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  • Title: The glucose-lowering potential of exenatide delivered orally via goblet cell-targeting nanoparticles.
    Author: Li X, Wang C, Liang R, Sun F, Shi Y, Wang A, Liu W, Sun K, Li Y.
    Journal: Pharm Res; 2015 Mar; 32(3):1017-27. PubMed ID: 25270570.
    Abstract:
    PURPOSE: Exenatide, a potent insulinotropic agent, can be used for the treatment of non-insulin-dependent diabetes mellitus. However, the need for frequent injections seriously limits its therapeutic utility. The aim of present report was to develop an orally available exenatide formulation using goblet cell-targeting nanoparticles (NPs). METHOD: The exenatide-loaded nanoparticles were prepared with modified chitosan which was conjugated with a goblet cell-target peptide, CSKSSDYQC (CSK) peptide. RESULTS: The CSK-chitosan nanoparticles shown reduced chitosan toxicity and enhanced the permeation of drugs across the Caco-2/HT-29 co-cultured cell monolayer, which simulated the intestinal epithelium. Following the oral administration of near-infrared fluorescent probe Cy-7-loaded NPs to mice, the distribution of the drugs was investigated with a near-infrared in vivo image system (FX Pro, Bruker, USA). The results showed that Cy-7 fluorescence disseminated from the oesophagus, then to stomach and small intestine and then was absorbed into hepatic, finally into the bladder; over time, Cy-7 was metabolized and excreted. The bioavailability of the modified nanoparticles was found to be 1.7-fold higher compared with the unmodified ones, and the hypoglycemic effect was also better. CONCLUSION: CSK peptide-modified chitosan nanoparticles could be a potential therapeutics for Type II diabetes patients.
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