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Firoz F, Yousef T, Asser Y, Thaer RM, Sammour RMF. Thermo-activated in situ rectal gel preparation for Ibuprofen using eutectic mixture. Eur J Pharm Sci 2024; 200:106843. [PMID: 38950638 DOI: 10.1016/j.ejps.2024.106843] [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: 11/27/2023] [Revised: 06/05/2024] [Accepted: 06/24/2024] [Indexed: 07/03/2024]
Abstract
This study aimed to develop a thermosensitive in situ gel formulation for rectal delivery of Ibuprofen as an efficient alternative dosage form. Utilizing poloxamer 188, poloxamer 407, and HPMC via cold technique method, a thermosensitive in situ gel was successfully prepared. The concentration of Ibuprofen in the formulations was 1.2 % (w/w). The prepared gels underwent assessment for clarity, gelation temperature, gelation time, gel strength, spread ability, syringe-ability, pH, viscosity, FTIR, and drug content. The selected formulations exhibited a gelation temperature within the range of 30 °C to 36 °C, with consistent amount of drug soluble in the formulations (93 % - 110 %). Mucoadhesive studies, in vitro release tests, ex vivo modeling of drug release, kinetic studies modeling, and histopathology testing were also conducted. The formulation comprising 18 % poloxamer 407, 12 % poloxamer 188, and 1 % sodium chloride (FS15) demonstrated suitable gelation temperature and desirable drug release rate. In vitro drug release tests indicated completion within one hour for both FS10 (20 % P407 & 10 % P188) and FS15 (18 % P407 & 12 % P188), with consistent and predictable release patterns observed through kinetic modeling analysis. Microscopic histopathology examination confirmed the safety of the selected formula, exhibiting no irritation in the mucosal membrane of the sheep. In conclusion, Ibuprofen thermosensitive in situ gel presents a promising and convenient strategy as a rectal carrier and an alternative dosage form to solid suppositories.
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Affiliation(s)
- Fathima Firoz
- Bpharm graduate, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates
| | - Tafika Yousef
- Bpharm graduate, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates
| | - Yosra Asser
- Bpharm graduate, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates
| | - Reem Mohammed Thaer
- Bpharm graduate, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates
| | - Rana M F Sammour
- Pharmaceutics Department, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates.
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Hirun N, Kraisit P, Santhan S. Mixed Micellar Gel of Poloxamer Mixture for Improved Solubilization of Poorly Water-Soluble Ibuprofen and Use as Thermosensitive In Situ Gel. Pharmaceutics 2024; 16:1055. [PMID: 39204400 PMCID: PMC11359337 DOI: 10.3390/pharmaceutics16081055] [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: 07/08/2024] [Revised: 08/05/2024] [Accepted: 08/08/2024] [Indexed: 09/04/2024] Open
Abstract
The aqueous solution of binary mixtures of amphiphilic copolymers is a potential platform for fabricating mixed polymeric micelles for pharmaceutical applications, particularly in developing drug delivery depots for a poorly water-soluble compound. This study fabricated and investigated binary mixtures of poloxamer 403 (P403) and poloxamer 407 (P407) at varying P403:P407 molar ratios to develop a vehicle for the poorly water-soluble compound, using ibuprofen as a model drug. The cooperative formation of mixed micelles was obtained, and the solubility of ibuprofen in the binary mixtures was enhanced compared to the solubility in pure water and an aqueous single P407 solution. The binary mixture with the P403:P407 molar ratio of 0.75:0.25 at a total polymer concentration of 19% w/v exhibited the temperature dependence of micellization and sol-to-gel characteristics of the thermosensitive mixed micellar gels. It possessed suitable micellization and gelation characteristics for in situ gelling systems. The release of ibuprofen from the thermosensitive mixed micellar depots was sustained through a diffusion-controlled mechanism. The findings can aid in formulating binary mixtures of P403 and P407 to achieve the desired properties of mixed micelles and micellar gels.
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Affiliation(s)
- Namon Hirun
- Thammasat University Research Unit in Smart Materials and Innovative Technology for Pharmaceutical Applications (SMIT-Pharm), Faculty of Pharmacy, Thammasat University, Pathumthani 12120, Thailand; (P.K.); (S.S.)
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Bakhrushina EO, Dubova AI, Nikonenko MS, Grikh VV, Shumkova MM, Korochkina TV, Krasnyuk II, Krasnyuk II. Thermosensitive Intravitreal In Situ Implant of Cefuroxime Based on Poloxamer 407 and Hyaluronic Acid. Gels 2023; 9:693. [PMID: 37754374 PMCID: PMC10530203 DOI: 10.3390/gels9090693] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/22/2023] [Accepted: 08/25/2023] [Indexed: 09/28/2023] Open
Abstract
The main method of treatment and prevention of endophthalmitis is a combination of intravitreal and topical administration of antibiotics, such as cefuroxime moxifloxacin or vancomycin. However, this method is ineffective due to the rapid elimination of the drug. This problem can be solved with the help of intravitreal in situ injection systems, which are injected with a syringe into the vitreous body and provide prolonged action of the drug at the focus of inflammation. Under the influence of temperature, the liquid drug undergoes a phase transition and turns into a gel after injection. This ensures its prolonged action. The study aimed to develop an intravitreal in situ cefuroxime delivery system for the treatment of endophthalmitis based on a thermosensitive biodegradable composition of poloxamer 407 and hyaluronic acid. A combination of poloxamer Kolliphor® P407, Kolliphor® P188, and PrincipHYAL® hyaluronic acids of different molecular weights was used as a delivery system. The potency of cefuroxime solid dispersion with polyvinylpyrrolidone-10000, polyethylene glycol-400, and polyethylene glycol-1500 in a 1:2 ratio was studied for prolonged action compared to cefuroxime substance. The experimental formulations were studied for the parameters of gelation temperature in a long-term test (4 months), pH, and release of cefuroxime using dialysis bags. To study the distribution parameter in the vitreous body, an in vitro model (1/13) was developed, which was a hollow agar sphere filled with 1% (w/v) polyacrylate gel. For the superior formulations, a HET-CAM test (chorioallantoic membrane test) was performed to determine the absence of irritant effects. According to the study results, a formulation containing a solid dispersion of cefuroxime:PEG-400 (1:2), the matrix of which contained 18% (w/v) Kolliphor® P407 poloxamer, 3% (w/v) Kolliphor® P188 poloxamer, and 0.5% (w/v) hyaluronic acid (1400-1800), was selected. This sample had an average gelation temperature of 34.6 °C, pH 6.7 ± 0.5, and a pronounced prolonged effect. Only 7.6% was released in 3 h of the experiment, whereas about 38% of cefuroxime was released in 72 h. No irritant effect on the chorioallantoic membrane was observed for any formulations studied.
