Abstract
To overcome barriers for oral delivery of insulin, the chitosan(CS)-based nanocarriers with a novel cell penetrating peptide (SAR6EW) have been prepared and evaluated in this study. Characterization measurements showed that SAR6EW/CS/insulin-NPs displayed global particles with smooth surfaces and an average diameter about 150nm. The entrapment efficiency and loading rates of insulin were 75.36% and 7.58%, respectively. Insulin could be released constantly from SAR6EW/CS/insulin-NPs in vitro. Furthermore, SAR6EW/CS/insulin-NPs could facilitate the uptake of insulin and induce a significantly higher internalization of insulin via adding clathrin and caveolae mediated endocytosis. In addition, in vivo hypoglycemic studies showed that orally administrated SAR6EW/CS/insulin-NPs produced a better hypoglycemic effect as compared with CS/insulin-NPs in diabetic rats. Meanwhile, no significant cytotoxicity of the nanoparticles was observed. In conclusion, SAR6EW-mediated chitosan nanocarriers showed sufficient effectiveness for oral delivery of insulin. This delivery system is also promising for the delivery of other protein drugs by oral administration.
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