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Shree D, Patra CN, Sahoo BM. Applications of Nanotechnology-mediated Herbal Nanosystems for Ophthalmic Drug. Pharm Nanotechnol 2024; 12:229-250. [PMID: 37587812 DOI: 10.2174/2211738511666230816090046] [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: 04/04/2023] [Revised: 06/05/2023] [Accepted: 07/13/2023] [Indexed: 08/18/2023]
Abstract
In recent years, herbal nanomedicines have gained tremendous popularity for novel drug discovery. Nanotechnology has provided several advances in the healthcare sector, emerging several novel nanocarriers that potentiate the bioavailability and therapeutic efficacy of the herbal drug. The recent advances in nanotechnology with accelerated strategies of ophthalmic nanosystems have paved a new path for overcoming the limitations associated with ocular drug delivery systems, such as low bioavailability, poor absorption, stability, and precorneal drug loss. Ophthalmic drug delivery is challenging due to anatomical and physiological barriers. Due to the presence of these barriers, the herbal drug entry into the eyes can be affected when administered by following multiple routes, i.e., topical, injectables, or systemic. However, the advancement of nanotechnology with intelligent systems enables the herbal active constituent to successfully entrap within the system, which is usually difficult to reach employing conventional herbal formulations. Herbal-loaded nanocarrier drug delivery systems demonstrated enhanced herbal drug permeation and prolonged herbal drug delivery. In this current manuscript, an extensive search is conducted for original research papers using databases Viz., PubMed, Google Scholar, Science Direct, Web of Science, etc. Further painstaking efforts are made to compile and update the novel herbal nanocarriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, nanostructure lipid carriers, micelles, niosomes, nanoemulsions, dendrimers, etc., which are mostly used for ophthalmic drug delivery system. This article presents a comprehensive survey of diverse applications used for the preventative measures and treatment therapy of varied eye disorders. Further, this article highlights the recent findings that the innovators are exclusively working on ophthalmic nanosystems for herbal drug delivery systems. The nanocarriers are promising drug delivery systems that enable an effective and supreme therapeutic potential circumventing the limitations associated with conventional ocular drug delivery systems. The nanotechnology-based approach is useful to encapsulate the herbal bioactive and prevent them from degradation and therefore providing them for controlled and sustained release with enhanced herbal drug permeation. Extensive research is still being carried out in the field of herbal nanotechnology to design an ophthalmic nanosystem with improved biopharmaceutical properties.
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Affiliation(s)
- Dipthi Shree
- Department of Pharmaceutics, Roland Institute of Pharmaceutical Sciences, Berhampur, 760010, Odisha, India
| | - Chinam Niranjan Patra
- Department of Pharmaceutics, Roland Institute of Pharmaceutical Sciences, Berhampur, 760010, Odisha, India
| | - Biswa Mohan Sahoo
- Department of Pharmaceutical Chemistry, Roland Institute of Pharmaceutical Sciences, Berhampur, 760010, Odisha, India
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2
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Mohammed Y, Holmes A, Kwok PCL, Kumeria T, Namjoshi S, Imran M, Matteucci L, Ali M, Tai W, Benson HA, Roberts MS. Advances and future perspectives in epithelial drug delivery. Adv Drug Deliv Rev 2022; 186:114293. [PMID: 35483435 DOI: 10.1016/j.addr.2022.114293] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 04/09/2022] [Indexed: 12/12/2022]
Abstract
Epithelial surfaces protect exposed tissues in the body against intrusion of foreign materials, including xenobiotics, pollen and microbiota. The relative permeability of the various epithelia reflects their extent of exposure to the external environment and is in the ranking: intestinal≈ nasal ≥ bronchial ≥ tracheal > vaginal ≥ rectal > blood-perilymph barrier (otic), corneal > buccal > skin. Each epithelium also varies in their morphology, biochemistry, physiology, immunology and external fluid in line with their function. Each epithelium is also used as drug delivery sites to treat local conditions and, in some cases, for systemic delivery. The associated delivery systems have had to evolve to enable the delivery of larger drugs and biologicals, such as peptides, proteins, antibodies and biologicals and now include a range of physical, chemical, electrical, light, sound and other enhancement technologies. In addition, the quality-by-design approach to product regulation and the growth of generic products have also fostered advancement in epithelial drug delivery systems.
