Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Department of Medical Physiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Drug Deliv. 2022 Dec;29(1):1150-1163. doi: 10.1080/10717544.2022.2058648.
Glaucoma is one of the leading causes of blindness. Therapies available suffer from several drawbacks including low bioavailability, repeated administration and poor patient compliance with adverse effects thereafter. In this study, bovine serum albumin nanoparticles (BSA-NPs) coated with chitosan(CS) were developed for the topical delivery of tetrandrine (TET) for glaucoma management. Optimized nanoparticles were prepared by desolvation. pH, BSA, CS and cross-linking agent concentrations effects on BSA-NPs colloidal properties were investigated. CS-BSA-NPs with particle size 237.9 nm and zeta potential 24 mV was selected for further evaluation. EE% exceeded 95% with sustained release profile. In vitro mucoadhesion was evaluated based on changes in viscosity and zeta potential upon incubation with mucin. transcorneal permeation was significantly enhanced for CS coated formulation. cell culture studies on corneal stromal fibroblasts revealed NPs biocompatibility with enhanced cellular uptake and improved antioxidant and anti-proliferative properties for the CS-coated formulation. Moreover, BSA-NPs were nonirritant as shown by HET-CAM test. Also, bioavailability in rabbit aqueous humor showed 2-fold increase for CS-TET-BSA-NPs compared to TET with a sustained reduction in intraocular pressure in a rabbit glaucoma model. Overall, results suggest CS-BSA-NPs as a promising platform for topical ocular TET delivery in the management of glaucoma.
青光眼是导致失明的主要原因之一。现有的治疗方法存在多种缺陷，包括生物利用度低、需要重复给药以及患者因不良反应而依从性差。在这项研究中，开发了壳聚糖（CS）包覆的牛血清白蛋白纳米粒（BSA-NPs），用于局部递送用于治疗青光眼的汉防己甲素（TET）。通过去溶剂化法制备优化的纳米粒。研究了 pH 值、BSA、CS 和交联剂浓度对 BSA-NPs 胶体性质的影响。选择粒径为 237.9nm 和 Zeta 电位为 24mV 的 CS-BSA-NPs 进行进一步评估。EE%超过 95%，具有持续释放特性。根据与粘蛋白孵育时粘度和 Zeta 电位的变化，评估了体外粘膜粘附性。对于包被的制剂，角膜穿透性显著增强。角膜基质成纤维细胞的细胞培养研究表明，与未包被的制剂相比，纳米粒具有生物相容性，并且细胞摄取增强，CS 包被的制剂具有更好的抗氧化和抗增殖特性。此外，BSA-NPs 通过 HET-CAM 试验显示是非刺激性的。在兔房水生物利用度研究中，与 TET 相比，CS-TET-BSA-NPs 的生物利用度增加了 2 倍，并且在兔青光眼模型中眼压持续降低。总之，结果表明 CS-BSA-NPs 是一种有前途的局部眼部 TET 递送平台，可用于治疗青光眼。
