Chitosan modified cerasomes incorporating poly (vinyl pyrrolidone) for oral insulin delivery

摘要

The most significant finding of this study is that a hybrid liposomal cerasome with high stability and good biocompatibility was successfully developed for oral insulin delivery by incorporating poly (vinyl pyrrolidone) (PVP) into the cerasome followed by coating with chitosan (CS). These PVP and CS modified cerasomes (PCCs) were positively charged with an average size of about 247.8 +/- 3.3 nm. It was found that insulin-loaded PCCs could maintain their size and retain the encapsulated insulin over a period of 90 days, suitable for uptake within the gastrointestinal tract. PCCs had an encapsulation efficiency of 82.03 +/- 7.53% and drug loading content of 0.36 +/- 0.03 (g g(-1)), much higher than that of unmodified cerasomes (45.91 +/- 1.87% and 0.27 +/- 0.01 (g g(-1))). The in vitro experiments showed that less than 65% insulin was released from PCCs after 160 h under physiological conditions. The oral administration of insulin-loaded unmodified cerasomes resulted in almost no change in blood glucose levels in hyperglycemic rats. On the contrary, the insulin-loaded PCCs rapidly decreased the plasma glucose levels which reached their maximum around 2 h (17.15% from the initial value) after oral administration. Especially, the insulin-loaded PCCs displayed a prolonged and stable glucose-lowering profile over a period of over 10 h. Both the PVP and the CS can increase the half life of the cerasomes in vivo. In addition, CS as a mucoadhesive polymer can open tight junctions of intestinal epithelial layers, resulting in high oral bioavailability. In other words, the PCCs have great potential as oral formulations for delivering therapeutic protein or peptide drugs.