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Affiliation(s)
- Elena O. Bakhrushina
- Department of Pharmaceutical Technology, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia; (E.O.B.); (T.V.K.); (I.I.K.)
| | - Anastasia I. Dubova
- Student of Educational Department, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia; (A.I.D.); (M.S.N.)
| | - Maria S. Nikonenko
- Student of Educational Department, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia; (A.I.D.); (M.S.N.)
| | - Viktoriya V. Grikh
- Department of Analytical, Physical and Colloidal Chemistry, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia; (V.V.G.); (I.I.K.J.)
| | - Marina M. Shumkova
- Department of Pharmaceutical Technology, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia; (E.O.B.); (T.V.K.); (I.I.K.)
- PHARMA-PREMIUM Scientific Educational Center, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia
| | - Tatyana V. Korochkina
- Department of Pharmaceutical Technology, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia; (E.O.B.); (T.V.K.); (I.I.K.)
| | - Ivan I. Krasnyuk
- Department of Analytical, Physical and Colloidal Chemistry, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia; (V.V.G.); (I.I.K.J.)
| | - Ivan I. Krasnyuk
- Department of Pharmaceutical Technology, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia; (E.O.B.); (T.V.K.); (I.I.K.)
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Popescu I, Constantin M, Bercea M, Coșman BP, Suflet DM, Fundueanu G. Poloxamer/Carboxymethyl Pullulan Aqueous Systems-Miscibility and Thermogelation Studies Using Viscometry, Rheology and Dynamic Light Scattering. Polymers (Basel) 2023; 15:polym15081909. [PMID: 37112056 PMCID: PMC10143542 DOI: 10.3390/polym15081909] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 04/12/2023] [Accepted: 04/14/2023] [Indexed: 04/29/2023] Open
Abstract
Thermally-induced gelling systems based on Poloxamer 407 (PL) and polysaccharides are known for their biomedical applications; however, phase separation frequently occurs in mixtures of poloxamer and neutral polysaccharides. In the present paper, the carboxymethyl pullulan (CMP) (here synthesized) was proposed for compatibilization with poloxamer (PL). The miscibility between PL and CMP in dilute aqueous solution was studied by capillary viscometry. CMP with substitution degrees higher than 0.5 proved to be compatible with PL. The thermogelation of concentrated PL solutions (17%) in the presence of CMP was monitored by the tube inversion method, texture analysis and rheology. The micellization and gelation of PL in the absence or in the presence of CMP were also studied by dynamic light scattering. The critical micelle temperature and sol-gel transition temperature decrease with the addition of CMP, but the concentration of CMP has a peculiar influence on the rheological parameters of the gels. In fact, low concentrations of CMP decrease the gel strength. With a further increase in polyelectrolyte concentration, the gel strength increases until 1% CMP, then the rheological parameters are lowered again. At 37 °C, the gels are able to recover the initial network structure after high deformations, showing a reversible healing process.
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Affiliation(s)
- Irina Popescu
- "Petru Poni" Institute of Macromolecular Chemistry, 41-A Grigore Ghica Voda Alley, 700487 Iasi, Romania
| | - Marieta Constantin
- "Petru Poni" Institute of Macromolecular Chemistry, 41-A Grigore Ghica Voda Alley, 700487 Iasi, Romania
| | - Maria Bercea
- "Petru Poni" Institute of Macromolecular Chemistry, 41-A Grigore Ghica Voda Alley, 700487 Iasi, Romania
| | - Bogdan-Paul Coșman
- "Petru Poni" Institute of Macromolecular Chemistry, 41-A Grigore Ghica Voda Alley, 700487 Iasi, Romania
| | - Dana Mihaela Suflet
- "Petru Poni" Institute of Macromolecular Chemistry, 41-A Grigore Ghica Voda Alley, 700487 Iasi, Romania
| | - Gheorghe Fundueanu
- "Petru Poni" Institute of Macromolecular Chemistry, 41-A Grigore Ghica Voda Alley, 700487 Iasi, Romania
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Mfoafo K, Omidi Y, Omidian H. Thermoresponsive mucoadhesive hybrid gels in advanced drug delivery systems. Int J Pharm 2023; 636:122799. [PMID: 36914019 DOI: 10.1016/j.ijpharm.2023.122799] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 02/22/2023] [Accepted: 03/01/2023] [Indexed: 03/13/2023]
Abstract
Thermoresponsive polymers have seen extensive use in the development of stimuli-responsive drug formulations for oral, buccal, nasal, ocular, topical, rectal, parenteral, and vaginal routes of administration. Despite their great potential, their use has been limited by various obstacles, such as undesirable high polymer concentration, wide gelation temperature, low gel strength, poor mucoadhesiveness, and short retention. Mucoadhesive polymers have been suggested to improve the mucoadhesive features of thermoresponsive gels, leading to increased drug bioavailability and efficacy. This article highlights the use of in-situ thermoresponsive mucoadhesive hydrogel blends or hybrids that have been developed and assessed in various routes of administration.
