. The objectives behind developing an oral drug delivery for the treatment of cancer are to achieve low cost treatment by utilizing novel techniques to target cancer through gut-associated lymphoid tissue (GALT) and to enhance patient comfort and compliance through a hospital-free treatment leading to "Chemotherapy at Home." Unfortunately, due to the physiological environment of the GIT and physicochemical properties of drug candidate, the efficacy of oral drug delivery methods is limited in the treatment of cancer. Due to their low hydrophilicity, high P-gp efflux and restricted intestinal permeability most of the anti-cancer drugs fail to achieve oral bioavailability. The review focuses on the efforts, challenges, opportunities and studies conducted by scientists worldwide on the oral administration of anticancer medications via nanocarriers such as liposomes, SLNs and dendrimers, because of their potential to overcome the epithelial barrier associated with GALT, as well as the applications of different polymers in targeting the cancer. The oral delivery can set newer horizons in cancer therapy to make it more patient friendly.
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Development of bioflavonoid containing chemotherapeutic delivery systems for UV-damaged skin and kangri cancer. FORUM OF CLINICAL ONCOLOGY 2021. [DOI: 10.2478/fco-2021-0012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Abstract
Background
The lower abdomen and inner thighs are most likely to become affected by kangri cancer because those areas are exposed to continuous exposure to kangri.
Objective
In this article, formulation and characterization of a water-in-oil microemulsion of 5-fluorouracil with rutin (R-5FU) for better skin penetration and inhibition of kangri cancer (skin cancer surfactant) is discussed.
Method
To produce R-5-FU microemulsions, surfactant-cosurfactant was mixed with oil. Distilled water was added dropwise with the help of a burette by gentle stirring at a constant temperature. The surfactant and co-surfactant were mixed into three particular ratios 1:1, 2:1, and 3:1. Further characterizations were performed, such as visual inspection and thermodynamic stability including a stress test and centrifugation. In visual inspection included assessment of the colour, homogeneity, and odour of the formulation of FU microemulsion.
Result
All three microemulsions, labeled RME1, RME2, and RME3, are highly stable. An oval shape of surface morphology of 5-FU was noticed by using a TEM image. The viscosity of RME3 was found to be 17.25±0.22 pa-s. The average globule size was 100–300 nm for all three RME. The results of human cadaver skin permeability are almost of the same pattern, butRME3 indicates the best skin permeability with negligible side effects on the skin.
Conclusion
The quantity of 5-FU released from all formulations at 3-hr ranged from 95.57% to 83.67%. None of the three formulations resulted in skin irritation, with irritancy score of zero (IS=0). Observation revealed no lysis, hemorrhage, or coagulation after application.
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Khan TA, Azad AK, Fuloria S, Nawaz A, Subramaniyan V, Akhlaq M, Safdar M, Sathasivam KV, Sekar M, Porwal O, Meenakshi DU, Malviya R, Miret MM, Mendiratta A, Fuloria NK. Chitosan-Coated 5-Fluorouracil Incorporated Emulsions as Transdermal Drug Delivery Matrices. Polymers (Basel) 2021; 13:3345. [PMID: 34641162 PMCID: PMC8512026 DOI: 10.3390/polym13193345] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 09/25/2021] [Accepted: 09/26/2021] [Indexed: 11/24/2022] Open
Abstract
The purpose of the present study was to develop emulsions encapsulated by chitosan on the outer surface of a nano droplet containing 5-fluorouracil (5-FU) as a model drug. The emulsions were characterized in terms of size, pH and viscosity and were evaluated for their physicochemical properties such as drug release and skin permeation in vitro. The emulsions containing tween 80 (T80), sodium lauryl sulfate, span 20, and a combination of polyethylene glycol (PEG) and T20 exhibited a release of 88%, 86%, 90% and 92%, respectively. Chitosan-modified emulsions considerably controlled the release of 5-FU compared to a 5-FU solution (p < 0.05). All the formulations enabled transportation of 5-FU through a rat's skin. The combination (T80, PEG) formulation showed a good penetration profile. Different surfactants showed variable degrees of skin drug retention. The ATR-FTIR spectrograms revealed that the emulsions mainly affected the fluidization of lipids and proteins of the stratum corneum (SC) that lead to enhanced drug permeation and retention across the skin. The present study concludes that the emulsions containing a combination of surfactants (Tween) and a co-surfactant (PEG) exhibited the best penetration profile, prevented the premature release of drugs from the nano droplet, enhanced the permeation and the retention of the drug across the skin and had great potential for transdermal drug delivery. Therefore, chitosan-coated 5-FU emulsions represent an excellent possibility to deliver a model drug as a transdermal delivery system.
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Affiliation(s)
- Taif Ali Khan
- Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan; (T.A.K.); (A.N.); (M.A.); (M.S.)
| | - Abul Kalam Azad
- Advanced Drug Delivery Laboratory, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan 25200, Pahang, Malaysia;
| | - Shivkanya Fuloria
- Faculty of Pharmacy, AIMST University, Bedong 08100, Kedah, Malaysia
- Centre of Excellence for Biomaterials and Engineering, AIMST University, Bedong 08100, Kedah, Malaysia;
| | - Asif Nawaz
- Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan; (T.A.K.); (A.N.); (M.A.); (M.S.)
| | - Vetriselvan Subramaniyan
- Faculty of Medicine, Bioscience and Nursing, MAHSA University, Jalan SP 2, Bandar Saujana Putra, Jenjarom 42610, Selangor, Malaysia;
| | - Muhammad Akhlaq
- Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan; (T.A.K.); (A.N.); (M.A.); (M.S.)
| | - Muhammad Safdar
- Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan; (T.A.K.); (A.N.); (M.A.); (M.S.)
| | - Kathiresan V. Sathasivam
- Centre of Excellence for Biomaterials and Engineering, AIMST University, Bedong 08100, Kedah, Malaysia;
- Faculty of Applied Science, AIMST University, Bedong 08100, Kedah, Malaysia
| | - Mahendran Sekar
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh 30450, Perak, Malaysia;
| | - Omji Porwal
- Department of Pharmacognosy, Tishk International University, Erbil 44001, KRG, Iraq;
| | | | - Rishabha Malviya
- Department of Pharmacy, SMAS, Galgotias University, Gautam Buddh Nagar, Greater Noida 201310, India; (R.M.); (A.M.)
| | - Mireia Mallandrich Miret
- Department of Pharmacy, Pharmaceutical Technology and Physical-Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain;
| | - Ajay Mendiratta
- Department of Pharmacy, SMAS, Galgotias University, Gautam Buddh Nagar, Greater Noida 201310, India; (R.M.); (A.M.)
| | - Neeraj Kumar Fuloria
- Faculty of Pharmacy, AIMST University, Bedong 08100, Kedah, Malaysia
- Centre of Excellence for Biomaterials and Engineering, AIMST University, Bedong 08100, Kedah, Malaysia;
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Farooq U, Rasul A, Zafarullah M, Abbas G, Rasool M, Ali F, Ahmed S, Javaid Z, Abid Z, Riaz H, Mahmood Arshad RK, Maryam S, Amna N, Asif K. Nanoemulsions as novel nanocarrieres for drug delivery across the skin: In-vitro, in-vivo evaluation of miconazole nanoemulsions for treatment of Candidiasis albicans. Des Monomers Polym 2021; 24:240-258. [PMID: 34434070 PMCID: PMC8382019 DOI: 10.1080/15685551.2021.1965724] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
Abstract
In the current research, attempt is made to fabricate a nanoemulsion (NE) containing an antifungal agent. The prepared formulation has been expected to enhance skin penetration. It is also studied for in vitro drug release and toxicity assessment. Spontaneous titration method was used for preparation of NE. Prepared NE were characterized for their charge, size, morphology, rheological behaviour, drug release profile, skin permeability. The drug permeation and skin irritation were investigated. The in vitro antifungal activity was inspected using the well agar diffusion method. Miconazole NE showed good penetration in the skin as compared to marketed products. SEM showed semispherical shapes of the droplets. Zeta potential and zeta sizer showed that size was in nano ranges having positive charge.