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3
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Razavi MS, Ebrahimnejad P, Fatahi Y, D’Emanuele A, Dinarvand R. Recent Developments of Nanostructures for the Ocular Delivery of Natural Compounds. Front Chem 2022; 10:850757. [PMID: 35494641 PMCID: PMC9043530 DOI: 10.3389/fchem.2022.850757] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 03/11/2022] [Indexed: 12/12/2022] Open
Abstract
Ocular disorders comprising various diseases of the anterior and posterior segments are considered as the main reasons for blindness. Natural products have been identified as potential treatments for ocular diseases due to their anti-oxidative, antiangiogenic, and anti-inflammatory effects. Unfortunately, most of these beneficial compounds are characterised by low solubility which results in low bioavailability and rapid systemic clearance thus requiring frequent administration or requiring high doses, which hinders their therapeutic applications. Additionally, the therapeutic efficiency of ocular drug delivery as a popular route of drug administration for the treatment of ocular diseases is restricted by various anatomical and physiological barriers. Recently, nanotechnology-based strategies including polymeric nanoparticles, micelles, nanofibers, dendrimers, lipid nanoparticles, liposomes, and niosomes have emerged as promising approaches to overcome limitations and enhance ocular drug bioavailability by effective delivery to the target sites. This review provides an overview of nano-drug delivery systems of natural compounds such as thymoquinone, catechin, epigallocatechin gallate, curcumin, berberine, pilocarpine, genistein, resveratrol, quercetin, naringenin, lutein, kaempferol, baicalin, and tetrandrine for ocular applications. This approach involves increasing drug concentration in the carriers to enhance drug movement into and through the ocular barriers.
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Affiliation(s)
- Malihe Sadat Razavi
- Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
- Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Pedram Ebrahimnejad
- Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
- Pharmaceutical Science Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Yousef Fatahi
- Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Antony D’Emanuele
- Leicester School of Pharmacy, De Montfort University, Leicester, United Kingdom
| | - Rassoul Dinarvand
- Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
- Leicester School of Pharmacy, De Montfort University, Leicester, United Kingdom
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Makoni PA, Khamanga SM, Walker RB. Muco-adhesive clarithromycin-loaded nanostructured lipid carriers for ocular delivery: Formulation, characterization, cytotoxicity and stability. J Drug Deliv Sci Technol 2021. [DOI: 10.1016/j.jddst.2020.102171] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Hernández-Giottonini KY, Rodríguez-Córdova RJ, Gutiérrez-Valenzuela CA, Peñuñuri-Miranda O, Zavala-Rivera P, Guerrero-Germán P, Lucero-Acuña A. PLGA nanoparticle preparations by emulsification and nanoprecipitation techniques: effects of formulation parameters. RSC Adv 2020; 10:4218-4231. [PMID: 35495261 PMCID: PMC9049000 DOI: 10.1039/c9ra10857b] [Citation(s) in RCA: 131] [Impact Index Per Article: 26.2] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Accepted: 01/13/2020] [Indexed: 12/19/2022] Open
Abstract
This study presents the influence of the primary formulation parameters on the formation of poly-dl-lactic-co-glycolic nanoparticles by the emulsification-solvent evaporation, and the nanoprecipitation techniques. In the emulsification-solvent evaporation technique, the polymer and tensoactive concentrations, the organic solvent fraction, and the sonication amplitude effects were analyzed. Similarly, in the nanoprecipitation technique the polymer and tensoactive concentrations, the organic solvent fraction and the injection speed were varied. Additionally, the agitation speed during solvent evaporation, the centrifugation speeds and the use of cryoprotectants in the freeze-drying process were analyzed. Nanoparticles were characterized by dynamic light scattering, laser Doppler electrophoresis, and scanning electron microscopy, and the results were evaluated by statistical analysis. Nanoparticle physicochemical characteristics can be adjusted by varying the formulation parameters to obtain specific sizes and stable nanoparticles. Also, by adjusting these parameters, the nanoparticle preparation processes have the potential to be tuned to yield nanoparticles with specific characteristics while maintaining reproducible results.
