Abdelkader Hamdy, Wertheim David, Pierscionek Barbara, Alany Raid G
Pharmaceutics Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Deraya University, New Minia City, Minia 61519, Egypt.
Pharmaceutics. 2020 Nov 28;12(12):1158. doi: 10.3390/pharmaceutics12121158.
The search for an ocular drug delivery system that could provide long-acting effects without a detriment to the anatomy and physiology of the eye remains a challenge. Polyphenolic compounds (curcumin in particular) have recently gained popularity due to their powerful antioxidant properties; yet curcumin suffers poor stability and water solubility. A conventional eye drop formulation of curcumin in the form of a suspension is likely to suffer a short duration of action requiring multiple instillations. On the other hand, polymeric in-situ gelling inserts offer the prospect of overcoming these limitations. The aim of this study was to prepare, characterize and evaluate in vivo, polymeric, in-situ gelling and mucoadhesive inserts for ocular surface delivery of curcumin. Different types and ratios of biocompatible polymers (HPMC, CMC, PL 127 and PVA) and three plasticizers along with the solvent casting method were adopted to prepare curcumin inserts. The inserts were investigated for their physicochemical characteristics, applicability, and suitability of use for potential placement on the ocular surface. The prepared inserts revealed that curcumin was mainly dispersed in the molecular form. Insert surfaces remained smooth and uniform without cracks appearing during preparation and thereafter. Improved mechanical and mucoadhesive properties, enhanced in vitro release (7.5- to 9-fold increases in RRT min) and transcorneal permeation (5.4- to 8.86-fold increases in Papp) of curcumin was achieved by selected in-situ gelling inserts compared to a control curcumin suspension. The developed inserts demonstrated acceptable ocular tolerability, enhanced corneal permeability, and sustained release of curcumin along with retention of insert formulation F7 on the ocular surface for at least two-hours. This insert provides a viable alternative to conventional eye drop formulations of curcumin.
寻找一种能提供长效作用且不损害眼睛解剖结构和生理功能的眼部给药系统仍然是一项挑战。多酚类化合物（尤其是姜黄素）因其强大的抗氧化特性最近受到关注；然而，姜黄素稳定性差且水溶性不佳。以悬浮液形式存在的传统姜黄素滴眼液制剂作用时间可能较短，需要多次滴注。另一方面，聚合物原位凝胶插入剂有望克服这些限制。本研究的目的是制备、表征并在体内评估用于眼部表面递送姜黄素的聚合物原位凝胶和粘膜粘附插入剂。采用不同类型和比例的生物相容性聚合物（羟丙基甲基纤维素、羧甲基纤维素、泊洛沙姆127和聚乙烯醇）以及三种增塑剂，并结合溶剂浇铸法制备姜黄素插入剂。对这些插入剂的物理化学特性、适用性以及在眼部表面潜在放置的适用性进行了研究。制备的插入剂显示姜黄素主要以分子形式分散。插入剂表面保持光滑均匀，在制备过程中及之后均未出现裂缝。与对照姜黄素悬浮液相比，通过选择的原位凝胶插入剂实现了姜黄素改善的机械和粘膜粘附性能、增强的体外释放（相对释放时间分钟增加7.5至9倍）和角膜渗透（表观渗透系数增加5.4至8.86倍）。所开发的插入剂表现出可接受的眼部耐受性、增强的角膜通透性以及姜黄素的持续释放，并且插入剂制剂F7在眼部表面保留至少两小时。这种插入剂为传统姜黄素滴眼液制剂提供了一种可行的替代方案。