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Affiliation(s)
- Kwadwo Mfoafo
- Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, USA
| | - Yadollah Omidi
- Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, USA
| | - Hossein Omidian
- Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, USA.
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Liu X, Huang S, Ma L, Ye H, Lin J, Cai X, Shang Q, Zheng C, Xu R, Zhang D. Recent advances in wearable medical diagnostic sensors and new therapeutic dosage forms for fever in children. J Pharm Biomed Anal 2022; 220:115006. [PMID: 36007307 DOI: 10.1016/j.jpba.2022.115006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 08/05/2022] [Accepted: 08/13/2022] [Indexed: 11/17/2022]
Abstract
Fever in children is one of the most common symptoms of pediatric diseases and the most common complaint in pediatric clinics, especially in the emergency department. Diseases such as pneumonia, sepsis, and meningitis are leading causes of death in children, and the early manifestations of these diseases are accompanied by fever symptoms. Accurate diagnosis and real-time monitoring of the status of febrile children, rapid and effective identification of the cause, and treatment can have a positive impact on relieving their symptoms and improving their quality of life. In recent years, wearable diagnostic sensors have attracted special attention for their high flexibility, real-time monitoring, and sensitivity. Temperature sensors and heart rate sensors have provided new advances in detecting children's body temperature and heart rate. Furthermore, some novel formulations have also received wide attention for addressing bottlenecks in medication administration for febrile children, such as difficulty in swallowing and inaccurate dosing. In this context, the present review provides recent advances of novel wearable medical sensor devices for diagnosing fever. Moreover, the application progress of innovative dosage forms of classical antipyretic drugs for children is presented. Finally, challenges and prospects of wearable sensor-based diagnostics and novel agent-based treatment of fever in children are discussed in brief.
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Affiliation(s)
- Xuemei Liu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China
| | - Shengjie Huang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China
| | - Lele Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China
| | - Hui Ye
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China
| | - Junzhi Lin
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, PR China
| | - Xinfu Cai
- Sichuan Guangda Pharmaceutical Co. Ltd., Pengzhou 611930, PR China; National Engineering Research Center for Modernization of Traditional Chinese Medicine, Pengzhou 611930, PR China
| | - Qiang Shang
- Sichuan Guangda Pharmaceutical Co. Ltd., Pengzhou 611930, PR China; National Engineering Research Center for Modernization of Traditional Chinese Medicine, Pengzhou 611930, PR China
| | - Chuan Zheng
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, PR China.
| | - Runchun Xu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China.
| | - Dingkun Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China.
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Sun J, Sun X. Preparation of a novel tacrolimus ion sensitive ocular in situ gel and in vivo evaluation of curative effect of immune conjunctivitis. Pharm Dev Technol 2022; 27:399-405. [PMID: 35579910 DOI: 10.1080/10837450.2022.2067870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
BACKGROUND The aim of this study was to formulate a novel TAC preparation into an in situ gel for ocular drug delivery, in order to prolong the residence time on mucosal surfaces and increase patient compliance. METHODS The optimal formulation was characterized by surface morphology, gelling capacity, viscosity, stability and in vitro release. In vivo studies were also conducted to evaluate the precorneal retention and pharmacodynamic results. RESULTS In this study, the TAC in situ gel can be prepared by a simple solvent stirring method, and the optimized formulation exhibited good stability within 3 months. During storage, the initial viscosity of the formula had little change. The results of viscosity measurement showed that TAC in situ gel was typical of pseudo plastic systems and exhibited a marked increase in viscosity stimulated with STF. In vitro and in vivo studies illustrated that TAC in situ gel administration facilitated the retention and sustained release of TAC. CONCLUSIONS TAC combined with in situ gelling agents demonstrates an efficient topical drug delivery platform.
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Affiliation(s)
- Jinfu Sun
- Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Xufang Sun
- Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
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Huang CH, Hu PY, Wu QY, Xia MY, Zhang WL, Lei ZQ, Li DX, Zhang GS, Feng JF. Preparation, in vitro and in vivo Evaluation of Thermosensitive in situ Gel Loaded with Ibuprofen-Solid Lipid Nanoparticles for Rectal Delivery. Drug Des Devel Ther 2022; 16:1407-1431. [PMID: 35586185 PMCID: PMC9109935 DOI: 10.2147/dddt.s350886] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Accepted: 04/27/2022] [Indexed: 12/13/2022] Open
Abstract
Background Ibuprofen (IBU), a nonsteroidal anti-inflammatory drug, shows poor gastrointestinal absorption due to its low solubility, which limits its clinical application. Objective In the present study, we aimed to develop thermosensitive gel-mediated ibuprofen-solid lipid nanoparticles (IBU-SLN-ISG) to improve the dissolution and bioavailability of IBU after rectal delivery. Methods IBU-loaded SLNs (IBU-SLNs) were developed and optimized applying Box-Behnken design. The optimized IBU-SLNs were characterized by physicochemical parameters and morphology. Then, the optimized IBU-SLNs was incorporated into the gel and characterized for gel properties and rheology and investigated its release in vitro, pharmacokinetics in vivo, rectal irritation and rectal retention time. Results The optimized SLNs had an EE of 90.74 ± 1.40%, DL of 11.36 ± 1.20%, MPS of 166.77 ± 2.26 nm, PDI of 0.27 ± 0.08, and ZP of −21.00 ± 0.59 mV. The FTIR spectra confirmed successful encapsulation of the drug inside the nanoparticle as only peaks responsible for the lipid could be identified. This corroborated well with XRD spectra, which showed a completely amorphous state of the IBU-SLNs as compared to the crystalline nature of the pure drug. The gelation temperature of the prepared IBU-SLN-ISG was 33.30 ± 0.78°C, the gelation time was 14.67 ± 2.52 s, the gel strength was 54.00 ± 1.41 s, and the mucoadhesion was (11.54±0.37) × 102dyne/cm2. The in vitro results of IBU-SLNs and IBU-SLN-ISG showed a biphasic release pattern with initial burst release followed by sustained release. More importantly, IBU-SLN-ISG produced much better absorption of IBU and improved bioavailability in rats. In addition, IBU-SLN-ISG caused no irritation or damage to rectal tissues, and could be retained in the rectum for a long time. Conclusion Thermosensitive in situ gel loaded with IBU-solid lipid nanoparticles might be further developed as a more convenient and effective rectal dosage form.