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Affiliation(s)
- Umar Farooq
- Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Punjab, Pakistan.,Department of Pharmacy, Rashid Latif College of Pharmacy, Lahore, Pakistan
| | - Akhtar Rasul
- Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Punjab, Pakistan
| | | | - Ghulam Abbas
- Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Punjab, Pakistan
| | - Maria Rasool
- Government College University Faisalabad, Pakistan
| | - Farman Ali
- Beaumont Hospital Dearborn, Michigan, USA
| | - Shabbir Ahmed
- Department of Chemical Engineering, Centre for Synthetic Biology, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China
| | - Zeeshan Javaid
- Department of Pharmacy, Mirpur University of Science and Technology, Mirpur, Azad Kashmir, Pakistan
| | - Zoya Abid
- Department of Pharmacy, Islam College of Pharmacy, Sialkot, Pakistan
| | - Humayun Riaz
- Department of Pharmacy, Rashid Latif College of Pharmacy, Lahore, Pakistan
| | | | - Shayan Maryam
- Department of Pharmacy, Rashid Latif College of Pharmacy, Lahore, Pakistan
| | - Naseem Amna
- Department of Pharmacy, Rashid Latif College of Pharmacy, Lahore, Pakistan
| | - Kanwal Asif
- Department of Pharmacy, Rashid Latif College of Pharmacy, Lahore, Pakistan
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15
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Ashkar A, Sosnik A, Davidovich-Pinhas M. Structured edible lipid-based particle systems for oral drug-delivery. Biotechnol Adv 2021; 54:107789. [PMID: 34186162 DOI: 10.1016/j.biotechadv.2021.107789] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 04/12/2021] [Accepted: 06/23/2021] [Indexed: 12/18/2022]
Abstract
Oral administration is the most popular and patient-compliant route for drug delivery, though it raises great challenges due to the involvement of the gastro-intestine (GI) system and the drug bioavailability. Drug bioavailability is directly related to its ability to dissolve, transport and/or absorb through the physiological environment. A great number of drugs are characterized with low water solubility due to their hydrophobic nature, thus limiting their oral bioavailability and clinical use. Therefore, new strategies aiming to provide a protective shell through the GI system and improve drug solubility and permeability in the intestine were developed to overcome this limitation. Lipid-based systems have been proposed as good candidates for such a task owing to their hydrophobic nature which allows high drug loading, drug micellization ability during intestinal digestion due to the lipid content, and the vehicle physical protective environment. The use of edible lipids with high biocompatibility paves the bench-to-bedside translation. Four main types of structured lipid-based drug delivery systems differing in the physical state of the lipid phase have been described in the literature, namely emulsions, solid lipid nanoparticles, nanostructured lipid carriers, and oleogel-based particles. The current review provides a comprehensive overview of the different structured edible lipid-based oral delivery systems investigated up to date and emphasizes the contribution of each system component to the delivery performance, and the oral delivery path of lipids.
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Affiliation(s)
- Areen Ashkar
- Laboratory of Lipids and Soft Matter, Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa 3200003, Israel
| | - Alejandro Sosnik
- Laboratory of Pharmaceutical Nanomaterials Science, Department of Materials Science and Engineering, Technion - Israel Institute of Technology, Haifa 3200003, Israel
| | - Maya Davidovich-Pinhas
- Laboratory of Lipids and Soft Matter, Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa 3200003, Israel; Russell-Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa 3200003, Israel..
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16
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Srivastava S, Haider MF, Ahmad A, Ahmad U, Arif M, Ali A. Exploring Nanoemulsions for Prostate Cancer Therapy. Drug Res (Stuttg) 2021; 71:417-428. [PMID: 34157752 DOI: 10.1055/a-1518-6606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Prostate carcinoma is typical cancer. It is the second most common cancer globally. The estimated new cases in 2020 was 191 930 and estimated deaths was 33 330. Age, family history, & genetic factors are major factors that drive prostate cancer. Although, for treating metastatic disease, the major therapies available are radiation,bisphosphonate, and palliative chemotherapy. But the major drawback is therapy is disease-driven and later becomes metastatic and requires treatment. The ability to revolutionize cancer treatment by major targeting vehicles via the exploration of nanoemulsion suggests a potential for cancer treatment. The unique property of a biphasic liquid dosage form called nanoemulsion to reach leaky tumor vasculature is due to its nano-meter oil-droplet size of 20-200 nm. Recent reporting on nanoemulsions disclose their embracing and lay alternative for re-purposing herbal and synthetic drugs and their combination especially for targeting prostate cancer formulating an obtainable nanomedicine. So, this article emphasizes the use of nanoemulsions incorporating therapeutic agents for successful and targeted delivery for prostate cancer.
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Affiliation(s)
| | | | - Afroz Ahmad
- Faculty of Pharmacy, Integral University, Lucknow, India
| | - Usama Ahmad
- Faculty of Pharmacy, Integral University, Lucknow, India
| | - Muhammad Arif
- Faculty of Pharmacy, Integral University, Lucknow, India
| | - Asad Ali
- Faculty of Pharmacy, Integral University, Lucknow, India
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17
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Enhanced anti-psoriatic activity of tacrolimus loaded nanoemulsion gel via omega 3 - Fatty acid (EPA and DHA) rich oils-fish oil and linseed oil. J Drug Deliv Sci Technol 2021. [DOI: 10.1016/j.jddst.2021.102458] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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18
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Wande DP, Cui Q, Chen S, Xu C, Xiong H, Yao J. Rediscovering Tocophersolan: A Renaissance for Nano-Based Drug Delivery and Nanotheranostic Applications. Curr Drug Targets 2021; 22:856-869. [PMID: 32525772 DOI: 10.2174/1389450121666200611140425] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2020] [Revised: 03/29/2020] [Accepted: 04/27/2020] [Indexed: 11/22/2022]
Abstract
A unique and pleiotropic polymer, d-alpha-tocopheryl polyethylene glycol succinate (Tocophersolan), is a polymeric, synthetic version of vitamin E. Tocophersolan has attracted enormous attention as a versatile excipient in different biomedical applications including drug delivery systems and nutraceuticals. The multiple inherent properties of Tocophersolan allow it to play flexible roles in drug delivery system design, including excipients with outstanding biocompatibility, solubilizer with the ability to promote drug dissolution, drug permeation enhancer, P-glycoprotein inhibitor, and anticancer compound. For these reasons, Tocophersolan has been widely used for improving the bioavailability of numerous pharmaceutical active ingredients. Tocophersolan has been approved by stringent regulatory authorities (such as the US FDA, EMA, and PMDA) as a safe pharmaceutical excipient. In this review, the current advances in nano-based delivery systems consisting of Tocophersolan, with possibilities for futuristic applications in drug delivery, gene therapy, and nanotheranostics, were systematically curated.
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Affiliation(s)
- Dickson P Wande
- State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China
| | - Qin Cui
- State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China
| | - Shijie Chen
- State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China
| | - Cheng Xu
- State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China
| | - Hui Xiong
- State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China
| | - Jing Yao
- State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China
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19
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Abu Abed OS, Mulkala S, Sharif I, Abdin AM, Elkordy AA. Lyophilization-free proliposomes for sustained release oral delivery of hydrophobic drug (cinnarazine): a comparative study. PHARMACEUTICAL TECHNOLOGY IN HOSPITAL PHARMACY 2021. [DOI: 10.1515/pthp-2021-0002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Abstract
Objectives
Cinnarizine is used for the treatment of vestibular disorders. However, its poor solubility limits its clinical uses due to many challenges. Liposomes were utilised to improve the release profile of many poorly soluble drugs. However, liposomes face many stability challenges during the storage period. This study aims to develop proliposomes designed for the oral delivery of cinnarizine with enhanced stability characteristics.
Methods
Three cinnarizine entrapping Proliposomal formulations were prepared with different ingredients and compared with their liposomal counterparts. Both vesicular approaches were characterised for their particle size, encapsulation efficiency, drug release and stability.
Results
The proliposomes were superior to liposomes in their stability and release profiles. Although no significant changes were noticed between the encapsulation efficiency percentage of the liposomal and proliposomal formulations on the day of preparation, storing the formulations for two weeks ended up with significant leakage of the drug from liposomes (p < 0.05) due to stability issues, but not in proliposomes. Moreover, the proliposomes released 100% of cinnarizine throughout the dissolution experiment in gastric fluid in comparison with the total released drug of 70% from the liposomes.
Conclusions
Proliposomes provided a successful approach to deliver lipophilic drugs orally to improve their pharmacokinetic properties by converting their crystalline nature into more amorphous agents.