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Affiliation(s)
| | | | | | - Omar Peñuñuri-Miranda
- Department of Chemical and Metallurgical Engineering, University of Sonora Hermosillo Mexico +52-662-259-2105
| | - Paul Zavala-Rivera
- Department of Chemical and Metallurgical Engineering, University of Sonora Hermosillo Mexico +52-662-259-2105
| | - Patricia Guerrero-Germán
- Department of Chemical and Metallurgical Engineering, University of Sonora Hermosillo Mexico +52-662-259-2105
| | - Armando Lucero-Acuña
- Department of Chemical and Metallurgical Engineering, University of Sonora Hermosillo Mexico +52-662-259-2105
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Abstract
Although the eye is an accessible organ for direct drug application, ocular drug delivery remains a major challenge due to multiple barriers within the eye. Key barriers include static barriers imposed by the cornea, conjunctiva, and retinal pigment epithelium and dynamic barriers including tear turnover and blood and lymphatic clearance mechanisms. Systemic administration by oral and parenteral routes is limited by static blood-tissue barriers that include epithelial and endothelial layers, in addition to rapid vascular clearance mechanisms. Together, the static and dynamic barriers limit the rate and extent of drug delivery to the eye. Thus, there is an ongoing need to identify novel delivery systems and approaches to enhance and sustain ocular drug delivery. This chapter summarizes current and recent experimental approaches for drug delivery to the anterior and posterior segments of the eye.
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Affiliation(s)
- Burcin Yavuz
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, 12850 East Montview Blvd., C238-V20, Aurora, CO, 80045, USA.,Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA
| | - Uday B Kompella
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, 12850 East Montview Blvd., C238-V20, Aurora, CO, 80045, USA.
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Wang X, Zhang Y, Huang J, Xia M, Liu L, Tian C, Hu R, Gui S, Chu X. Self-assembled hexagonal liquid crystalline gels as novel ocular formulation with enhanced topical delivery of pilocarpine nitrate. Int J Pharm 2019; 562:31-41. [PMID: 30878587 DOI: 10.1016/j.ijpharm.2019.02.033] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Revised: 01/29/2019] [Accepted: 02/22/2019] [Indexed: 01/04/2023]
Abstract
The aim of this paper was to develop hexagonal liquid crystalline (HII) gels that can be used as a novel ocular delivery system for pilocarpine nitrate (PN). HII gels were prepared by a vortex method using phytantriol/triglyceride/water (71.15: 3.85: 26, w/w) ternary system. The gels were characterized by crossed polarized light microscopy, small-angle X-ray scattering, differential scanning calorimetry and rheology. And, in vitro drug release behavior and ex vivo corneal permeation were investigated. Finally, preocular residence time evaluation, eye irritation test, histological examination and miotic tests were studied in vivo and compared with carbopol gel. Based on various characterization techniques, the inner structure of the gels were HII mesophase and exhibited a pseudoplastic fluid behaviour. In vitro release results revealed that PN could be released continuously from HII gel over a period of 24 h. The ex vivo apparent permeability coefficient of HII gel was 3.15-fold (P < 0.01) higher than that of the Carbopol gel. Compared with Carbopol gel, HII gel displayed longer residence time on the eyeballs surface using fluorescent labeling technology. Furthermore, the HII gel caused no ocular irritation was estimated by corneal hydration levels, Draize test and histological inspection. Additionally, in vivo miotic study showed that HII gel had a remarkably long-lasting decrease in the pupil diameter of rabbits. In conclusion, HII gels would be a promising sustained-release formulation for ocular drug delivery.