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Affiliation(s)
- Chun-hui Huang
- School of Pharmacy, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, People’s Republic of China
- National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Nanchang, 330006, People’s Republic of China
| | - Peng-yi Hu
- National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Nanchang, 330006, People’s Republic of China
- Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, People’s Republic of China
| | - Qiu-yan Wu
- National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Nanchang, 330006, People’s Republic of China
- Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, People’s Republic of China
| | - Ming-yan Xia
- National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Nanchang, 330006, People’s Republic of China
- Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, People’s Republic of China
| | - Wen-liu Zhang
- Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, People’s Republic of China
| | - Zhi-qiang Lei
- Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, People’s Republic of China
| | - Dong-xun Li
- Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, People’s Republic of China
| | - Guo-song Zhang
- National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Nanchang, 330006, People’s Republic of China
- Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, People’s Republic of China
- Correspondence: Guo-song Zhang, National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Nanchang, 330006, People’s Republic of China, Email
| | - Jian-fang Feng
- School of Pharmacy, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, People’s Republic of China
- National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Nanchang, 330006, People’s Republic of China
- Jian-fang Feng, School of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530200, People’s Republic of China, Email
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Bai L, Lei F, Luo R, Fei Q, Zheng Z, He N, Gui S. Development of a thermosensitive in-situ gel formulations of vancomycin hydrochloride: design, preparation, in vitro and in vivo evaluation. J Pharm Sci 2022; 111:2552-2561. [DOI: 10.1016/j.xphs.2022.04.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 04/13/2022] [Accepted: 04/13/2022] [Indexed: 10/18/2022]
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Ma X, Lang J, Chen P, Yang R. Silver Nanoparticles as an Effective Antimicrobial against Otitis Media Pathogens. AIChE J 2021; 67:e17468. [PMID: 35450419 PMCID: PMC9017526 DOI: 10.1002/aic.17468] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 09/14/2021] [Indexed: 01/06/2023]
Abstract
Otitis Media (OM) is the most common reason for U.S. children to receive prescribed oral antibiotics, leading to potential to cause antibiotic resistance. To minimize oral antibiotic usage, we developed polyvinylpyrrolidone-coated silver nanoparticles (AgNPs-PVP), which completely eradicated common OM pathogens, i.e., Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) at 1.04μg/mL and 2.13μg/mL. The greater antimicrobial efficacy against S. pneumoniae was a result of the H2O2-producing ability of S. pneumoniae and the known synergistic interactions between H2O2 and AgNPs. To enable the sustained local delivery of AgNPs-PVP (e.g., via injection through perforated tympanic membranes), a hydrogel formulation of 18%(w/v)P407 was developed. Reverse thermal gelation of the AgNPs-PVP-P407 hydrogel could gel rapidly upon entering the warm auditory bullae and thereby sustained release of antimicrobials. This hydrogel-based local delivery system completely eradicated OM pathogens in vitro without cytotoxicity, and thus represents a promising strategy for treating bacterial OM without relying on conventional antibiotics.
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Affiliation(s)
- Xiaojing Ma
- Robert F. Smith School of Chemical & Biomolecular Engineering, Cornell University, Ithaca, NY 14850, USA
| | - Jiayan Lang
- Robert F. Smith School of Chemical & Biomolecular Engineering, Cornell University, Ithaca, NY 14850, USA
| | - Pengyu Chen
- Robert F. Smith School of Chemical & Biomolecular Engineering, Cornell University, Ithaca, NY 14850, USA
| | - Rong Yang
- Robert F. Smith School of Chemical & Biomolecular Engineering, Cornell University, Ithaca, NY 14850, USA
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11
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Chen Y, Lee JH, Meng M, Cui N, Dai CY, Jia Q, Lee ES, Jiang HB. An Overview on Thermosensitive Oral Gel Based on Poloxamer 407. MATERIALS 2021; 14:ma14164522. [PMID: 34443046 PMCID: PMC8399853 DOI: 10.3390/ma14164522] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 07/27/2021] [Accepted: 08/09/2021] [Indexed: 12/12/2022]
Abstract
In this review, we describe the application of thermosensitive hydrogels composed of poloxamer in medicine, especially for oral cavities. Thermosensitive hydrogels remain fluid at room temperature; at body temperature, they become more viscous gels. In this manner, the gelling system can remain localized for considerable durations and control and prolong drug release. The chemical structure of the poloxamer triblock copolymer leads to an amphiphilic aqueous solution and an active surface. Moreover, the poloxamer can gel by forming micelles in an aqueous solution, depending on its critical micelle concentration and critical micelle temperature. Owing to its controlled-release effect, a thermosensitive gel based on poloxamer 407 (P407) is used to deliver drugs with different characteristics. As demonstrated in studies on poloxamer formulations, an increase in gelling viscosity decreases the drug release rate and gel dissolution time to the extent that it prolongs the drug’s duration of action in disease treatment. This property is used for drug delivery and different therapeutic applications. Its unique route of administration, for many oral diseases, is advantageous over traditional routes of administration, such as direct application and systemic treatment. In conclusion, thermosensitive gels based on poloxamers are suitable and have great potential for oral disease treatment.