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Affiliation(s)
- Omar S. Abu Abed
- Department of Health Sciences , Arab American University , Al-Reehan , Ramallah 91000 , Palestine
- Department of Pharmacy and Wellbeing , University of Sunderland , Sunderland , UK
| | - Srilikha Mulkala
- Department of Pharmacy and Wellbeing , University of Sunderland , Sunderland , UK
| | - Israa Sharif
- Department of Health and Nutrition , Palestine Polytechnic University , Hebron , Palestine
| | - Asma M. Abdin
- Department of Pharmacy and Wellbeing , University of Sunderland , Sunderland , UK
| | - Amal A. Elkordy
- Department of Pharmacy and Wellbeing , University of Sunderland , Sunderland , UK
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20
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Xie J, Huang S, Huang H, Deng X, Yue P, Lin J, Yang M, Han L, Zhang DK. Advances in the Application of Natural Products and the Novel Drug Delivery Systems for Psoriasis. Front Pharmacol 2021; 12:644952. [PMID: 33967781 PMCID: PMC8097153 DOI: 10.3389/fphar.2021.644952] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 03/01/2021] [Indexed: 12/16/2022] Open
Abstract
Psoriasis, an incurable autoimmune skin disease, is one of the most common immune-mediated disorders. Presently, numerous clinical research studies are underway, and treatment options are available. However, these treatments focus on improving symptoms of the disease and fail to achieve a radical cure; they also have certain toxic side effects. In recent years, natural products have increasingly gained attention because of their high efficiency and low toxicity. Despite their obvious therapeutic effects, natural products’ biological activity was limited by their instability, poor solubility, and low bioavailability. Novel drug delivery systems, including liposomes, lipospheres, nanostructured lipid carriers, niosomes, nanoemulsions, nanospheres, microneedles, ethosomes, nanocrystals, and foams could potentially overcome the limitations of poor water solubility and permeability in traditional drug delivery systems. Thus, to achieve a therapeutic effect, the drug can reach the epidermis and dermis in psoriatic lesions to interact with the immune cells and cytokines.
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Affiliation(s)
- Jin Xie
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shengjie Huang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Haozhou Huang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xuan Deng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Pengfei Yue
- State Key Laboratory of Innovation Medicine and High Efficiency and Energy Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
| | - Junzhi Lin
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ming Yang
- State Key Laboratory of Innovation Medicine and High Efficiency and Energy Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
| | - Li Han
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ding-Kun Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,State Key Laboratory of Innovation Medicine and High Efficiency and Energy Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
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21
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Plaza-Oliver M, Santander-Ortega MJ, Lozano MV. Current approaches in lipid-based nanocarriers for oral drug delivery. Drug Deliv Transl Res 2021; 11:471-497. [PMID: 33528830 PMCID: PMC7852471 DOI: 10.1007/s13346-021-00908-7] [Citation(s) in RCA: 97] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/13/2021] [Indexed: 02/06/2023]
Abstract
Lipid-based nanocarriers have gained much interest as carriers of drugs with poor oral bioavailability because of their remarkable advantages like low toxicity, affordable scale-up manufacture, strong biocompatibility or high drug loading efficiency. The potential of these nanocarriers lies in their ability to improve the gastrointestinal stability, solubility and permeability of their cargo drugs. However, achieving efficient oral drug delivery through lipid-based nanocarriers is a challenging task, since they encounter multiple physicochemical barriers along the gastrointestinal tract, e.g. the gastric acidic content, the intestinal mucus layer or the enzymatic degradation, that they must surmount to reach their target. These limitations may be turned into opportunities through a rational design of lipid-based nanocarriers. For that purpose, this review focuses on the main challenges of the oral route indicating the strategies undertaken for lipid-based nanocarriers in order to overcome them. Understanding their shortcomings and identifying their strengths will determine the future clinical success of lipid-based nanocarriers.
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Affiliation(s)
- María Plaza-Oliver
- Faculty of Pharmacy, Cellular Neurobiology and Molecular Chemistry of the Central Nervous System Group, 02008, Albacete, Spain
- Regional Centre of Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), 02008, Albacete, Spain
| | - Manuel Jesús Santander-Ortega
- Faculty of Pharmacy, Cellular Neurobiology and Molecular Chemistry of the Central Nervous System Group, 02008, Albacete, Spain
- Regional Centre of Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), 02008, Albacete, Spain
| | - María Victoria Lozano
- Faculty of Pharmacy, Cellular Neurobiology and Molecular Chemistry of the Central Nervous System Group, 02008, Albacete, Spain.
- Regional Centre of Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), 02008, Albacete, Spain.
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22
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Intestinal membrane transporter-mediated approaches to improve oral drug delivery. JOURNAL OF PHARMACEUTICAL INVESTIGATION 2021. [DOI: 10.1007/s40005-021-00515-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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23
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Shanmugam T, Joshi N, Kaviratna A, Ahamad N, Bhatia E, Banerjee R. Aerosol Delivery of Paclitaxel-Containing Self-Assembled Nanocochleates for Treating Pulmonary Metastasis: An Approach Supporting Pulmonary Mechanics. ACS Biomater Sci Eng 2021; 7:144-156. [PMID: 33346632 DOI: 10.1021/acsbiomaterials.0c01126] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Paclitaxel (PTX) is a potent anticancer agent, which is clinically administered by infusion for treating pulmonary metastasis of different cancers. Systemic injection of PTX is promising in treating pulmonary metastasis of various cancers but simultaneously leads to many severe complications in the body. In this study, we have demonstrated a noninvasive approach for delivering PTX to deep pulmonary tissues via an inhalable phospholipid-based nanocochleate platform and showed its potential in treating pulmonary metastasis of melanoma cancer. Nanocochleates have been previously explored for oral delivery of anticancer drugs; their application for aerosol-based administration has not been accomplished in the literature thus far. Our results showed that the PTX-carrying aerosol nanocochleates (PTX-CPTs) possessed excellent pulmonary surfactant action characterized by high surface activity and encouraging in vitro terminal airway patency when compared to the marketed Taxol formulation, which is known to contain a high amount of Cremophore EL. We observed under in vitro twin-impinger analysis that the PTX-CPT had a high tendency to get deposited in stage II (alveolar region of lungs), indicating the capability of CPT to reach the deep alveolar region. Further, while exposed to the human lung adenocarcinoma cell line (A549), the PTX-CPT showed excellent cytotoxicity mediated by enhanced cellular uptake via energy-dependent endocytosis. Aerosol-based administration of PTX-CPT in a pulmonary metastatic murine melanoma model (B16F10) resulted in significant (p < 0.05) tumor growth inhibition when compared to an intravenous dose of Taxol. Inhibition of tumor growth in aerosol-based PTX-CPT-treated animals was evident by the significant (p < 0.05) reduction in numbers of tumor nodules and percent metastasis area covered by melanoma cells in the lung when compared to other treatment groups. Overall, our finding suggests that PTX can be safely administered in the form of an aerosol using a newly developed CPT system, which serves a dual purpose as both a drug delivery carrier and a pulmonary surfactant in treating pulmonary metastasis.
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Affiliation(s)
- Thanigaivel Shanmugam
- Nanomedicine Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai 400076, India
| | - Nitin Joshi
- Nanomedicine Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai 400076, India
| | - Anubhav Kaviratna
- Nanomedicine Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai 400076, India
| | - Nadim Ahamad
- Nanomedicine Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai 400076, India
| | - Eshant Bhatia
- Nanomedicine Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai 400076, India
| | - Rinti Banerjee
- Nanomedicine Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai 400076, India
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24
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Pandey P, Gulati N, Makhija M, Purohit D, Dureja H. Nanoemulsion: A Novel Drug Delivery Approach for Enhancement of Bioavailability. RECENT PATENTS ON NANOTECHNOLOGY 2020; 14:276-293. [PMID: 32496999 DOI: 10.2174/1872210514666200604145755] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Revised: 02/26/2020] [Accepted: 03/07/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND Poor bioavailability and solubility of drugs in aqueous phase are the most important problems of newly developed chemical entities that can be improved by nanoemulsion. OBJECTIVES BCS class II and IV which are poorly soluble in water demonstrate various problems in conventional dosage forms. For the improvement of solubility, bioavailability and getting the best therapeutic effect of poorly soluble drugs nanoemulsion is the best solution. METHODS Nanoemulsion are thermodynamically unstable isotropic system with droplet size 1-100 nm in which two immiscible fluids are combined together to form one phase by using an emulsifying agent. Nanoemulsion can be designed to promote the bioavailability of API by trapping them inside. RESULTS Nanoemulsion can be developed in many dosage forms such as oral, parenteral, topical, ophthalmic dosage form in large scale using common operation at a very low cost. Large range of lipophilic drugs can be easily incorporated in nanoemulsion. CONCLUSION In this review, attention is focused on the type of nanoemulsions, their advantages over other dosage form, method for their preparation, characterization, applications and patents in various fields.
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Affiliation(s)
- Parijat Pandey
- Shri Baba Mastnath Institute of Pharmaceutical Sciences and Research, Baba Mastnath University, Rohtak - 124001, India
| | - Nisha Gulati
- Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak - 124001, India
| | - Manish Makhija
- Department of Pharmaceutical Sciences, Indira Gandhi University, Meerpur, Rewari - 123401, India
| | - Deepika Purohit
- Department of Pharmaceutical Sciences, Indira Gandhi University, Meerpur, Rewari - 123401, India
| | - Harish Dureja
- Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak - 124001, India
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25
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Barkat MA, Harshita, Rizwanullah M, Pottoo FH, Beg S, Akhter S, Ahmad FJ. Therapeutic Nanoemulsion: Concept to Delivery. Curr Pharm Des 2020; 26:1145-1166. [PMID: 32183664 DOI: 10.2174/1381612826666200317140600] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 01/23/2020] [Indexed: 11/22/2022]
Abstract
Nanoemulsions (NEs) or nanometric-scaled emulsions are transparent or translucent, optically isotropic and kinetically stable heterogeneous system of two different immiscible liquids namely, water and oil stabilized with an amphiphilic surfactant having droplet size ranges up to 100 nm. They offer a variety of potential interests for certain applications: improved deep-rooted stability; excellent optical clarity; and, enhanced bioavailability due to its nanoscale of particles. Though there is still comparatively narrow insight apropos design, development, and optimization of NEs, which mainly stems from the fact that conventional characteristics of emulsion development and stabilization only partly apply to NEs. The contemporary article focuses on the nanoemulsion dosage form journey from concept to key application in drug delivery. In addition, industrial scalability of the nanoemulsion, as well as its presence in commercial and clinical practice, are also addressed.
