Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
Liaoning Heshi Medical College, Sishui Street 66, Shenyang 110163, PR China.
Colloids Surf B Biointerfaces. 2017 Dec 1;160:305-314. doi: 10.1016/j.colsurfb.2017.08.037. Epub 2017 Aug 25.
The purpose of the study was to design a novel octa-arginine (R8) modified lipid emulsion (LE) system for the ocular delivery of the lipophilic drug disulfiram (DSF). The influence of the particle size of the lipid emulsions and the presence of R8 on corneal permeation was studied. DSF-loaded lipid emulsions with different particle sizes (DSF-LE1, DSF-LE2, DSF-LE3) and DSF-loaded lipid emulsions modified with R8 (DSF-LE1-R8 and DSF-LE2-R8) were prepared. The Zeta potential of the lipid emulsions was changed from negative to a positive value after modification of R8. The mucoadhesion of different preparations was investigated, and DSF-LE1-R8 was found to produce the strongest mucoadhesion. The in vitro corneal penetration study and in vivo ocular distribution study showed that the R8 modified lipid emulsion (DSF-LE1-R8) with a nano particle size, exhibited the highest permeability and the largest amount of DDC distributed in ocular issues. Coumarin-6 labelled LE1-R8 displayed more homogeneous fluorescence with the deeper penetration into the cornea compared with other preparations at various times. Confocal laser scanning microscopy showed that, in addition to paracellular routes, LE-R8 could also transport across the corneal epithelium by transcellular routes as a result of increased uptake due to the R8 modification. Furthermore, the anti-cataract effect was evaluated and it was found that DSF-LE1-R8 exhibited a marked anti-cataract effect. Therefore, the lipid emulsions with nano-sized particles and modification of R8 were proposed as a potential ocular delivery system to improve the corneal penetration and ocular delivery of DSF.
本研究旨在设计一种新型八精氨酸（R8）修饰的脂质乳剂（LE）系统，用于脂溶性药物双硫仑（DSF）的眼部递药。研究了脂质乳剂的粒径和 R8 的存在对角膜渗透的影响。制备了不同粒径的载有 DSF 的脂质乳剂（DSF-LE1、DSF-LE2、DSF-LE3）和 R8 修饰的载有 DSF 的脂质乳剂（DSF-LE1-R8 和 DSF-LE2-R8）。R8 修饰后，脂质乳剂的 Zeta 电位从负值变为正值。考察了不同制剂的粘膜黏附性，发现 DSF-LE1-R8 产生最强的粘膜黏附性。体外角膜渗透研究和体内眼内分布研究表明，具有纳米粒径的 R8 修饰脂质乳剂（DSF-LE1-R8）表现出最高的渗透性和最大量的 DDC 分布在眼部问题中。香豆素-6 标记的 LE1-R8 在不同时间显示出更均匀的荧光，并且比其他制剂更深地渗透到角膜中。共聚焦激光扫描显微镜显示，LE-R8 除了通过细胞旁途径外，还可以通过跨细胞途径转运，这是由于 R8 修饰导致摄取增加。此外，还评价了抗白内障作用，发现 DSF-LE1-R8 表现出明显的抗白内障作用。因此，提出了具有纳米粒径和 R8 修饰的脂质乳剂作为一种潜在的眼部递药系统，以提高 DSF 的角膜穿透和眼部递药。