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Affiliation(s)
- Yabing Chen
- Stomatological Materials Laboratory, School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai’an 271016, China; (Y.C.); (M.M.); (N.C.); (C.-Y.D.); (Q.J.)
| | - Jeong-Ho Lee
- Department of Oral and Maxillofacial Surgery, Graduate School of Clinical Dentistry, Korea University, Seoul 08308, Korea;
| | - Mingyue Meng
- Stomatological Materials Laboratory, School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai’an 271016, China; (Y.C.); (M.M.); (N.C.); (C.-Y.D.); (Q.J.)
| | - Naiyu Cui
- Stomatological Materials Laboratory, School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai’an 271016, China; (Y.C.); (M.M.); (N.C.); (C.-Y.D.); (Q.J.)
| | - Chun-Yu Dai
- Stomatological Materials Laboratory, School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai’an 271016, China; (Y.C.); (M.M.); (N.C.); (C.-Y.D.); (Q.J.)
| | - Qi Jia
- Stomatological Materials Laboratory, School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai’an 271016, China; (Y.C.); (M.M.); (N.C.); (C.-Y.D.); (Q.J.)
| | - Eui-Seok Lee
- Department of Oral and Maxillofacial Surgery, Graduate School of Clinical Dentistry, Korea University, Seoul 08308, Korea;
- Correspondence: (E.-S.L.); (H.-B.J.)
| | - Heng-Bo Jiang
- Stomatological Materials Laboratory, School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai’an 271016, China; (Y.C.); (M.M.); (N.C.); (C.-Y.D.); (Q.J.)
- Correspondence: (E.-S.L.); (H.-B.J.)
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Li XY, Guan QX, Shang YZ, Wang YH, Lv SW, Yang ZX, Wang R, Feng YF, Li WN, Li YJ. Metal-organic framework IRMOFs coated with a temperature-sensitive gel delivering norcantharidin to treat liver cancer. World J Gastroenterol 2021; 27:4208-4220. [PMID: 34326620 PMCID: PMC8311525 DOI: 10.3748/wjg.v27.i26.4208] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/27/2021] [Accepted: 05/27/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Norcantharidin (NCTD) is suitable for the treatment of primary liver cancer, especially early and middle primary liver cancer. This compound can reduce tumors and improve immune function. However, the side effects of NCTD have limited its application. There is a marked need to reduce the side effects and increase the efficacy of NCTD. AIM To develop a nanomaterial carrier, NCTD-loaded metal-organic framework IRMOF-3 coated with a temperature-sensitive gel (NCTD-IRMOF-3-Gel), aiming to improve the anticancer activity of NCTD and reduce the drug dose. METHODS NCTD-IRMOF-3-Gel was obtained by a coordination reaction. The apparent characteristics and in vitro release of NCTD-IRMOF-3-Gel were investigated. Cell cytotoxicity assays, flow cytometry, and apoptosis experiments in mouse hepatoma (Hepa1-6) cells were used to determine the anti-liver cancer activity of NCTD-IRMOF-3-Gel in in vitro models. RESULTS The particle size of NCTD-IRMOF-3-Gel was 50-100 nm, and the particle size distribution was uniform. The release curve showed that NCTD-IRMOF-3-Gel had an obvious sustained-release effect. The cytotoxicity assays showed that the free drug NCTD and NCTD-IRMOF-3-Gel treatments markedly inhibited Hepa1-6 cell proliferation, and the inhibition rate increased with increasing drug concentration. By flow cytometry, NCTD-IRMOF-3-Gel was observed to block the Hepa1-6 cell cycle in the S and G2/M phases, and the thermosensitive gel nanoparticles may inhibit cell proliferation by inducing cell cycle arrest. Apoptosis experiments showed that NCTD-IRMOF-3-Gel induced the apoptosis of Hepa1-6 cells. CONCLUSION Our results indicated that the NCTD-IRMOF-3-Gel may be beneficial for liver cancer disease treatment.
