Abstract：
Delivering medication to the posterior segment of the eye presents a significant challenge. Intravitreal injection has emerged as the preferred method for drug delivery to this area. However, current injectable non-biodegradable implants for fluocinolone acetonide (FA) require surgical removal after prolonged drug release, potentially affecting patient compliance. This study aimed to develop an in-situ forming biodegradable implant (ISFBI) optimal formulation containing PLGA504H and PLGA756S (50:50 w/w%) with the additive NMP solvent. The goal was to achieve slow and controlled release of FA over a two-month period with lower burst release, following a single intravitreal injection. Through morphology, rheology, stability and in-vitro release evaluations, the optimal formulation demonstrated low viscosity (0.12-1.25 Pa. s) and sustained release of FA at a rate of 0.36 µg/day from the third day up to two months. Furthermore, histopathology and in-vivo studies were conducted after intravitreal injection of the optimal formulation in rabbits\' eye. Pharmacokinetic analysis demonstrated mean residence time (MRT) of 20.02 ± 0.6 days, half-life (t1/2) of 18.80 ± 0.4 days, and clearance (Cl) of 0.29 ± 0.03 ml/h for FA in the vitreous humor, indicating sustained and slow absorption of FA by the targeted retinal tissue from vitrea over the two-month period and eliminating through the anterior section of the eye, as revealed by its presence in the aqueous humor. Additionally, FA exhibited no detection in the blood and no evidence of systemic side effects or damage on the retinal layer and other organs. Based on these findings, it can be concluded that in-situ forming injectable biodegradable PLGA implants can show promise as a long-acting and controlled-release system for intraocular drug delivery.
摘要：
将药物递送到眼睛的后段提出了重大挑战。玻璃体内注射已成为将药物递送到该区域的优选方法。然而,目前用于氟轻松（FA）的可注射非生物降解植入物需要在延长药物释放后进行手术切除，可能影响患者的依从性。本研究旨在开发含有PLGA504H和PLGA756S(50:50w/w%)以及添加剂NMP溶剂的原位形成可生物降解植入物(ISFBI)最佳配方。目标是在两个月的时间内实现FA的缓慢和受控释放，在单次玻璃体内注射后。通过形态学，流变学,稳定性和体外释放度评价，最佳配方显示出低粘度（0.12-1.25Pa。s）和从第三天到两个月以0.36µg/天的速率持续释放FA。此外，在兔眼中玻璃体内注射最佳制剂后进行组织病理学和体内研究。药代动力学分析显示平均停留时间（MRT）为20.02±0.6天，半衰期（t1/2）为18.80±0.4天，玻璃体液中FA的清除率（Cl）为0.29±0.03ml/h，表明在两个月的时间内，目标视网膜组织从玻璃体中持续和缓慢吸收FA，并通过眼前部分消除FA，正如它在房水中的存在所揭示的。此外,在血液中未检测到FA，也没有证据表明对视网膜层和其他器官有全身副作用或损害。基于这些发现,可以得出结论，原位形成可注射的可生物降解PLGA植入物可以显示出有望作为一种长效和控释系统用于眼内药物递送。