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Affiliation(s)
- Md A Barkat
- Department of Pharmaceutics, College of Pharmacy, University of Hafr Al Batin, Al Jamiah, Hafr Al Batin 39524, Saudi Arabia
| | - Harshita
- Department of Pharmaceutics, College of Pharmacy, University of Hafr Al Batin, Al Jamiah, Hafr Al Batin 39524, Saudi Arabia
| | - Md Rizwanullah
- Formulation Research Lab, Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
| | - Faheem H Pottoo
- Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University (Formerly University of Dammam), 31441, Dammam, Saudi Arabia
| | - Sarwar Beg
- Nanomedicine Research Lab, Department of Pharmaceutics, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, India
| | - Sohail Akhter
- Le Studium research fellow for Centre de Biophysique Moléculaire (CBM)-CNRS, University of Orléans, UPR4301, Orléans, France
| | - Farhan J Ahmad
- Nanomedicine Research Lab, Department of Pharmaceutics, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, India
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26
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Jackson J, Pandey R, Schmitt V. Part 1. Evaluation of Epigallocatechin Gallate or Tannic Acid Formulations of Hydrophobic Drugs for Enhanced Dermal and Bladder Uptake or for Local Anesthesia Effects. J Pharm Sci 2020; 110:796-806. [PMID: 33039439 DOI: 10.1016/j.xphs.2020.10.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Revised: 09/28/2020] [Accepted: 10/01/2020] [Indexed: 11/27/2022]
Abstract
Epigallocatechin gallate (EGCG) and tannic acid (TA) are known to increase the aqueous solubility and cellular uptake of the hydrophobic drugs docetaxel, paclitaxel, amphotericin B, and curcumin. In this study the practical application of gallate-based solubilization phenomena for the uptake of these drugs into dermal and bladder tissue and of lidocaine for wound healing application was studied. The penetration of all these drugs into pig skin or docetaxel into pig bladder using EGCG or TA formulations was measured. Overall, EGCG and TA particulate or propylene glycol paste formulations of drugs allowed for greatly increased levels of drug uptake into skin as compared to control formulations. EGCG/propylene glycol pastes allowed for rapid lidocaine uptake into skin. EGCG and TA formulations of docetaxel allowed for approximately 10 fold increases in bladder tissue uptake of docetaxel over tween based solutions. Morphologically, both EGCG and TA caused a mild, dose dependent exfoliation of the bladder wall. Both EGCG and TA formed injectable viscous pastes with propylene glycol which solidified in water and degraded and released lidocaine over 2-35 days. These data support the use of EGCG and TA based formulations of certain drugs for improved dermal, bladder and wound applications.
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Affiliation(s)
- John Jackson
- Faculty of Pharmaceutical Sciences, University of British Columbia, 2045 Wesbrook Mall, Vancouver, BC, Canada.
| | - Rakhi Pandey
- Faculty of Pharmaceutical Sciences, University of British Columbia, 2045 Wesbrook Mall, Vancouver, BC, Canada
| | - Veronika Schmitt
- Faculty of Pharmaceutical Sciences, University of British Columbia, 2045 Wesbrook Mall, Vancouver, BC, Canada
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27
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Ghasemiyeh P, Mohammadi-Samani S. Potential of Nanoparticles as Permeation Enhancers and Targeted Delivery Options for Skin: Advantages and Disadvantages. DRUG DESIGN DEVELOPMENT AND THERAPY 2020; 14:3271-3289. [PMID: 32848366 PMCID: PMC7429187 DOI: 10.2147/dddt.s264648] [Citation(s) in RCA: 145] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 07/24/2020] [Indexed: 12/14/2022]
Abstract
The topical route of administration has many advantages for the treatment of various skin disorders as well as cosmeceutical purposes. This route bypasses hepatic first-pass effect and systemic availability of many pharmaceuticals is limited to skin organelles such as hair follicles and so could avoid unwanted adverse reactions and increase the localized therapeutic effect. Despite such attributed advantages of the topical route, the most important challenge is skin barrier characteristics that should be overcome to obtain dermal or trans-dermal drug delivery. Different approaches have been recruited to overcome this barrier. In this review, different types of nanoparticles for skin permeation enhancement and targeted delivery to skin organelles are discussed. The potential mechanisms of each nanocarrier in permeation enhancement and dermal delivery are considered and finally, the most important advantages and disadvantages of each group are summarized.
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Affiliation(s)
- Parisa Ghasemiyeh
- Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Pharmaceutics, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Soliman Mohammadi-Samani
- Department of Pharmaceutics, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.,Center for Nanotechnology in Drug Delivery, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
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El-Sayed AS, El-Sayed MT, Rady AM, Zein N, Enan G, Shindia A, El-Hefnawy S, Sitohy M, Sitohy B. Exploiting the Biosynthetic Potency of Taxol from Fungal Endophytes of Conifers Plants; Genome Mining and Metabolic Manipulation. Molecules 2020; 25:E3000. [PMID: 32630044 PMCID: PMC7412027 DOI: 10.3390/molecules25133000] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Revised: 06/17/2020] [Accepted: 06/23/2020] [Indexed: 11/17/2022] Open
Abstract
Endophytic fungi have been considered as a repertoire for bioactive secondary metabolites with potential application in medicine, agriculture and food industry. The biosynthetic pathways by fungal endophytes raise the argument of acquisition of these machineries of such complex metabolites from the plant host. Diterpenoids "Taxol" is the most effective anticancer drug with highest annual sale, since its discovery in 1970 from the Pacific yew tree, Taxus brevifolia. However, the lower yield of Taxol from this natural source (bark of T. brevifolia), availability and vulnerability of this plant to unpredicted fluctuation with the ecological and environmental conditions are the challenges. Endophytic fungi from Taxus spp. opened a new avenue for industrial Taxol production due to their fast growth, cost effectiveness, independence on climatic changes, feasibility of genetic manipulation. However, the anticipation of endophytic fungi for industrial Taxol production has been challenged by the loss of its productivity, due to the metabolic reprograming of cells, downregulating the expression of its encoding genes with subculturing and storage. Thus, the objectives of this review were to (1) Nominate the endophytic fungal isolates with the Taxol producing potency from Taxaceae and Podocarpaceae; (2) Emphasize the different approaches such as molecular manipulation, cultural optimization, co-cultivation for enhancing the Taxol productivities; (3) Accentuate the genome mining of the rate-limiting enzymes for rapid screening the Taxol biosynthetic machinery; (4) Triggering the silenced rate-limiting genes and transcriptional factors to activates the biosynthetic gene cluster of Taxol.
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Affiliation(s)
- Ashraf S.A. El-Sayed
- Enzymology and Fungal Biotechnology Lab (EFBL), Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt; (M.T.E.-S.); (G.E.); (A.S.); (S.E.-H.)
| | - Manal T. El-Sayed
- Enzymology and Fungal Biotechnology Lab (EFBL), Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt; (M.T.E.-S.); (G.E.); (A.S.); (S.E.-H.)
| | - Amgad M. Rady
- Faculty of Biotechnology, October University for Modern Sciences and Arts, Cairo 12566, Egypt;
| | - Nabila Zein
- Chemistry Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt;
| | - Gamal Enan
- Enzymology and Fungal Biotechnology Lab (EFBL), Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt; (M.T.E.-S.); (G.E.); (A.S.); (S.E.-H.)
| | - Ahmed Shindia
- Enzymology and Fungal Biotechnology Lab (EFBL), Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt; (M.T.E.-S.); (G.E.); (A.S.); (S.E.-H.)
| | - Sara El-Hefnawy
- Enzymology and Fungal Biotechnology Lab (EFBL), Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt; (M.T.E.-S.); (G.E.); (A.S.); (S.E.-H.)