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Affiliation(s)
- Xiu-Yan Li
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Qing-Xia Guan
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Yu-Zhou Shang
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Yan-Hong Wang
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Shao-Wa Lv
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Zhi-Xin Yang
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Rui Wang
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Yu-Fei Feng
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Wei-Nan Li
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
| | - Yong-Ji Li
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
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Metal-organic framework IRMOFs coated with a temperature-sensitive gel delivering norcantharidin to treat liver cancer. World J Gastroenterol 2021. [DOI: 10.3748/wjg.v27.i26.4203] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/17/2023] Open
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14
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Xu D, Qiu C, Wang Y, Qiao T, Cui YL. Intranasal co-delivery of berberine and evodiamine by self-assembled thermosensitive in-situ hydrogels for improving depressive disorder. Int J Pharm 2021; 603:120667. [PMID: 33933642 DOI: 10.1016/j.ijpharm.2021.120667] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 04/23/2021] [Accepted: 04/27/2021] [Indexed: 12/17/2022]
Abstract
The orally administrated antidepressants not only caused side effects such as dizziness, diarrhea, and drug resistance, but also worked slowly. Therefore, new antidepressants and preparations derived from natural medicines play an important role in the study of antidepressant drugs. It was reported that the two components of Zuojin pill, berberine (BBR) and evodiamine (EVO), were used in combination to improve depressive disorder. In our study, a self-assembled thermosensitive in-situ hydrogel was prepared to achieve sustained co-delivery of BBR and EVO. The preparation process of hydrogel consists of two steps, namely, the inclusion of the drugs and thermosensitive self-assembly of the hydrogel. In vitro experimental results indicated that the prepared hydrogel showed a good thermosensitive property under physiological temperature. The hydrogel had a slow and controlled release behavior for BBR and EVO, according with first-order equation. In vivo experimental results indicated that compared to intragastric administration of drug solution, the intranasal administration of hydrogel increased bioavailability of BBR and EVO, approximately 135 and 112 folds, respectively. The hydrogel at a low dose significantly reversed behavioral despair of the mice, improved depressive symptom of rats, and treated depressive disorder by regulating the abnormal levels of monoamine neurotransmitters (including 5-hydroxytryptamine, noradrenalin and dopamine) metabolism and related metabolic pathways such as purine, citrate cycle, scorbate and aldarate, butanoate, vitamin B6, and pyrimidine metabolism. Therefore, as a drug co-delivery system, the intranasally administrated hydrogels with a good release and high bioavailability provides a non-invasive therapeutic strategy for the clinical treatment of depression, which attains antidepressant effects by regulation of the monoamine neurotransmitters metabolism and related metabolic pathways.
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Affiliation(s)
- Dong Xu
- State Key Laboratory of Component-based Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Chao Qiu
- State Key Laboratory of Component-based Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Yue Wang
- State Key Laboratory of Component-based Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Tao Qiao
- State Key Laboratory of Component-based Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China
| | - Yuan-Lu Cui
- State Key Laboratory of Component-based Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China.
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Obaidat R, Aleih H, Mashaqbeh H, Altaani B, Alsmadi MM, Alnaief M. Development and Evaluation of Cocoa Butter Taste Masked Ibuprofen Using Supercritical Carbon Dioxide. AAPS PharmSciTech 2021; 22:106. [PMID: 33719021 DOI: 10.1208/s12249-021-01962-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 02/10/2021] [Indexed: 02/01/2023] Open
Abstract
Masking the unpleasant taste of the pharmaceutically active ingredients plays a critical role in patient acceptance, particularly for children. This work's primary objective was the preparation of taste-masked ibuprofen microparticles using cocoa butter with the assistance of supercritical fluid technology. Microparticles were prepared by dissolving ibuprofen in melted cocoa butter at 40 °C. The solution was then introduced into a supercritical fluid unit and processed at 10 MPa CO2 pressure for 30 min. The product was collected after depressurizing the system. The effect of the drug to cocoa butter ratio and the supercritical fluid units' configuration on product quality was evaluated and compared with the sample prepared by a conventional method. Physicochemical characterization of the prepared product, including particle size, crystallinity, entrapment efficiency, in vitro drug release, and product taste using a human volunteer panel was conducted. The produced microparticles were in the range of 1.42 to 15.28 μm. The entrapment efficiency of the formulated microparticles ranged from 66 to 81%. The drug:polymer ratio, the configuration of the supercritical fluid unit, and the method of preparation were found to have a critical role in the formulation of ibuprofen microparticles. Taste evaluation using human volunteers showed that microparticles containing 20% drug and processed with supercritical fluid technology were capable of masking the bitter taste of ibuprofen. In conclusion, the dispersion of ibuprofen in cocoa butter using supercritical fluid technology is a a promising innovative method to mask the bitter taste of ibuprofen.
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Mucoadhesive In Situ Rectal Gel Loaded with Rifampicin: Strategy to Improve Bioavailability and Alleviate Liver Toxicity. Pharmaceutics 2021; 13:pharmaceutics13030336. [PMID: 33807729 PMCID: PMC8001001 DOI: 10.3390/pharmaceutics13030336] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 02/24/2021] [Accepted: 03/01/2021] [Indexed: 01/11/2023] Open
Abstract
Although it is a front-line in tuberculosis treatment, rifampicin (RF) exhibits poor oral bioavailability and hepatotoxicity. Rectal mucoadhesive and in situ rectal gels were developed to overcome drug drawbacks. A RF/polyethylene glycol 6000 co-precipitate was first prepared in different ratios. Based on the drug solubility, the selected ratio was investigated for drug/polymer interaction and then incorporated into in situ rectal gels using Pluronic F127 (15%) and Pluronic F68 (10%) as a gel base and mucoadhesive polymers (HPMC, sodium alginate and chitosan). The formulations were assessed for gelation temperature and gel strength. The selected formulation was investigated for in vivo assessments. The results showed that a 1:1 drug/polymer ratio exhibited satisfying solubility with the recorded drug/polymer interaction. Depending on their concentrations, adding mucoadhesive polymers shifted the gelation temperature to lower temperatures and improved the gel strength. The selected formulation (F4) did not exhibit any anal leakage or marked rectal irritation. Using a validated chromatographic analytical method, F4 exhibited higher drug absorption with a 3.38-fold and 1.74-fold higher bioavailability when compared to oral drug suspension and solid suppositories, respectively. Toxicity studies showed unnoticeable hepatic injury in terms of biochemical, histopathological and immunohistochemical examinations. Together, F4 showed a potential of enhanced performance and also offered lower hepatic toxicity, thus offering an encouraging therapeutic alternative.