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Affiliation(s)
- Xingqi Wang
- Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui Province 230012, People's Republic of China
| | - Yong Zhang
- Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui Province 230012, People's Republic of China
| | - Jie Huang
- Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui Province 230012, People's Republic of China
| | - Mengqiu Xia
- Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui Province 230012, People's Republic of China
| | - Liu Liu
- Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui Province 230012, People's Republic of China
| | - Chunling Tian
- Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui Province 230012, People's Republic of China
| | - Rongfeng Hu
- Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui Province 230012, People's Republic of China; Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, Anhui Province 230012, People's Republic of China
| | - Shuangying Gui
- Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui Province 230012, People's Republic of China; Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, Anhui Province 230012, People's Republic of China
| | - Xiaoqin Chu
- Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui Province 230012, People's Republic of China; Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, Anhui Province 230012, People's Republic of China.
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8
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Muthumariappan S, Ng WC, Adine C, Ng KK, Davoodi P, Wang CH, Ferreira JN. Localized Delivery of Pilocarpine to Hypofunctional Salivary Glands through Electrospun Nanofiber Mats: An Ex Vivo and In Vivo Study. Int J Mol Sci 2019; 20:E541. [PMID: 30696017 PMCID: PMC6387464 DOI: 10.3390/ijms20030541] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 01/18/2019] [Accepted: 01/24/2019] [Indexed: 01/12/2023] Open
Abstract
Dry mouth or xerostomia is a frequent medical condition among the polymedicated elderly population. Systemic pilocarpine is included in the first line of pharmacological therapies for xerostomia. However, the efficacy of existing pilocarpine formulations is limited due to its adverse side effects and multiple daily dosages. To overcome these drawbacks, a localized formulation of pilocarpine targeting the salivary glands (SG) was developed in the current study. The proposed formulation consisted of pilocarpine-loaded Poly(lactic-co-glycolic acid) (PLGA)/poly(ethylene glycol) (PEG) nanofiber mats via an electrospinning technique. The nanofiber mats were fully characterized for their size, mesh porosity, drug encapsulation efficiency, and in vitro drug release. Mat biocompatibility and efficacy was evaluated in the SG organ ex vivo, and the expression of proliferation and pro-apoptotic markers at the cellular level was determined. In vivo short-term studies were performed to evaluate the saliva secretion after acute SG treatment with pilocarpine-loaded nanofiber mats, and after systemic pilocarpine for comparison purposes. The outcomes demonstrated that the pilocarpine-loaded mats were uniformly distributed (diameter: 384 ± 124 nm) in a highly porous mesh, and possessed a high encapsulation efficiency (~81%). Drug release studies showed an initial pilocarpine release of 26% (4.5 h), followed by a gradual increase (~46%) over 15 d. Pilocarpine-loaded nanofiber mats supported SG growth with negligible cytotoxicity and normal cellular proliferation and homeostasis. Salivary secretion was significantly increased 4.5 h after intradermal SG treatment with drug-loaded nanofibers in vivo. Overall, this study highlights the strengths of PLGA/PEG nanofiber mats for the localized daily delivery of pilocarpine and reveals its potential for future clinical translation in patients with xerostomia.
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Affiliation(s)
- Sujatha Muthumariappan
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, Singapore 119085, Singapore.
| | - Wei Cheng Ng
- Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore.
| | - Christabella Adine
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, Singapore 119085, Singapore.
| | - Kiaw Kiaw Ng
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, Singapore 119085, Singapore.
| | - Pooya Davoodi
- Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore.
| | - Chi-Hwa Wang
- Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore.
| | - Joao N Ferreira
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, Singapore 119085, Singapore.
- Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand.
- National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4370, USA.
