製備新穎智慧型水膠及其眼部給藥抑制異常血管增生之應用

蔣永生

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製備新穎智慧型水膠及其眼部給藥抑制異常血管增生之應用

Smart Hydrogels As an Intraocular Sustained-Release Materials for Biologics

蔣永生 , Masters　　Advisor：鄭文桐　　Co-advisor ：薛敬和

繁體中文

癌思停；聚(2-乙基-2-咢唑啉) ；聚己內酯團聯共聚物；溫度敏感性；生物可降解性；可注射型緩釋藥物載體；異常血管增生；視網膜電生理； Avastin® ； Biodegradable ； Block copolymers ； Electrophysiology ； Hydrogels ； Injectable sustained-release ocular carrier ； Neovascularization ； Poly(2-ethyl-2-oxazoline) ； Poly(ε-caprolactone) ； Thermo-sensitive.

Abstract │ Reference (51) │ Altmetrics

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A novel biodegradable and thermo-sensitive block copolymers consisting of poly(2-ethyl-2-oxazoline) and poly(ε-caprolactone) (PEOz-PCL-PEOz, ECE) were synthesized, and the triblock copolymers solution have shown a reversible sol (room temperature)-gel (physiological temperature) phase transition by temperature change. The phase-transition character could be employed as an injectable, sustained-release drug delivery carrier for biologics, which are commonly constructed as fragile proteins or peptides. The chemical structures and molecular characteristics of the triblock copolymers were identified by 1H NMR and FTIR. The biodegradation rate of ECE was studied in balance salt solution (BSS), which is the standard salt solution for intraocular surgeries, at 37℃ for 3 months by GPC, and its porosity were obtained with different time periods by SEM. The result showed that molecular weight of ECE was hardly changed for 2 months, but the crosslinking of PEOz was gradually dissolved, the pores of the hydrogels became more numerous and extension. Pluronic F-127 and Matrigel&reg;, which were also used as the in-situ gel-forming carriers, were studied simultaneously to compare. The drug release profiles of these hydrogels were obtained using an anti-body Bevacizumab (Avastin&reg;) , which has been widely used intraocularly for neovascularization diseases, as biologics by ELISA kit. The result showed that the release of Bevacizumab from ECE had been sustained and extended for one month than from Pluronic F-127 and Matrigel&reg;. The in vitro cytotoxicity assay, using Human RPE cell line (ARPE-19 cell, a cultivable human retinal cell line), showed the ECE had good biocompatibility within 24 hours by flow cytometry. We injected the three kinds of hydrogels into vitreous of rabbits eyes. The electrophysiology after two month showed comparable waveforms between study eye and control eye in ECE but Pluronic F-127 and Matrigel&reg;. The ECE hydrogels may have a lower retinal cytotoxicity in vivo than Pluronic F-127 and Matrigel&reg;, and may have a better potential than Pluronic F-127 and Matrigel&reg; as an intraocular drug carrier.

Reference ( 51 ) 〈TOP〉

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