Alvarez-Rivera Fernando, Fernández-Villanueva David, Concheiro Angel, Alvarez-Lorenzo Carmen
Departamento de Farmacia y Tecnología Farmacéutica (Group GI-1645), Facultad de Farmacia, Universidade de Santiago de Compostela, Santiago de Compostela 15782, Spain.
Departamento de Farmacia y Tecnología Farmacéutica (Group GI-1645), Facultad de Farmacia, Universidade de Santiago de Compostela, Santiago de Compostela 15782, Spain.
J Pharm Sci. 2016 Sep;105(9):2855-2863. doi: 10.1016/j.xphs.2016.03.006. Epub 2016 Apr 19.
α-Lipoic acid (ALA) is a powerful antioxidant valuable for prevention and treatment of ophthalmic complications such as diabetic keratopathy and retinopathy. The aim of this work was to develop micelle-based formulations that can enhance the solubility, stability, and corneal permeability of ALA. Compared to a conventional surfactant (sodium dioctylsulfosuccinate), Soluplus(®) (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol copolymer) led to smaller micelles (70-80 vs. 240-528 nm) with improved ability to solubilize ALA, maintaining ocular compatibility (Hens Egg Test on the Chorio-Allantoic Membrane). Soluplus nanomicelles enhanced more than 10-fold ALA solubility compared to common eye drops and withstood strong dilution in lachrymal fluid, filtration through sterilizing membranes, and freeze-drying. Interestingly, Soluplus nanomicelle formulation prepared with 1 or 2 mM block copolymer concentration exhibited in situ gelling capability and transformed into weak gels at 35°C, which is expected to increase corneal residence time. Bovine corneal permeability revealed that Soluplus nanomicelles notably enhanced ALA accumulation into the cornea as well as flux of drug toward the receptor chamber. Overall, these findings point out Soluplus nanomicelles as suitable carriers of ALA that may exhibit improved performance compared to currently available eye drop solutions.
α-硫辛酸（ALA）是一种强大的抗氧化剂，对预防和治疗糖尿病性角膜病变和视网膜病变等眼科并发症具有重要价值。本研究的目的是开发基于胶束的制剂，以提高ALA的溶解度、稳定性和角膜通透性。与传统表面活性剂（二辛基磺基琥珀酸钠）相比，Soluplus®（聚乙烯己内酰胺-聚醋酸乙烯酯-聚乙二醇共聚物）形成的胶束更小（70-80对240-528纳米），具有更好的溶解ALA的能力，并保持眼部相容性（鸡胚绒毛尿囊膜试验）。与普通滴眼液相比，Soluplus纳米胶束使ALA的溶解度提高了10倍以上，并且能够耐受泪液中的强烈稀释、通过除菌膜过滤和冷冻干燥。有趣的是，用1或2 mM嵌段共聚物浓度制备的Soluplus纳米胶束制剂具有原位凝胶化能力，并在35°C时转变为弱凝胶，这有望增加角膜停留时间。牛角膜通透性研究表明，Soluplus纳米胶束显著增强了ALA在角膜中的蓄积以及药物向受体腔的通量。总体而言，这些研究结果表明Soluplus纳米胶束是ALA的合适载体，与目前可用的滴眼液相比，可能具有更好的性能。