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Valenti G, La Carta S, Mazzotti G, Rapisarda M, Perna S, Di Gesù R, Giorgini L, Carbone DC, Recca G, Rizzarelli P. Controlled and sustained release of a corticosteroid drug from block copolymers synthetized by ATRP. POLYM ENG SCI 2017. [DOI: 10.1002/pen.24557] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Graziella Valenti
- Istituto per i Polimeri; Compositi e Biomateriali, Consiglio Nazionale delle Ricerche Via P; Gaifami 18 Catania 95129 Italy
| | - Stefania La Carta
- Istituto per i Polimeri; Compositi e Biomateriali, Consiglio Nazionale delle Ricerche Via P; Gaifami 18 Catania 95129 Italy
| | - Giovanni Mazzotti
- Dipartimento di Chimica Industriale «Toso Montanari»; Università di Bologna Via Risorgimento 4; Bologna 40136 Italy
| | - Marco Rapisarda
- Istituto per i Polimeri; Compositi e Biomateriali, Consiglio Nazionale delle Ricerche Via P; Gaifami 18 Catania 95129 Italy
| | - Stefania Perna
- ST Microelectronics Srl; Stradale Primosole; Catania 50-95121 Italy
| | - Roberto Di Gesù
- Dipartimento di Chimica «Giacomo Ciamician»; Università di Bologna Via Selmi 2; Bologna 40126 Italy
| | - Loris Giorgini
- Dipartimento di Chimica Industriale «Toso Montanari»; Università di Bologna Via Risorgimento 4; Bologna 40136 Italy
| | - Domenico Carmelo Carbone
- Istituto per i Polimeri; Compositi e Biomateriali, Consiglio Nazionale delle Ricerche Via P; Gaifami 18 Catania 95129 Italy
| | - Giuseppe Recca
- Istituto per i Polimeri; Compositi e Biomateriali, Consiglio Nazionale delle Ricerche Via P; Gaifami 18 Catania 95129 Italy
| | - Paola Rizzarelli
- Istituto per i Polimeri; Compositi e Biomateriali, Consiglio Nazionale delle Ricerche Via P; Gaifami 18 Catania 95129 Italy
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10
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Mehra NK, Cai D, Kuo L, Hein T, Palakurthi S. Safety and toxicity of nanomaterials for ocular drug delivery applications. Nanotoxicology 2016; 10:836-60. [PMID: 27027670 DOI: 10.3109/17435390.2016.1153165] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Multifunctional nanomaterials are rapidly emerging for ophthalmic delivery of therapeutics to facilitate safe and effective targeting with improved patient compliance. Because of their extremely high area to volume ratio, nanomaterials often have physicochemical properties that are different from those of their larger counterparts. There exists a complex relationship between the physicochemical properties (composition, size, shape, charge, roughness, and porosity) of the nanomaterials and their interaction with the biological system. The eye is a very sensitive accessible organ and is subjected to intended and unintended exposure to nanomaterials. Currently, various ophthalmic formulations are available in the market, while some are underway in preclinical and clinical phases. However, the data on safety, efficacy, and toxicology of these advanced nanomaterials for ocular drug delivery are sparse. Focus of the present review is to provide a comprehensive report on the safety, biocompatibility and toxicities of nanomaterials in the eye.
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Affiliation(s)
- Neelesh K Mehra
- a Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy , Texas A&M Health Science Center , Kingsville , TX , USA
| | - Defu Cai
- a Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy , Texas A&M Health Science Center , Kingsville , TX , USA
| | - Lih Kuo
- b Department of Medical Physiology, College of Medicine , Texas A&M Health Science Center , Temple , TX , USA ;,c Department of Surgery and Scott & White Eye Institute, College of Medicine , Texas A&M Health Science Center , Temple , TX , USA
| | - Travis Hein
- c Department of Surgery and Scott & White Eye Institute, College of Medicine , Texas A&M Health Science Center , Temple , TX , USA
| | - Srinath Palakurthi
- a Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy , Texas A&M Health Science Center , Kingsville , TX , USA
