A cell-penetrating peptide mediated chitosan nanocarriers for improving intestinal insulin delivery

Carbohydr Polym. 2017 Oct 15:174:182-189. doi: 10.1016/j.carbpol.2017.06.061. Epub 2017 Jun 17.

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.

Keywords: Absorption efficiency; Cell-penetrating peptide; Chitosan; Insulin; Nanoparticle.

MeSH terms

  • Administration, Oral
  • Animals
  • Cell-Penetrating Peptides / chemistry*
  • Chitosan / chemistry*
  • Diabetes Mellitus, Experimental / drug therapy*
  • Drug Carriers / chemistry*
  • Insulin / administration & dosage*
  • Nanoparticles
  • Rats

Substances

  • Cell-Penetrating Peptides
  • Drug Carriers
  • Insulin
  • Chitosan