| | - Mahmoud Sitohy
- Biochemistry Department, Faculty of Agriculture, Zagazig University, Zagazig 44519, Egypt;
| | - Basel Sitohy
- Department of Clinical Microbiology, Infection and Immunology, Umeå University, SE-90185 Umeå, Sweden
- Department of Radiation Sciences, Oncology, Umeå University, SE-90185 Umeå, Sweden
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Shanmugam T, Joshi N, Ahamad N, Deshmukh A, Banerjee R. Enhanced absorption, and efficacy of oral self-assembled paclitaxel nanocochleates in multi-drug resistant colon cancer. Int J Pharm 2020; 586:119482. [PMID: 32492505 DOI: 10.1016/j.ijpharm.2020.119482] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Revised: 05/15/2020] [Accepted: 05/25/2020] [Indexed: 11/18/2022]
Abstract
Chemotherapy in drug-resistant cancers remains a challenge. Owing to associated poor bioavailability, oral administration of hydrophobic anticancer drugs like paclitaxel has been quite challenging, with the scenario being further complicated by Pgp efflux in drug-resistant tumours. We developed a novel nanocochleates (CPT) system encapsulating paclitaxel (PTX) to treat resistant colon cancer by oral administration. PTX encapsulated nanocochleates (PTX-CPT), made up of phosphatidylserine in size range of 350-600 nm with -20 ± 5.2 mV zeta potential were protected from degradation at acidic gastric pH and showed sustained PTX release over 48 h under intestinal pH condition. In vitro cytotoxicity studies on HCT-116 & HCT-15 cells (multi-drug resistant) established IC50 value of <10 and 69 nM, respectively, which was significantly lower when compared to commercial Taxol formulation. Further, the in vivo efficacy with five oral doses of 30 mg/kg PTX-CPT in an HCT-15 drug-resistant colon cancer xenograft mouse model showed more than 25 fold reduction in the tumour growth inhibition as compared to intravenous Taxol which showed just 1.94% inhibition. Interestingly, PTX-CPT treated mice also showed significantly lower proliferation index and microvessel density when compared to Taxol treated mice. Nanocochleates showed lower toxicity with at LD-50 value greater than 300 mg/kg as described in OECD 423 guideline. The enhanced efficacy of PTX-CPT speculated due to its internalization by active endocytosis, ability to escape Pgp efflux, and due to a combined effect of the pro-apoptotic and antiangiogenic role. Taken together, the results suggested the PTX-CPT a promising strategy for efficiently treating drug-resistant colon cancer orally.
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Affiliation(s)
- Thanigaivel Shanmugam
- Department of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai 400076, India
| | - Nitin Joshi
- Department of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai 400076, India
| | - Nadim Ahamad
- Department of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai 400076, India
| | - Atul Deshmukh
- Oral & Maxillofacial Pathology & Immunohistochemistry Centre, Mumbai 400003, India
| | - Rinti Banerjee
- Department of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai 400076, India.
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Ahmad N, Ahmad R, Mohammed Buheazaha T, Salman AlHomoud H, Al-Nasif HA, Sarafroz M. A comparative ex vivo permeation evaluation of a novel 5-Fluorocuracil nanoemulsion-gel by topically applied in the different excised rat, goat, and cow skin. Saudi J Biol Sci 2020; 27:1024-1040. [PMID: 32256163 PMCID: PMC7105695 DOI: 10.1016/j.sjbs.2020.02.014] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Revised: 02/13/2020] [Accepted: 02/24/2020] [Indexed: 01/05/2023] Open
Abstract
AIM OF THE STUDY 5-Fluorouracil (5-FU) can't be given orally because of very low bioavailability and produces serious adverse effects. Therefore, the main objective of this research is to develop, evaluate, and comparative effects by different nanoformulations of topical application on chemoprevention of skin cancer in different types of skin. MATERIAL AND METHODS Castor oil (oil), Transcutol HP (surfactant), and Polyethylene glycol (PEG)-400 (co-surfactant) have taken on the basis of nonionic property and highest nanoemulsion (NE)-region. Aqueous micro titration method with ultra-sonication method (based on high energy) was used for the preparation of 5-FU-NE. Optimized-5-FU-NE was stable thermodynamically, and their characterizations was performed on the basis of globule size, zeta potential, refractive index, and viscosity. Optimized-NE has been converted into 5-FU-NE-Gel with the help of Carbopol® 934 and also performed their permeation studies in the different skins (cow, goat, and rat, ex vivo) using Logan transdermal diffusion cell (DHC-6T). Optimized-5-FU-NE and 5-FU-NE-Gel were evaluated cytotoxic studies (in vitro) on the melanoma cell lines. RESULTS The permeation of 5-FU from 5-FU-NE-Gel nanoformulation for rat skin model was 1.56 times higher than the 5-FU-NE and 12.51 times higher than the 5-FU-S for the cow and goat skin model. The values of steady state flux and permeability coefficient for 5-FU-NE-Gel of rat skin were higher i.e. 12.0244 ± 1.12 µgcm-2h-1 and 1.2024 ± 0.073 × 10-2 µg cm-2h-1, respectively. Optimized-5-FU-NE and 5-FU-NE-Gel nanoformulation were found to be physically stable. SK-MEL-5 cancer cells have showed the results based on cytotoxicity studies (in vitro) that 5-FU as Optimized-5-FU-NE-Gel is much more efficacious than 5-FU-NE followed by free 5-FU. Localization of 5-FU from 5-FU-NE-Gel was higher with higher permeation in rat skin. CONCLUSION 5-FU-NE-Gel is found to be for the better to treatment of cutaneous malignancies. It can be developed 5-FU-NE-Gel could be a promising vehicle for the skin cancer chemoprevention.
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Key Words
- 5-FU, 5-Fluorouracil
- 5-FU-NE-Gel, 5-Fluorouracil Nanoemulsion Gel
- 5-Fluorouracil
- ANOVA, Analysis of variance
- BCS, Biopharmaceutical Classification System
- Cytotoxic activity
- DDTC, Diethyldithiocarbamate
- DSC, Differential Scanning Calorimetry
- Different skin permeation, chemoprevention
- Electrospray Ionization, ESI
- Er, Enhancement Ratio
- FT-IR, Fourier-transform infrared spectroscopy
- Kp, Permeability Coefficient
- Local accumulation efficiency
- NE, Nanoemulsion
- Nanoemulsion
- Nanoemulsion-gel
- PBS, phosphate buffered solution
- PDI, Polydispersity Index
- RI, Refractive index
- SEM, Scanning Electron Microscope
- TEM, Transmission Electron Microscope
- Transdermal delivery
- UHPLC-MS/MS, Ultra high performance liquid chromatography mass spectroscopy and mass spectroscopy
- ZP, Zeta Potential
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Affiliation(s)
- Niyaz Ahmad
- Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
- Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Rizwan Ahmad
- Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Taysser Mohammed Buheazaha
- Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Hussain Salman AlHomoud
- Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Hassan Ali Al-Nasif
- Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Md Sarafroz
- Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
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Nanoemulsions: A review on low energy formulation methods, characterization, applications and optimization technique. ACTA ACUST UNITED AC 2020. [DOI: 10.1016/j.matpr.2019.11.267] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Food Gastrology: A Voyage Through Our Guts. FUTURE FOODS 2019. [DOI: 10.1007/978-3-030-12995-8_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
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34
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Basic principles of drug delivery systems - the case of paclitaxel. Adv Colloid Interface Sci 2019; 263:95-130. [PMID: 30530177 DOI: 10.1016/j.cis.2018.11.004] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Revised: 11/15/2018] [Accepted: 11/15/2018] [Indexed: 01/15/2023]
Abstract
Cancer is the second cause of death worldwide, exceeded only by cardiovascular diseases. The prevalent treatment currently used against metastatic cancer is chemotherapy. Among the most studied drugs that inhibit neoplastic cells from acquiring unlimited replicative ability (a hallmark of cancer) are the taxanes. They operate via a unique molecular mechanism affecting mitosis. In this review, we show this mechanism for one of them, paclitaxel, and for other (non-taxanes) anti-mitotic drugs. However, the use of paclitaxel is seriously limited (its bioavailability is <10%) due to several long-standing challenges: its poor water solubility (0.3 μg/mL), its being a substrate for the efflux multidrug transporter P-gp, and, in the case of oral delivery, its first-pass metabolism by certain enzymes. Adequate delivery methods are therefore required to enhance the anti-tumor activity of paclitaxel. Thus, we have also reviewed drug delivery strategies in light of the various physical, chemical, and enzymatic obstacles facing the (especially oral) delivery of drugs in general and paclitaxel in particular. Among the powerful and versatile platforms that have been developed and achieved unprecedented opportunities as drug carriers, microemulsions might have great potential for this aim. This is due to properties such as thermodynamic stability (leading to long shelf-life), increased drug solubilization, and ease of preparation and administration. In this review, we define microemulsions and nanoemulsions, analyze their pertinent properties, and review the results of several drug delivery carriers based on these systems.