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Yokozaki Y, Sakabe J, Ng B, Shimoyama Y. Effect of temperature, pressure and depressurization rate on release profile of salicylic acid from contact lenses prepared by supercritical carbon dioxide impregnation. Chem Eng Res Des 2015. [DOI: 10.1016/j.cherd.2015.05.008] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Chitosan grafted methoxy poly(ethylene glycol)-poly(ε-caprolactone) nanosuspension for ocular delivery of hydrophobic diclofenac. Sci Rep 2015; 5:11337. [PMID: 26067670 PMCID: PMC4464308 DOI: 10.1038/srep11337] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2014] [Accepted: 05/20/2015] [Indexed: 01/27/2023] Open
Abstract
This study aimed to develop a cationic nanosuspension of chitosan (CS) and methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) for ocular delivery of diclofenac (DIC). MPEG-PCL-CS block polymer was synthesized by covalent coupling of MPEG-PCL with CS. The critical micelle concentration of the MPEG-PCL-CS block polymer was 0.000692 g/L. DIC/MPEG-PCL-CS nanosuspension (mean particle size = 105 nm, zeta potential = 8 mV) was prepared and characterized by Fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The nanosuspension was very stable without apparent physical property changes after storage at 4 °C or 25 °C for 20 days, but it was unstable in the aqueous humor solution after 24 h incubation. Sustained release of the encapsulated DIC from the nanosuspension occurred over 8 h. Neither a blank MPEG-PCL-CS nanosuspension nor a 0.1% (mass fraction) DIC/MPEG-PCL-CS nanosuspension caused ocular irritation after 24 h of instillation. Enhanced penetration and retention in corneal tissue was achieved with a Nile red/MPEG-PCL-CS nanosuspension compared with a Nile red aqueous solution. In vivo pharmacokinetics studies showed enhanced pre-corneal retention and penetration of the DIC/MPEG-PCL-CS nanosuspension, which resulted in a higher concentration of DIC (Cmax) in the aqueous humor and better bioavailability compared with commercial DIC eye drops (P < 0.01).
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Reimondez-Troitiño S, Csaba N, Alonso MJ, de la Fuente M. Nanotherapies for the treatment of ocular diseases. Eur J Pharm Biopharm 2015; 95:279-93. [PMID: 25725262 DOI: 10.1016/j.ejpb.2015.02.019] [Citation(s) in RCA: 127] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Revised: 02/09/2015] [Accepted: 02/16/2015] [Indexed: 10/23/2022]
Abstract
The topical route is the most frequent and preferred way to deliver drugs to the eye. Unfortunately, the very low ocular drug bioavailability (less than 5%) associated with this modality of administration, makes the efficient treatment of several ocular diseases a significant challenge. In the last decades, it has been shown that specific nanocarriers can interact with the ocular mucosa, thereby increasing the retention time of the associated drug onto the eye, as well as its permeability across the corneal and conjunctival epithelium. In this review, we comparatively analyze the mechanism of action and specific potential of the most studied nano-drug delivery carriers. In addition, we present the success achieved until now using a number of nanotherapies for the treatment of the most prevalent ocular pathologies, such as infections, inflammation, dry eye, glaucoma, and retinopathies.
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Affiliation(s)
- S Reimondez-Troitiño
- Nano-oncologicals Lab, Translational Medical Oncology Group, Health Research Institute of Santiago de Compostela (IDIS), Clinical University Hospital of Santiago de Compostela (CHUS), Santiago de Compostela, Spain; Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Health Research Institute of Santiago de Compostela (IDIS), Dept. of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Univ. of Santiago de Compostela, Santiago de Compostela, Spain
| | - N Csaba
- Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Health Research Institute of Santiago de Compostela (IDIS), Dept. of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Univ. of Santiago de Compostela, Santiago de Compostela, Spain
| | - M J Alonso
- Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Health Research Institute of Santiago de Compostela (IDIS), Dept. of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Univ. of Santiago de Compostela, Santiago de Compostela, Spain
| | - M de la Fuente
- Nano-oncologicals Lab, Translational Medical Oncology Group, Health Research Institute of Santiago de Compostela (IDIS), Clinical University Hospital of Santiago de Compostela (CHUS), Santiago de Compostela, Spain.
