Thermo-sensitive gel in glaucoma therapy for enhanced bioavailability: In vitro characterization, in vivo pharmacokinetics and pharmacodynamics study
| Autor: | Jiayuan Huang, Xin Pan, Zhengwei Huang, Ying Huang, Jintian Chen, Yanrong Li, Chuanbin Wu, Youmei Zeng |
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| Rok vydání: | 2018 |
| Předmět: |
Intraocular pressure
genetic structures Drug Evaluation Preclinical Glaucoma Biological Availability Administration Ophthalmic 02 engineering and technology Pharmacology 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Drug Delivery Systems Pharmacokinetics In vivo medicine Animals Tissue Distribution General Pharmacology Toxicology and Pharmaceutics Chemistry Temperature General Medicine Poloxamer 021001 nanoscience & nanotechnology medicine.disease eye diseases Bioavailability Pharmacodynamics Poloxamer 407 Timolol Female sense organs Rabbits 0210 nano-technology Gels medicine.drug |
| Zdroj: | Life sciences. 212 |
| ISSN: | 1879-0631 |
| Popis: | Aims Glaucoma is a chronic ophthalmic disease, which has become one of the leading causes to progressive and irreversible blindness. Current ophthalmic drug delivery to treat glaucoma is mostly eyedrop, whose rapid elimination on corneal surface can lead to poor bioavailability. The present study was aimed to develop a timolol maleate loaded thermo-sensitive gel (TM-TSG) with improved bioavailability to treat glaucoma. Main methods TM-TSG was prepared by homogeneously dispersing 0.3% (w/v) timolol maleate, 24.25% (w/v) poloxamer 407 (P407) and 1.56% (w/v) poloxamer 188 (P188) into phosphate buffer solution (pH = 7.4) and the formulated TM-TSG was characterized. Key findings TM-TSG was stored in liquid form at room temperature (25 °C) and transited to semisolid gel at physiological temperature (32 °C). The rheological property of TM-TSG was in favor of uniform distribution of drug. TM-TSG showed good stability at different conditions including centrifugation, autoclaving and different temperature. In vivo pharmacokinetic studies indicated that TM-TSG could enhance absorption of TM in aqueous humor and improve the ocular bioavailability in comparison of commercial TM eyedrops. In vivo experiment result showed that TM-TSG had greater effect in treating glaucoma than TM eyedrops by sustainably lowering intraocular pressure (IOP) for a week. Moreover, slit lamp test and histopathological analysis demonstrated that TM-TSG had excellent biocompatibility. Significance TM-TSG could be a promising ophthalmic delivery system for glaucoma therapy. |
| Databáze: | OpenAIRE |
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