Cholesterol moieties as building blocks for assembling nanoparticles to achieve effective oral delivery of insulin
Yu Ding, Qiaochu Wang, Guangqu Liu, Yaqian Feng, Wei Zhou
Abstract
could chelate to phosphate groups in the core to bind adjacent phosphate groups and further increased the stability of NPs (CP-Ca NPs). Phospholipid and glycocholate were modified on the surface of CP-Ca NPs to form hydrophilic corona coated CP-Ca NPs (Hc@CP-Ca NPs) and didn't change the structure of CP-Ca NPs. The NPs exhibited high encapsulation efficiency (>95%) and had high stability in the GI tract by reducing insulin release and protecting insulin from enzymatic degradation. Compared to free insulin, Hc@CP-Ca NPs demonstrated 31-fold higher cellular uptake in Caco-2 cells for 1 h incubation. Furthermore, the transepithelial transport efficiency of Hc@CP-Ca NPs was 12-fold higher than that of free insulin. Moreover, CP-Ca NPs and Hc@CP-Ca NPs generated a rapid-onset and long-lasting hypoglycemic effect following gavage in type 1 diabetic mellitus (T1DM) rats. The pharmacological activity and the relative bioavailability were increased to 13.5% and 12.2%, respectively. Thus, these results indicated that CHP assembled NPs may provide a promising potential for oral insulin delivery by protection and absorption promotion.