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Temperature-sensitive gel-loaded composite nanomedicines for the treatment of cervical cancer by vaginal delivery. Int J Pharm 2020; 586:119616. [PMID: 32650113 DOI: 10.1016/j.ijpharm.2020.119616] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Revised: 06/07/2020] [Accepted: 07/01/2020] [Indexed: 12/24/2022]
Abstract
In this study, toad venom (TV) and realgar were loaded into a poloxamer 188/407 (F127/F188)-based temperature-sensitive in situ gel (TISG) and encapsulated in solid lipid nanoparticles (TV-SLN) or ground nano-realgar (NR) to improve drug release and reduce local irritation after vaginal administration. The combination of TV-SLN and NR (TV-SLN/NR) greatly enhanced the inhibition of tumor cell proliferation and was most effective at a dose ratio of 2:3 (w/w). After TV-SLN/NR treatment, S and G0/G1 phase arrest were observed in HeLa and SKOV-3 cells and the inhibitory effects on proliferation were stronger than those in the conventional powder group. The gelation temperature of TV-SLN and NR-loaded TISG (TV-SLN/NR-TISG) using the selected formulation was 33 ± 0.91 °C. The cumulative release of the drug increased as the dissolution of gel progressed, showing a linear relationship (r > 0.99). TV-SLN/NR-TISG enabled the sustained release of cargo by adhesion to the vaginal mucosa and showed excellent biocompatibility during continuous administration for 7 days. We specifically demonstrated the effectiveness of the TISG for the vaginal delivery of TV-SLN and NR, supporting its important clinical implications for the treatment of cervical cancer.
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Hua S. Physiological and Pharmaceutical Considerations for Rectal Drug Formulations. Front Pharmacol 2019; 10:1196. [PMID: 31680970 PMCID: PMC6805701 DOI: 10.3389/fphar.2019.01196] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Accepted: 09/17/2019] [Indexed: 12/14/2022] Open
Abstract
Although the oral route is the most convenient route for drug administration, there are a number of circumstances where this is not possible from either a clinical or pharmaceutical perspective. In these cases, the rectal route may represent a practical alternative and can be used to administer drugs for both local and systemic actions. The environment in the rectum is considered relatively constant and stable and has low enzymatic activity in comparison to other sections of the gastrointestinal tract. In addition, drugs can partially bypass the liver following systemic absorption, which reduces the hepatic first-pass effect. Therefore, rectal drug delivery can provide significant local and systemic levels for various drugs, despite the relatively small surface area of the rectal mucosa. Further development and optimization of rectal drug formulations have led to improvements in drug bioavailability, formulation retention, and drug release kinetics. However, despite the pharmaceutical advances in rectal drug delivery, very few of them have translated to the clinical phase. This review will address the physiological and pharmaceutical considerations influencing rectal drug delivery as well as the conventional and novel drug delivery approaches. The translational challenges and development aspects of novel formulations will also be discussed.
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Affiliation(s)
- Susan Hua
- Therapeutic Targeting Research Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia
- Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
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Anaya Castro MA, Alric I, Brouillet F, Peydecastaing J, Fullana SG, Durrieu V. Spray-Dried Succinylated Soy Protein Microparticles for Oral Ibuprofen Delivery. AAPS PharmSciTech 2019; 20:79. [PMID: 30635750 DOI: 10.1208/s12249-018-1250-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Accepted: 11/13/2018] [Indexed: 02/01/2023] Open
Abstract
The potential value of succinylated soy protein (SPS) as a wall material for the encapsulation of ibuprofen (IBU), a model hydrophobic drug, by spray-drying was investigated. A succinylation rate of 93% was obtained for soy protein isolate, with a molar ratio of 1/1.5 (NH2/succinic anhydride). The solubility profile at 37°C showed that this chemical modification decreased the solubility of the protein below its isoelectric point, whereas solubility increased in alkaline conditions. Various SPS/IBU ratios (90/10, 80/20, and 60/40) were studied and compared with the same ratio of soy protein isolate (SPI/IBU). High encapsulation efficiency was achieved (91-95%). Microparticles were spherical and between 4 and 8 μm in diameter. The spray-drying of protein/IBU solutions appeared to be beneficial, as it resulted in an amorphous solid dispersion of IBU within the microparticles, coupled with an increase in the thermal stability of IBU. In vitro release was evaluated in acidic (pH 1.2 in the presence of pepsin) and neutral (pH 6.8) conditions similar to those in the gastrointestinal (GI) tract. IBU was released significantly more slowly at pH 1.2, for both proteins. However, this slowing was particularly marked for SPS, for which rapid (within 2 h) and complete release was observed at pH 6.8. These results validate the hypothesis that SPS is suitable for use as a coating material for hydrophobic active pharmaceutical ingredients (APIs) due to its pH sensitivity, which should delay IBU release in the gastrointestinal tract.
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Melo M, Nunes R, Sarmento B, das Neves J. Colorectal distribution and retention of polymeric nanoparticles following incorporation into a thermosensitive enema. Biomater Sci 2019; 7:3801-3811. [DOI: 10.1039/c9bm00759h] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The incorporation of nanoparticles into a thermosensitive enema enhances colorectal distribution and retention.