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14
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Li J, Wu L, Wu W, Wang B, Wang Z, Xin H, Xu Q. A potential carrier based on liquid crystal nanoparticles for ophthalmic delivery of pilocarpine nitrate. Int J Pharm 2013; 455:75-84. [DOI: 10.1016/j.ijpharm.2013.07.057] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2013] [Revised: 07/11/2013] [Accepted: 07/27/2013] [Indexed: 02/01/2023]
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15
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Nair K L, Jagadeeshan S, Nair S A, Kumar GSV. Folic acid conjugated δ-valerolactone-poly(ethylene glycol) based triblock copolymer as a promising carrier for targeted doxorubicin delivery. PLoS One 2013; 8:e70697. [PMID: 23990912 PMCID: PMC3749165 DOI: 10.1371/journal.pone.0070697] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2013] [Accepted: 06/04/2013] [Indexed: 11/19/2022] Open
Abstract
The aim of this study is to test the hypothesis that the newly synthesized poly(δ-valerolactone)/poly(ethylene glycol)/poly(δ-valerolactone) (VEV) copolymer grafted with folic acid would impart targetability and further enhance the anti-tumor efficacy of doxorubicin (DOX). Here, folic acid conjugated VEV (VEV-FOL) was synthesized by a modified esterification method and characterized using IR and NMR. DOX loaded VEV-FOL micelles were synthesized using a novel solvent evaporation method and were obtained with a mean diameter of 97 nm with high encapsulation efficiency and sustained in vitro release profile. Comparative studies of polymer micelles with and without folate for cellular uptake and cytotoxicity were done on folate receptor-positive breast cancer cell line, MDAMB231. The intracellular uptake tests showed significant increase in folate micellar uptake when compared to non-folate-mediated micelles. MTT assay followed by apoptosis assays clearly indicated that folate decorated micelles showed significantly better cytotoxicity (IC50 = 0.014 µM) and efficiency to induce apoptosis than other treated groups. Moreover, a significant G2/M arrest was induced by DOX loaded VEV-FOL micelles at a concentration where free drug failed to show any activity. Thus, our results show that the folic acid-labeled VEV copolymer is a promising biomaterial with controlled and sustainable tumor targeting ability for anticancer drugs which can open new frontiers in the area of targeted chemotherapy.
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Affiliation(s)
- Lekha Nair K
- Chemical Biology, Rajiv Gandhi Centre for Biotechnology, Poojappura, Kerala, India
| | - Sankar Jagadeeshan
- Cancer Research, Rajiv Gandhi Centre for Biotechnology, Poojappura, Kerala, India
| | - Asha Nair S
- Cancer Research, Rajiv Gandhi Centre for Biotechnology, Poojappura, Kerala, India
| | - G. S. Vinod Kumar
- Chemical Biology, Rajiv Gandhi Centre for Biotechnology, Poojappura, Kerala, India
- * E-mail:
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Patel A, Cholkar K, Agrahari V, Mitra AK. Ocular drug delivery systems: An overview. World J Pharmacol 2013; 2:47-64. [PMID: 25590022 PMCID: PMC4289909 DOI: 10.5497/wjp.v2.i2.47] [Citation(s) in RCA: 514] [Impact Index Per Article: 42.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2012] [Revised: 03/21/2013] [Accepted: 04/04/2013] [Indexed: 02/06/2023] Open
Abstract
The major challenge faced by today’s pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreo-retinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments. Also, recent developments with other ocular drug delivery strategies employing in situ gels, implants, contact lens and microneedles have been discussed.
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Abd El-Rehim HA, Swilem AE, Klingner A, Hegazy ESA, Hamed AA. Developing the Potential Ophthalmic Applications of Pilocarpine Entrapped Into Polyvinylpyrrolidone–Poly(acrylic acid) Nanogel Dispersions Prepared By γ Radiation. Biomacromolecules 2013; 14:688-98. [DOI: 10.1021/bm301742m] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Hassan A. Abd El-Rehim
- Department of Polymers, National Center for Radiation Research and Technology, Nasr City,
Cairo 11371, Egypt
| | - Ahmed E. Swilem
- Department of Chemistry, Faculty of Science, Ain Shams University, Abbassia, Cairo 11566, Egypt
| | - Anke Klingner
- Department of Physics, Basic Science, German University in Cairo, Al−Tagmoa Al−Khames, New Cairo 13411, Egypt
| | - El-Sayed A. Hegazy
- Department of Polymers, National Center for Radiation Research and Technology, Nasr City,
Cairo 11371, Egypt
| | - Ashraf A. Hamed
- Department of Chemistry, Faculty of Science, Ain Shams University, Abbassia, Cairo 11566, Egypt
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