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  • N-octyl-N-Arginine chitosan micelles as an oral delivery system of insulin.

N-octyl-N-Arginine chitosan micelles as an oral delivery system of insulin.

Journal of biomedical nanotechnology (2013-04-30)
Zhen-Hai Zhang, Sarra Abbad, Rui-Rui Pan, Ayman Y Waddad, Lu-Lu Hou, Hui-Xia Lv, Jian-Ping Zhou
ABSTRACT

N-octyl-N-Arginine chitosan (OACS) was synthesized in an attempt to combine the permeation enhancing effects of arginine-rich peptides and the drug loading capacity of the amphipathic polymers for insulin oral delivery. OACS self-assembled micelles of insulin were prepared by the conventional stirring technique, which were characterized by Dynamic light scattering, transmission electron microscopy and differential scanning calorimetry. Molecular docking by Discovery studio software confirmed that the interactions between OACS and insulin were mostly electrostatic in nature. In vitro, the result of the degradation experiment by enzyme showed that the OACS has a relative protective effect for insulin from proteolyses. Compared to the insulin solution, OACS micelles increased the Caco-2 cell's internalization by up to 22.3 folds. In vivo, the pharmacological activity PA% of series OACS-insulin micelles ranged from 7.7%-16.8%. Meanwhile by increasing arginine degree of the substitution both the uptake in Caco-2 cells and the hypoglycemic effect in diabetic rats were enhanced. Therefore, it is concluded that using arginine polymeric micelles for the enhancement of oral insulin delivery is a promising approach for the oral peptide delivery.

MATERIALS
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