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Use of Lipid Nanocarriers to Improve Oral Delivery of Vitamins. Nutrients 2019; 11:nu11010068. [PMID: 30609658 PMCID: PMC6357185 DOI: 10.3390/nu11010068] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Revised: 12/01/2018] [Accepted: 12/03/2018] [Indexed: 12/12/2022] Open
Abstract
The chemical environment and enzymes in the gastrointestinal (GI) membrane limit the oral absorption of some vitamins. The GI epithelium also contributes to the poor permeability of numerous antioxidant agents. Thus, lipophilic vitamins do not readily dissolve in the GI tract, and therefore they have low bioavailability. Nanomedicine has the potential to improve the delivery efficiency of oral vitamins. In particular, the use of lipid nanocarriers for certain vitamins that are administered orally can provide improved solubility, chemical stability, epithelium permeability and bioavailability, half-life, nidus targeting, and fewer adverse effects. These lipid nanocarriers include self-emulsifying drug delivery systems (SEDDSs), nanoemulsions, microemulsions, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs). The use of nontoxic excipients and sophisticated material engineering of lipid nanosystems allows for control of the physicochemical properties of the nanoparticles and improved GI permeation via mucosal or lymphatic transport. In this review, we highlight recent progress in the development of lipid nanocarriers for vitamin delivery. In addition, the same lipid nanocarriers used for vitamins may also be effective as carriers of vitamin derivatives, and therefore enhance their oral bioavailability. One example is the incorporation of d-α-tocopheryl polyethylene glycol succinate (TPGS) as the emulsifier in lipid nanocarriers to increase the solubility and inhibit P-glycoprotein (P-gp) efflux. We also survey the concepts and discuss the mechanisms of nanomedical techniques that are used to develop vitamin-loaded nanocarriers.
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36
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Ilić T, Savić S, Batinić B, Marković B, Schmidberger M, Lunter D, Savić M, Savić S. Combined use of biocompatible nanoemulsions and solid microneedles to improve transport of a model NSAID across the skin: In vitro and in vivo studies. Eur J Pharm Sci 2018; 125:110-119. [DOI: 10.1016/j.ejps.2018.09.023] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2018] [Revised: 09/08/2018] [Accepted: 09/30/2018] [Indexed: 12/23/2022]
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Tayeb HH, Sainsbury F. Nanoemulsions in drug delivery: formulation to medical application. Nanomedicine (Lond) 2018; 13:2507-2525. [DOI: 10.2217/nnm-2018-0088] [Citation(s) in RCA: 78] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Nanoscale oil-in-water emulsions (NEs), heterogeneous systems of two immiscible liquids stabilized by emulsifiers or surfactants, show great potential in medical applications because of their attractive characteristics for drug delivery. NEs have been explored as therapeutic carriers for hydrophobic compounds via various routes of administration. NEs provide opportunities to improve drug delivery via alternative administration routes. However, deep understanding of the NE manufacturing and functionalization fundamentals, and how they relate to the choice of administration route and pharmacological profile is still needed to ease the clinical translation of NEs. Here, we review the diversity of medical applications for NEs and how that governs their formulation, route of administration, and the emergence of increasing sophistication in NE design for specific application.
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Affiliation(s)
- Hossam H Tayeb
- Australian Institute for Bioengineering & Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia
- Faculty of Applied Medical Sciences, King Abdul Abdul-Aziz University, Jeddah, Kingdom of Saudi Arabia
| | - Frank Sainsbury
- Australian Institute for Bioengineering & Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia
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Rai VK, Mishra N, Yadav KS, Yadav NP. Nanoemulsion as pharmaceutical carrier for dermal and transdermal drug delivery: Formulation development, stability issues, basic considerations and applications. J Control Release 2017; 270:203-225. [PMID: 29199062 DOI: 10.1016/j.jconrel.2017.11.049] [Citation(s) in RCA: 331] [Impact Index Per Article: 41.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Revised: 11/23/2017] [Accepted: 11/29/2017] [Indexed: 12/16/2022]
Abstract
The use of nanoemulsion in augmenting dermal and transdermal effectiveness of drugs has now well established. The development of nanoemulsion based semisolid dosage forms is an active area of present research. However, thickening or liquid-to-semisolid conversion of the nanoemulsions provides opportunities to the formulation scientist to explore novel means of solving instability issues during transformation. Extending knowledge about the explicit role of nature/magnitude of zeta potential, types of emulsifiers and selection of appropriate semisolid bases could place these versatile carriers from laboratory to industrial scale. This article reviews the progressive advancement in the delivery of medicament via nanoemulsion with special reference to the dermal and transdermal administration. It is attempted to explore the most suitable semi solid dosage form for the particular type of nanoemulsion (o/w, w/o and others) and effect of particle size and zeta potential on the delivery of drugs through dermal or transdermal route. Finally, this review also highlights the basic principles and fundamental considerations of nanoemulsion manufacture, application of nanoemulsion based semisolid dosage forms in the dermal/transdermal administration and basic considerations during the nanoemulsion absorption into and through skin.
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Affiliation(s)
- Vineet Kumar Rai
- CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, U.P., India
| | - Nidhi Mishra
- CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, U.P., India
| | - Kuldeep Singh Yadav
- CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, U.P., India
| | - Narayan Prasad Yadav
- CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, U.P., India.
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Jijie R, Barras A, Boukherroub R, Szunerits S. Nanomaterials for transdermal drug delivery: beyond the state of the art of liposomal structures. J Mater Chem B 2017; 5:8653-8675. [PMID: 32264260 DOI: 10.1039/c7tb02529g] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
A wide range of biomedical materials have been proposed to meet the different needs for controlled oral or intravenous drug delivery. The advantages of oral delivery such as self-administration of a pre-determined drug dose at defined time intervals makes it the most convenient means for the delivery of small molecular drugs. It fails however to delivery therapeutic macromolecules due to rapid degradation in the stomach and size-limited transport across the epithelium. The primary mode of administration of macromolecules is presently via injection. This administration mode is not without limitations, as the invasive nature of injections elicits pain and decreases patients' compliance. Alternative routes for drug delivery have been looked for, one being the skin. Delivery of drugs via the skin is based on the therapeutics penetrating the stratum corneum (SC) with the advantage of overcoming first-pass metabolism of drugs, to deliver drugs with a short-half-life time more easily and to eliminate frequent administrations to maintain constant drug delivery. The transdermal market still remains limited to a narrow range of drugs. The low permeability of the SC to water-soluble and macromolecular drugs poses significant challenges to transdermal administration via passive diffusion through the skin, as is the case for all topically administered drug formulations intended to bring the therapeutic into the general circulation. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to the integration of skin enhancers into pharmaceutical formulations, nanoparticles based on lipid carriers have been widely considered and reviewed. While being briefly reviewed here, the main focus of this article is on current advancements using polymeric and metallic nanoparticles. Next to these passive technologies, the handful of active technologies for local and systemic transdermal drug delivery will be discussed and put into perspective. While passive approaches dominate the literature and the transdermal market, active delivery based on microneedles or iontophoresis approaches have shown great promise for transdermal drug delivery and have entered the market, in the last decade. This review gives an overall idea of the current activities in this field.
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Affiliation(s)
- Roxana Jijie
- Univ. Lille, CNRS, Centrale Lille, ISEN, Univ. Valenciennes, UMR 8520, IEMN, F-59000 Lille, France.
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Wang Q, Li C, Ren T, Chen S, Ye X, Guo H, He H, Zhang Y, Yin T, Liang XJ, Tang X. Poly(vinyl methyl ether/maleic anhydride)-Doped PEG-PLA Nanoparticles for Oral Paclitaxel Delivery To Improve Bioadhesive Efficiency. Mol Pharm 2017; 14:3598-3608. [PMID: 28892400 DOI: 10.1021/acs.molpharmaceut.7b00612] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Bioadhesive nanoparticles based on poly(vinyl methyl ether/maleic anhydride) (PVMMA) and poly(ethylene glycol) methyl ether-b-poly(d,l-lactic acid) (mPEG-b-PLA) were produced by the emulsification solvent evaporation method. Paclitaxel was utilized as the model drug, with an encapsulation efficiency of up to 90.2 ± 4.0%. The nanoparticles were uniform and spherical in shape and exhibited a sustained drug release compared with Taxol. m-NPs also exhibited favorable bioadhesive efficiency at the same time. Coumarin 6 or DiR-loaded nanoparticles with/without PVMMA (C6-m-NPs/DiR-m-NPs or C6-p-NPs/DiR-p-NPs) were used for cellular uptake and intestinal adhesion experiments, respectively. C6-m-NPs were shown to enhance cellular uptake, and caveolae/lipid raft mediated endocytosis was the primary route for the uptake of the nanoparticles. Favorable bioadhesive efficiency led to prolonged retention in the intestine reflected by the fluorescence in isolated intestines ex vivo. In a ligated intestinal loops model, C6-m-NPs showed a clear advantage for transporting NPs across the mucus layer over C6-p-NPs and free C6. The apparent permeability coefficient (Papp) of PTX-m-NPs through Caco-2/HT29 monolayers was 1.3- and 1.6-fold higher than PTX-p-NPs and Taxol, respectively, which was consistent with the AUC0-t of different PTX formulations after oral administration in rats. PTX-m-NPs also exhibited a more effective anticancer efficacy, with an IC50 of 0.2 ± 1.4 μg/mL for A549 cell lines, further demonstrating the advantage of bioadhesive nanoparticles. The bioadhesive nanoparticles m-NPs demonstrated both mucus permeation and epithelial absorption, and thus, this bioadhesive drug delivery system has the potential to improve the bioavailability of drugs that are insoluble in the gastrointestinal environment.
