PLGA公司
甲氨蝶呤
药代动力学
人工晶状体
药理学
药品
纤维连接蛋白
化学
眼科
生物医学工程
医学
细胞外基质
外科
生物化学
体外
作者
Clarissa Bill,Stefan Kassumeh,Christina Hilterhaus,Natalie Tersi,Arne Jorma Speidel,Andreas Ohlmann,Siegfried Priglinger,Claudia Priglinger,Armin Wolf,Christian Wertheimer
标识
DOI:10.1177/11206721241239717
摘要
Introduction The intraocular lens (IOL) can be used as a slow-release drug carrier in cataract surgery to alleviate posterior capsular opacification (PCO). The following is a systematic development of an IOL using methotrexate and the solvent casting process with poly (lactic-co-glycolic acid) (PLGA) as a carrier polymer. Methods Different solvents for PLGA and methotrexate were tested for dissolution properties and possible damage to the IOL. The required biological concentration of methotrexate was determined in human capsular bags implanted with an IOL. To detect fibrosis, α-SMA, f-actin, and fibronectin were labelled by immunofluorescence staining. Cell proliferation and extracellular matrix contraction were observed in a lens epithelial cell line (FHL-124). Finally, the IOL was designed, and an ocular pharmacokinetic model was used to measure drug release. Results Solvent mixtures were found to allow coating of the IOL with drug and PLGA without damaging it. PCO in the capsular bag model was inhibited above 1 μM methotrexate ( p = 0.02). Proliferation in FHL-124 was significantly reduced above a concentration of 10 nM ( p = 0.04) and matrix contraction at 100 nM ( p = 0.02). The release profile showed a steady state within therapeutic range. Conclusion After determination of the required physicochemical manufacturing conditions, a drug releasing IOL was designed. A favourable release profile in an ocular pharmacokinetics model could be shown.
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