State Key Laboratory of Biotherapy/Geriatrics and Cancer Center, West China Hospital, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China.
School of Nanotechnology Engineering, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
Int J Pharm. 2018 Dec 20;553(1-2):21-28. doi: 10.1016/j.ijpharm.2018.10.033. Epub 2018 Oct 11.
The aim of this study is to investigate the potential of D-alpha-tocopheryl poly (ethylene glycol 1000) succinate (TPGS) modified nanoliposomes as an ophthalmic delivery system of brinzolamide (Brz) for glaucoma treatment. The Brz loaded nanoliposomes containing TPGS (T-LPs/Brz) were firstly developed by a thin-film dispersion method. The average particle size was 96.87 ± 4.43 nm. The entrapment efficiency of the Brz was 95.41 ± 3.03% and the drug loading was 4.00 ± 0.13%. T-LPs/Brz exhibited obvious sustained release of Brz; in stark contrast to the normal liposomes of Brz (LPs/Brz) and the commercial formulation AZOPT® (Brz ophthalmic suspension, Brz-Sus). Enhanced trans-corneal transport of Brz was achieved with T-LPs/Brz. Compared with both Brz-Sus and LPs/Brz, the apparent permeability coefficient (P) of T-LPs/Brz was 10.2 folds and 1.38 folds higher, respectively. Moreover, T-LPs/Brz extended the cornea residence of Brz. White New Zealand rabbits treated with T-LPs/Brz had 3.18 folds and 1.57 folds Brz concentration 2 h after treatment than Brz-Sus and LPs/Brz, respectively. Further pharmacodynamic studies showed that T-LPs/Brz maintained an effective intraocular pressure (IOP) reduction from 3 h to 11 h after administration, while Brz-Sus and LPs/Brz presented effective IOP decreases from 3 h to 6 h and 3 h to 8 h respectively. The preliminary safety evaluation demonstrated that T-LPs/Brz had no significant side effects; specifically, no cornea damage and eye irritation. All the results indicated that TPGS modified nanoliposomes were a promising ocular delivery carriers for Brz to treat glaucoma. As such, T-LPs/Brz might be worthy of further translational study.
本研究旨在探讨 D-α-生育酚聚乙二醇 1000 琥珀酸酯（TPGS）修饰的纳米脂质体作为治疗青光眼的布林佐胺（Brz）眼部递药系统的潜力。采用薄膜分散法首次制备了含有 TPGS 的 Brz 负载纳米脂质体（T-LPs/Brz）。平均粒径为 96.87±4.43nm。Brz 的包封率为 95.41±3.03%，载药量为 4.00±0.13%。T-LPs/Brz 表现出明显的 Brz 持续释放；与 Brz 的普通脂质体（LPs/Brz）和商业制剂 AZOPT®（Brz 眼用混悬剂，Brz-Sus）形成鲜明对比。T-LPs/Brz 增强了 Brz 的经角膜转运。与 Brz-Sus 和 LPs/Brz 相比，T-LPs/Brz 的表观渗透系数（P）分别提高了 10.2 倍和 1.38 倍。此外，T-LPs/Brz 延长了 Brz 在角膜中的滞留时间。经 T-LPs/Brz 处理的新西兰白兔在治疗后 2 小时的 Brz 浓度分别是 Brz-Sus 和 LPs/Brz 的 3.18 倍和 1.57 倍。进一步的药效学研究表明，T-LPs/Brz 在给药后 3 至 11 小时内保持有效的眼压（IOP）降低，而 Brz-Sus 和 LPs/Brz 在给药后 3 至 6 小时和 3 至 8 小时内呈现有效的 IOP 降低。初步的安全性评价表明，T-LPs/Brz 没有明显的副作用；具体来说，没有角膜损伤和眼部刺激。所有结果表明，TPGS 修饰的纳米脂质体是一种有前途的 Brz 眼部递药载体，可用于治疗青光眼。因此，T-LPs/Brz 可能值得进一步的转化研究。