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Affiliation(s)
- Qian Wang
- School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016, P. R. China.,Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , Beijing 100190, P. R. China.,Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology , Beijing 100190, P. R. China.,University of Chinese Academy of Sciences , Beijing 100049, P. R. China
| | - Chan Li
- Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , Beijing 100190, P. R. China.,Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology , Beijing 100190, P. R. China.,University of Chinese Academy of Sciences , Beijing 100049, P. R. China
| | - Tianyang Ren
- School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016, P. R. China
| | - Shizhu Chen
- Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , Beijing 100190, P. R. China.,Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology , Beijing 100190, P. R. China.,University of Chinese Academy of Sciences , Beijing 100049, P. R. China
| | - Xiaoxia Ye
- Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , Beijing 100190, P. R. China.,Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology , Beijing 100190, P. R. China.,University of Chinese Academy of Sciences , Beijing 100049, P. R. China.,Department of Pharmacology, Shenyang Pharmaceutical University , Shenyang 110016, P. R. China
| | - Hongbo Guo
- Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , Beijing 100190, P. R. China.,Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology , Beijing 100190, P. R. China.,University of Chinese Academy of Sciences , Beijing 100049, P. R. China
| | - Haibing He
- School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016, P. R. China
| | - Yu Zhang
- School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016, P. R. China
| | - Tian Yin
- School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016, P. R. China
| | - Xing-Jie Liang
- Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , Beijing 100190, P. R. China.,Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology , Beijing 100190, P. R. China.,University of Chinese Academy of Sciences , Beijing 100049, P. R. China
| | - Xing Tang
- School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016, P. R. China
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41
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Ng WY, Migotto A, Ferreira TS, Lopes LB. Monoolein-alginate beads as a platform to promote adenosine cutaneous localization and wound healing. Int J Biol Macromol 2017; 102:1104-1111. [DOI: 10.1016/j.ijbiomac.2017.04.094] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2017] [Revised: 03/28/2017] [Accepted: 04/03/2017] [Indexed: 01/16/2023]
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42
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Carvalho VFM, Migotto A, Giacone DV, de Lemos DP, Zanoni TB, Maria-Engler SS, Costa-Lotufo LV, Lopes LB. Co-encapsulation of paclitaxel and C6 ceramide in tributyrin-containing nanocarriers improve co-localization in the skin and potentiate cytotoxic effects in 2D and 3D models. Eur J Pharm Sci 2017; 109:131-143. [PMID: 28735040 DOI: 10.1016/j.ejps.2017.07.023] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 07/10/2017] [Accepted: 07/18/2017] [Indexed: 12/31/2022]
Abstract
Considering that tumor development is generally multifactorial, therapy with a combination of agents capable of potentiating cytotoxic effects is promising. In this study, we co-encapsulated C6 ceramide (0.35%) and paclitaxel (0.50%) in micro and nanoemulsions containing tributyrin (a butyric acid pro-drug included for potentiation of cytotoxicity), and compared their ability to co-localize the drugs in viable skin layers. The nanoemulsion delivered 2- and 2.4-fold more paclitaxel into viable skin layers of porcine skin in vitro at 4 and 8h post-application than the microemulsion, and 1.9-fold more C6 ceramide at 8h. The drugs were co-localized mainly in the epidermis, suggesting the nanoemulsion ability for a targeted delivery. Based on this result, the nanoemulsion was selected for evaluation of the nanocarrier-mediated cytotoxicity against cells in culture (2D model) and histological changes in a 3D melanoma model. Encapsulation of the drugs individually decreased the concentration necessary to reduce melanoma cells viability to 50% (EC50) by approximately 4- (paclitaxel) and 13-fold (ceramide), demonstrating an improved nanoemulsion-mediated drug delivery. Co-encapsulation of paclitaxel and ceramide further decreased EC50 by 2.5-4.5-fold, and calculation of the combination index indicated a synergistic effect. Nanoemulsion topical administration on 3D bioengineered melanoma models for 48h promoted marked epidermis destruction, with only few cells remaining in this layer. This result demonstrates the efficacy of the nanoemulsion, but also suggests non-selective cytotoxic effects, which highlights the importance of localizing the drugs within cutaneous layers where the lesions develop to avoid adverse effects.
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Affiliation(s)
| | - Amanda Migotto
- Institute of Biomedical Sciences, University of São Paulo, Brazil
| | | | | | - Thalita B Zanoni
- School of Pharmaceutical Sciences, University of São Paulo, Brazil
| | | | | | - Luciana B Lopes
- Institute of Biomedical Sciences, University of São Paulo, Brazil.
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43
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Carvalho VF, de Lemos DP, Vieira CS, Migotto A, Lopes LB. Potential of Non-aqueous Microemulsions to Improve the Delivery of Lipophilic Drugs to the Skin. AAPS PharmSciTech 2017; 18:1739-1749. [PMID: 27757922 DOI: 10.1208/s12249-016-0643-7] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Accepted: 09/22/2016] [Indexed: 11/30/2022] Open
Abstract
In this study, non-aqueous microemulsions were developed because of the challenges associated with finding pharmaceutically acceptable solvents for topical delivery of drugs sparingly soluble in water. The formulation irritation potential and ability to modulate the penetration of lipophilic compounds (progesterone, α-tocopherol, and lycopene) of interest for topical treatment/prevention of skin disorders were evaluated and compared to solutions and aqueous microemulsions of similar composition. The microemulsions (ME) were developed with BRIJ, vitamin E-TPGS, and ethanol as surfactant-co-surfactant blend and tributyrin, isopropyl myristate, and oleic acid as oil phase. As polar phase, propylene glycol (MEPG) or water (MEW) was used (26% w/w). The microemulsions were isotropic and based on viscosity and conductivity assessment, bicontinuous. Compared to drug solutions in lipophilic vehicles, MEPG improved drug delivery into viable skin layers by 2.5-38-fold; the magnitude of penetration enhancement mediated by MEPG into viable skin increased with drug lipophilicity, even though the absolute amount of drug delivered decreased. Delivery of progesterone and tocopherol, but not lycopene (the most lipophilic compound), increased up to 2.5-fold with MEW, and higher amounts of these two drugs were released from MEW (2-2.5-fold). Both microemulsions were considered safe for topical application, but MEPG-mediated decrease in the viability of reconstructed epidermis was more pronounced, suggesting its higher potential for irritation. We conclude that MEPG is a safe and suitable nanocarrier to deliver a variety of lipophilic drugs into viable skin layers, but the use of MEW might be more advantageous for drugs in the lower range of lipophilicity.
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Martin B, Brouillet F, Franceschi S, Perez E. Evaluation of Organogel Nanoparticles as Drug Delivery System for Lipophilic Compounds. AAPS PharmSciTech 2017; 18:1261-1269. [PMID: 27480442 DOI: 10.1208/s12249-016-0587-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Accepted: 07/01/2016] [Indexed: 01/27/2023] Open
Abstract
The purpose of the study was to evaluate organogel nanoparticles as a drug delivery system by investigating their stability, according to the formulation strategy, and their release profile. The gelled nanoparticles were prepared by hot emulsification (above the gelation temperature) of an organogel in water, and cooling at room temperature. In the first step, we used DLS and DSC to select the most suitable formulations by optimizing the proportion of ingredients (HSA, PVA, castor oil) to obtain particles of the smallest size and greatest stability. Then, two lipophilic drug models, indomethacin and ketoconazole were entrapped in the nanoparticles made of castor oil gelled by 12-hydroxystearic acid. Thermal studies (DSC) confirmed that there was no significant alteration of gelling due to the entrapped drugs, even at 3% w/w. Very stable dispersions were obtained (>3 months), with gelled oil nanoparticles presenting a mean diameter between 250 and 300 nm. High encapsulation efficiency (>98%) was measured for indomethacin and ketoconazole. The release profile determined by in vitro dialysis showed an immediate release of the drug from the organogel nanoparticles, due to rapid diffusion. The study demonstrates the interest of these gelled oil nanoparticles for the encapsulation and the delivery of lipophilic active compounds.
