Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China; Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China.
Int J Pharm. 2015 Mar 1;480(1-2):128-36. doi: 10.1016/j.ijpharm.2015.01.032. Epub 2015 Jan 20.
This study was aimed to design a liposomal based ion-sensitive in situ ophthalmic delivery system of timolol maleate (TM). The TM liposome was produced by the reverse evaporation technique coupled with pH-gradients method (REVPR), and then was incorporated into deacetylated gellan gum gels. The TM liposome was demonstrated to be a round and uniform shape in TEM pictures. Compared with the TM eye drops, the TM liposome produced a 1.93 folds increase in apparent permeability coefficients (Papp), resulting in a significant increase of the corneal penetration. The TM-loaded liposome incorporated ion sensitive in situ gels (TM L-ISG) showed longer retention time on corneal surface compared with the eye drops using gamma scintigraphy technology. Draize testing showed that TM L-ISG was non-irritant for ocular tissues. The biggest efficacy of TM L-ISG occurred 30 min after eye drops administration, and efficacy disappeared after 240min. Then, compared with the eye drops, the optimal TM L-ISG could quickly reduce the intraocular pressure and the effective time was significantly longer (P≤0.05). These results indicate that liposome incorporated ion sensitive in situ gels have a potential ability for the opthalmic delivery.
本研究旨在设计马来酸噻吗洛尔（TM）的基于脂质体的离子敏感型眼内原位递药系统。TM 脂质体通过反蒸发技术与 pH 梯度法（REVPR）联合生产，然后被掺入去乙酰化结冷胶凝胶中。TEM 图片显示 TM 脂质体为圆形且均匀的形状。与 TM 滴眼液相比，TM 脂质体使表观渗透系数（Papp）增加了 1.93 倍，导致角膜穿透性显著增加。用γ闪烁成像技术显示，载 TM 的脂质体结合离子敏感原位凝胶（TM L-ISG）在角膜表面的滞留时间比滴眼液更长。Drazce 测试表明，TM L-ISG 对眼部组织无刺激性。TM L-ISG 的最大疗效在滴眼后 30 分钟出现，240 分钟后疗效消失。然后，与滴眼液相比，最佳的 TM L-ISG 可以快速降低眼内压，有效时间明显更长（P≤0.05）。这些结果表明，脂质体结合离子敏感原位凝胶具有用于眼部递药的潜力。
