Development of Injectable Biodegradable In-Situ Forming Drug Delivery System for Glaucoma Therapy

• Main Authors: Li Jyuan Luo, 羅麗娟
• Other Authors: J. Y. Lai
• Format: Others
• Language: en_US
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/ud488e

博士 === 長庚大學 === 化工與材料工程學系 === 106 === Glaucoma is the second worldwide leading cause of blindness. Eye drops are frequently used to administer medication for ocular disease treatment. However, the main challenges with this type of dosage form include short precorneal residence time, poor corneal penetration, and low ocular bioavailability. Hence, to improve ocular bioavailability and pharmacological response, we used intracameral administration of drug containing thermo-sensitive biodegradable copolymer for glaucoma therapy. In chapter 2 and 3, these charpters focused on “Extended Drug Delivery System” and “Antioxidation Functionalization Biodegrable Hydrogel”. In chapter 2.1, three different Bloom numbers of gelatins were used to synthesize thermosensitive hydrogels and recognize effects on pharmacological treatment. In chapter 2.2, four kinds of alkyl chain length of monothiol-terminated alkyl carboxylic acids were used to synthesized various carboxylic end-capped PNIPAAm samples. In addition, the glaucoma is considered to be a chronic disease requiring lifetime medical therapy and it often takes years to monitor disease progression. In chapter 2.3 and 2.4, the polysaccharide-based drug delivery systems with various deacetylation degree were developed for extended drug release prolife and improved delivery performance. The result of the first stage, the higher Bloom number and longer alkyl chain length can enhance antiglaucoma efficacy and therapeutic effectiveness. Furthermore, the chitosan-based thermogels can be higher potentially utilized as ophthalmic biomaterial carriers for extended drug release and improved delivery performance. On the other hand, hypertension and oxidative stress are known to be involved in glaucomatous development and progression. In chapter 3.1, antioxidant gallic acid functionalized thermosensitive biodegradable hydrogel was developed. In chapter 3.2, we have explored the effect of redox reaction time of hydroxyl radicals and the amount of gallic acid grafted onto carrier. Given that ocular hypertension and oxidative stress disrupts axonal transport of retinal ganglion cells and results in cell death. In chatper 3.3, we further discussed the effect of redox reaction temperature of hydroxyl radicals and examined in vivo pharmacological efficacy of drug containing carriers in glaucomatous rabbits. The result of the second stage, a series of polymers were synthesized via adjusting redox reaction time and temperature. In chapter 4, the therapeutic action of epigallocatechin gallate is linked to its strong bioactivities (antioxidant and anti-inflammation capacity), which may be helpful in treating preservative (i.e., benzalkonium chloride)-induced rabbit dry eye. Given that biodegradable in situ gelling delivery systems may have potential applications in the design of ophthalmic pharmaceutical formulations, this study, for the first time, aims to develop carriers for topical antioxidant molecular administration in the treatment of dry eye disease. Our findings suggest that carrier is responsible for enhanced pharmacological efficacy of topically instilled epigallocatechin gallate, thereby demonstrating the benefits of using biodegradable in situ gelling delivery system to overcome the drawbacks of limited dry eye relief associated with eye drop dosage form. In the present data, we have demonstrated that the ophthalmic biomaterial carriers for extended drug release can be synthesized by adjusting the factors (Bloom number/alkyl chain length/polymer backbone/ deacetylation degree) to optimize the delivery performance. On the other hand, the redox reaction time/temperature-mediated gallic acid grafting amount is a key parameter in the development of antioxidant drug delivery systems for protection against retinal injury, suggesting the benefits of biomaterials to prevent oucalar disease development. Furthermore, the information about the effect of single epigallocatechin gallate drop administration using biodegradable in situ gelling carrier on dry eye relief presents an opportunity for further development of pharmacological interventions. Overall, this obtained data will be of high clinical significance and contribute to the knowledge of materials for management of ocular diseases.