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Nanoemulsion: Concepts, development and applications in drug delivery. J Control Release 2017; 252:28-49. [PMID: 28279798 DOI: 10.1016/j.jconrel.2017.03.008] [Citation(s) in RCA: 687] [Impact Index Per Article: 85.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Revised: 03/03/2017] [Accepted: 03/04/2017] [Indexed: 01/07/2023]
Abstract
Nanoemulsions are biphasic dispersion of two immiscible liquids: either water in oil (W/O) or oil in water (O/W) droplets stabilized by an amphiphilic surfactant. These come across as ultrafine dispersions whose differential drug loading; viscoelastic as well as visual properties can cater to a wide range of functionalities including drug delivery. However there is still relatively narrow insight regarding development, manufacturing, fabrication and manipulation of nanoemulsions which primarily stems from the fact that conventional aspects of emulsion formation and stabilization only partially apply to nanoemulsions. This general deficiency sets up the premise for current review. We attempt to explore varying intricacies, excipients, manufacturing techniques and their underlying principles, production conditions, structural dynamics, prevalent destabilization mechanisms, and drug delivery applications of nanoemulsions to spike interest of those contemplating a foray in this field.
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Kaur A, Katiyar SS, Kushwah V, Jain S. Nanoemulsion loaded gel for topical co-delivery of clobitasol propionate and calcipotriol in psoriasis. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2017; 13:1473-1482. [PMID: 28259803 DOI: 10.1016/j.nano.2017.02.009] [Citation(s) in RCA: 88] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Revised: 01/12/2017] [Accepted: 02/09/2017] [Indexed: 11/27/2022]
Abstract
Current work reports the development and optimization of clobitasol propionate (CP) and calcipotriol (CT) loaded nanoemulsion based gel for topical treatment of psoriasis. Components of nanoemulsion viz., oil and surfactant/co-surfactant were selected depending upon solubility and emulsification potential respectively. The optimized ratio of 5:3:2 of Capmul MCM C8 EP, Cremophor RH 40 and Labrafil 1944 CS was selected. Carbopol 980 was used as gelling agent to achieve final drug concentration of 0.05% w/w and 0.005% w/w respectively for CP and CT. HaCaT cell lines showed higher uptake of drug from nanoemulsion in correlation with the enhancement in penetration of both drugs in stratum corneum (SC) and viable layer from nanoemulsion and gel as compared to free drugs. Imiquimod induced psoriatic BALB/c mice revealed significantly higher anti-psoriatic activity of nanoemulsion gel as compared to free drugs and marketed formulation. The developed formulation showed negligible skin irritation despite increased penetration into the skin.
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Affiliation(s)
- Amanpreet Kaur
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar, Punjab, India
| | - Sameer S Katiyar
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar, Punjab, India
| | - Varun Kushwah
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar, Punjab, India
| | - Sanyog Jain
- Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar, Punjab, India.
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Application of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) in transdermal and topical drug delivery systems (TDDS). JOURNAL OF PHARMACEUTICAL INVESTIGATION 2017. [DOI: 10.1007/s40005-016-0300-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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48
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Rajinikanth PS, Chellian J. Development and evaluation of nanostructured lipid carrier-based hydrogel for topical delivery of 5-fluorouracil. Int J Nanomedicine 2016; 11:5067-5077. [PMID: 27785014 PMCID: PMC5063559 DOI: 10.2147/ijn.s117511] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
The aim of this study was to develop a nanostructured lipid carrier (NLC)-based hydrogel and study its potential for the topical delivery of 5-fluorouracil (5-FU). Precirol® ATO 5 (glyceryl palmitostearate) and Labrasol® were selected as the solid and liquid lipid phases, respectively. Poloxamer 188 and Solutol® HS15 (polyoxyl-15-hydroxystearate) were selected as surfactants. The developed lipid formulations were dispersed in 1% Carbopol® 934 (poly[acrylic acid]) gel medium in order to maintain the topical application consistency. The average size, zeta potential, and polydispersity index for the 5-FU-NLC were found to be 208.32±8.21 nm, -21.82±0.40 mV, and 0.352±0.060, respectively. Transmission electron microscopy study revealed that 5-FU-NLC was <200 nm in size, with a spherical shape. In vitro drug permeation studies showed a release pattern with initial burst followed by sustained release, and the rate of 5-FU permeation was significantly improved for 5-FU-NLC gel (10.27±1.82 μg/cm2/h) as compared with plain 5-FU gel (2.85±1.12 μg/cm2/h). Further, skin retention studies showed a significant retention of 5-FU from the NLC gel (91.256±4.56 μg/cm2) as compared with that from the 5-FU plain gel (12.23±3.86 μg/cm2) in the rat skin. Skin irritation was also significantly reduced with 5-FU-NLC gel as compared with 5-FU plain gel. These results show that the prepared 5-FU-loaded NLC has high potential to improve the penetration of 5-FU through the stratum corneum, with enormous retention and with minimal skin irritation, which is the prerequisite for topically applied formulations.
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Affiliation(s)
| | - Jestin Chellian
- School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
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49
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Pentyl Gallate Nanoemulsions as Potential Topical Treatment of Herpes Labialis. J Pharm Sci 2016; 105:2194-203. [PMID: 27290627 DOI: 10.1016/j.xphs.2016.04.028] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Revised: 03/30/2016] [Accepted: 04/26/2016] [Indexed: 01/25/2023]
Abstract
Previous studies have demonstrated the antiherpes activity of pentyl gallate (PG), suggesting that it could be a promising candidate for the topical treatment of human herpes labialis. PG low aqueous solubility represents a major drawback to its incorporation in topical dosage forms. Hence, the feasibility of incorporating PG into nanoemulsions, the ability to penetrate the skin, to inhibit herpes simplex virus (HSV)-1 replication, and to cause dermal sensitization or toxicity were evaluated. Oil/water nanoemulsions containing 0.5% PG were prepared by spontaneous emulsification. The in vitro PG distribution into porcine ear skin after topical application of nanoemulsions was assessed, and the in vitro antiviral activity against HSV-1 replication was evaluated. Acute dermal toxicity and risk of dermal sensitization were evaluated in rat model. Nanoemulsions presented nanometric particle size (from 124.8 to 143.7 nm), high zeta potential (from -50.1 to -66.1 mV), loading efficiency above 99%, and adequate stability during 12 months. All formulations presented anti-HSV-1 activity. PG was able to reach deeper into the dermis more efficiently from the nanoemulsion F4. This formulation as well as PG were considered safe for topical use. Nanoemulsions seem to be a safe and effective approach for topically delivering PG in the treatment of human herpes labialis infection.
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50
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Pepe D, Carvalho VF, McCall M, de Lemos DP, Lopes LB. Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel. Int J Nanomedicine 2016; 11:2009-19. [PMID: 27274232 PMCID: PMC4869655 DOI: 10.2147/ijn.s97331] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
In this study, the ability of nanocarriers containing protein transduction domains (PTDs) of various classes to improve cutaneous paclitaxel delivery and efficacy in skin tumor models was evaluated. Microemulsions (MEs) were prepared by mixing a surfactant blend (polyoxyethylene 10 oleoyl ether, ethanol and propylene glycol), monocaprylin, and water. The PTD transportan (ME-T), penetratin (ME-P), or TAT (ME-TAT) was added at a concentration of 1 mM to the plain ME. All MEs displayed nanometric size (32.3–40.7 nm) and slight positive zeta potential (+4.1 mV to +6.8 mV). Skin penetration of paclitaxel from the MEs was assessed for 1–12 hours using porcine skin and Franz diffusion cells. Among the PTD-containing formulations, paclitaxel skin (stratum corneum + epidermis and dermis) penetration at 12 hours was maximized with ME-T, whereas ME-TAT provided the lowest penetration (1.6-fold less). This is consistent with the stronger ability of ME-T to increase transepidermal water loss (2.4-fold compared to water) and tissue permeability. The influence of PTD addition on the ME irritation potential was assessed by measuring interleukin-1α expression and viability of bioengineered skin equivalents. A 1.5- to 1.8-fold increase in interleukin-1α expression was induced by ME-T compared to the other formulations, but this effect was less pronounced (5.8-fold) than that mediated by the moderate irritant Triton. Because ME-T maximized paclitaxel cutaneous localization while being safer than Triton, its efficacy was assessed against basal cell carcinoma cells and a bioengineered three-dimensional melanoma model. Paclitaxel-containing ME-T reduced cells and tissue viability by twofold compared to drug solutions, suggesting the potential clinical usefulness of the formulation for the treatment of cutaneous tumors.
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Affiliation(s)
- Dominique Pepe
- Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA
| | - Vanessa Fm Carvalho
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Melissa McCall
- Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA
| | - Débora P de Lemos
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Luciana B Lopes
- Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
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