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Affiliation(s)
- Mélanie Melo
- i3S – Instituto de Investigação e Inovação em Saúde
- Universidade do Porto
- Porto
- Portugal
- INEB – Instituto de Engenharia Biomédica
| | - Rute Nunes
- i3S – Instituto de Investigação e Inovação em Saúde
- Universidade do Porto
- Porto
- Portugal
- INEB – Instituto de Engenharia Biomédica
| | - Bruno Sarmento
- i3S – Instituto de Investigação e Inovação em Saúde
- Universidade do Porto
- Porto
- Portugal
- INEB – Instituto de Engenharia Biomédica
| | - José das Neves
- i3S – Instituto de Investigação e Inovação em Saúde
- Universidade do Porto
- Porto
- Portugal
- INEB – Instituto de Engenharia Biomédica
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Giuliano E, Paolino D, Fresta M, Cosco D. Mucosal Applications of Poloxamer 407-Based Hydrogels: An Overview. Pharmaceutics 2018; 10:pharmaceutics10030159. [PMID: 30213143 PMCID: PMC6161217 DOI: 10.3390/pharmaceutics10030159] [Citation(s) in RCA: 201] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 08/23/2018] [Accepted: 09/10/2018] [Indexed: 02/07/2023] Open
Abstract
Poloxamer 407, also known by the trademark Pluronic® F127, is a water-soluble, non-ionic triblock copolymer that is made up of a hydrophobic residue of polyoxypropylene (POP) between the two hydrophilic units of polyoxyethylene (POE). Poloxamer 407-based hydrogels exhibit an interesting reversible thermal characteristic. That is, they are liquid at room temperature, but they assume a gel form when administered at body temperature, which makes them attractive candidates as pharmaceutical drug carriers. These systems have been widely investigated in the development of mucoadhesive formulations because they do not irritate the mucosal membranes. Based on these mucoadhesive properties, a simple administration into a specific compartment should maintain the required drug concentration in situ for a prolonged period of time, decreasing the necessary dosages and side effects. Their main limitations are their modest mechanical strength and, notwithstanding their bioadhesive properties, their tendency to succumb to rapid elimination in physiological media. Various technological approaches have been investigated in the attempt to modulate these properties. This review focuses on the application of poloxamer 407-based hydrogels for mucosal drug delivery with particular attention being paid to the latest published works.
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Affiliation(s)
- Elena Giuliano
- Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, I-88100 Catanzaro, Italy.
| | - Donatella Paolino
- Department of Experimental and Clinical Medicine, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, I-88100 Catanzaro, Italy.
| | - Massimo Fresta
- Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, I-88100 Catanzaro, Italy.
| | - Donato Cosco
- Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, I-88100 Catanzaro, Italy.
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Zahir-Jouzdani F, Wolf JD, Atyabi F, Bernkop-Schnürch A. In situ gelling and mucoadhesive polymers: why do they need each other? Expert Opin Drug Deliv 2018; 15:1007-1019. [PMID: 30173567 DOI: 10.1080/17425247.2018.1517741] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
INTRODUCTION Mucosal drug delivery is an attractive route of administration, particularly in overcoming deficits of conventional dosage forms including high first-pass metabolism and poor bioavailability. Fast drainage from the target mucosa, however, represents a major limitation as it prevents sufficient drug absorption. In order to address these problems, mucoadhesive in situ gelling drug delivery systems have been investigated as they facilitate easy application in combination with a longer residence time at the administration site resulting in more desirable therapeutic effects. AREAS COVERED The present review evaluates the importance of the combination of mucoadhesive and in situ gelling polymers along with mechanisms of in situ gelation and mucoadhesion. In addition, an overview about recent applications in mucosal drug delivery is provided. EXPERT OPINION In situ gelling and mucoadhesive polymers proved to be essential excipients in order to prolong the mucosal residence time of drug delivery systems. Due to this prolonged residence time both local and systemic therapeutic efficacy of numerous drugs can be substantially improved. Depending on the site of administration and the incorporated drug, combinations of different polymers with in situ gelling and mucoadhesive properties are needed to keep the delivery system as long as feasible at the target site.
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Affiliation(s)
- Forouhe Zahir-Jouzdani
- a Department of Pharmaceutical Technology , Institute of Pharmacy, University of Innsbruck , Innsbruck , Austria.,b Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran
| | - Julian Dominik Wolf
- a Department of Pharmaceutical Technology , Institute of Pharmacy, University of Innsbruck , Innsbruck , Austria.,c Thiomatrix Forschungs- und Beratungs GmbH, Research Center Innsbruck , Trientlgasse, Innsbruck , Austria
| | - Fatemeh Atyabi
- b Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran
| | - Andreas Bernkop-Schnürch
- a Department of Pharmaceutical Technology , Institute of Pharmacy, University of Innsbruck , Innsbruck , Austria
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Anaya Castro MA, Alric I, Brouillet F, Peydecastaing J, Fullana SG, Durrieu V. Soy Protein Microparticles for Enhanced Oral Ibuprofen Delivery: Preparation, Characterization, and In Vitro Release Evaluation. AAPS PharmSciTech 2018; 19:1124-1132. [PMID: 29214609 DOI: 10.1208/s12249-017-0928-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Accepted: 11/25/2017] [Indexed: 11/30/2022] Open
Abstract
The objective of this work was to evaluate soy protein isolate (SPI) and acylated soy protein (SPA) as spray-drying encapsulation carriers for oral pharmaceutical applications. SPI acylation was performed by the Schotten-Baumann reaction. SPA, with an acylation rate of 41%, displayed a decrease in solubility in acidic conditions, whereas its solubility was unaffected by basic conditions. The drug encapsulation capacities of both SPI and SPA were tested with ibuprofen (IBU) as a model poorly soluble drug. IBU-SPI and IBU-SPA particles were obtained by spray-drying under eco-friendly conditions. Yields of 70 to 87% and microencapsulation efficiencies exceeding 80% were attained for an IBU content of 20 to 40% w/w, confirming the excellent microencapsulation properties of SPI and the suitability of the chemical modification. The in vitro release kinetics of IBU were studied in simulated gastrointestinal conditions (pH 1.2 and pH 6.8, 37°C). pH-sensitive release patterns were observed, with an optimized low rate of release in simulated gastric fluid for SPA formulations, and a rapid and complete release in simulated intestinal fluid for both formulations, due to the optimal pattern of pH-dependent solubility for SPA and the molecular dispersion of IBU in soy protein. These results demonstrate that SPI and SPA are relevant for the development of pH-sensitive drug delivery systems for the oral route.
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