Biomimetic thiamine- and niacin-decorated liposomes for enhanced oral delivery of insulin

作     者：Haisheng He Yi Lu Jianping Qi Weili Zhao Xiaochun Dong Wei Wu 

作者机构：Key Laboratory of Smart Drug Delivery of MOE and PLA School of Pharmacy Fudan University 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2018年第8卷第1期

页      面：97-105页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 100602[医学-中西医结合临床] 

基　　金：financially supported by Shanghai Commission of Science and Technology (15ZR1403000) National Natural Science Foundation of China (81573363, 81690263, and 21372063) 

主　　题：Liposomes Vitamin Thiamine Niacin Insulin Biomimetic Oral Drug delivery 

摘      要：Biomimetic nanocarriers are emerging as efficient vehicles to facilitate dietary absorption of biomacromolecules. In this study, two vitamins, thiamine and niacin, are employed to decorate liposomes loaded with insulin, thus facilitating oral absorption via vitamin ligand–receptor interactions. Both vitamins are conjugated with stearamine, which works to anchor the ligands to the surface of liposomes.Liposomes prepared under optimum conditions have a mean particle size of 125–150 nm and an insulin entrapment efficiency of approximately 30%–36%. Encapsulation into liposomes helps to stabilize insulin due to improved resistance against enzymatic disruption, with 60% and 80% of the insulin left after 4 h when incubated in simulated gastric and intestinal fluids, respectively, whereas non-encapsulated insulin is broken down completely at 0.5 h. Preservation of insulin bioactivity against preparative stresses is validated by intra-peritoneal injection of insulin after release from various liposomes using the surfactant Triton X-100. In a diabetic rat model chemically induced by streptozotocin, both thiamine-and niacindecorated liposomes showed a comparable and sustained mild hypoglycemic effect. The superiority of decorated liposomes over conventional liposomes highlights the contribution of vitamin ligands. It is concluded that decoration of liposomes with thiamine or niacin facilitates interactions with gastrointestinal vitamin receptors and thereby facilitates oral absorption of insulin-loaded liposomes.