仿生纳米载体正在成为促进生物大分子饮食吸收的有效载体。在这项研究中,两种维生素,硫胺素和烟酸,用来装饰装有胰岛素的脂质体,从而通过维生素配体-受体相互作用促进口服吸收。两种维生素都与硬脂胺结合,将配体锚定到脂质体表面。在最佳条件下制备的脂质体具有125-150nm的平均粒径和大约30%-36%的胰岛素包封率。封装在脂质体中有助于稳定胰岛素,因为它提高了对酶破坏的抵抗力,在模拟胃液和肠液中孵育4小时后剩下60%和80%的胰岛素,分别,而未包封的胰岛素在0.5h时完全分解。在使用表面活性剂TritonX-100从各种脂质体中释放后,通过腹膜内注射胰岛素来验证对制备应力的胰岛素生物活性的保存。在链脲佐菌素化学诱导的糖尿病大鼠模型中,硫胺素修饰的脂质体和烟酸修饰的脂质体均显示出相当且持续的轻度降血糖作用.修饰脂质体相对于常规脂质体的优越性突出了维生素配体的贡献。结论是,用硫胺素或烟酸修饰脂质体促进与胃肠道维生素受体的相互作用,从而促进胰岛素负载脂质体的口服吸收。
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 niacin-decorated 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.