title: The glucose-lowering potential of exenatide delivered orally via goblet cell-targeting nanoparticles.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  CSK peptide-modified chitosan nanoparticles could be a potential therapeutics for Type II diabetes patients.
authors.affiliation: School of Life Sciences, Jilin University, Changchun, 130012, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Chenhui
authors.initials: C
authors.lastname: Wang
authors.forename: Rongcai
authors.initials: R
authors.lastname: Liang
authors.forename: Fengying
authors.initials: F
authors.lastname: Sun
authors.forename: Yanan
authors.initials: Y
authors.lastname: Shi
authors.forename: Aiping
authors.initials: A
authors.lastname: Wang
authors.forename: Wanhui
authors.initials: W
authors.lastname: Liu
authors.forename: Kaoxiang
authors.initials: K
authors.lastname: Sun
authors.forename: Youxin
authors.initials: Y
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers; D000077270:Exenatide; D020397:Goblet Cells / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D008297:Male; D050997:Nanomedicine; D053758:Nanoparticles; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D010539:Permeability; D017207:Rats, Sprague-Dawley; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution; D014688:Venoms / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D001786:Blood Glucose; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D009842:Oligopeptides; D010455:Peptides; D014688:Venoms; D048271:Chitosan; D000077270:Exenatide