The Glucose-Lowering Potential of Exenatide Delivered Orally via Goblet Cell- Targeting Nanoparticles

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• 作者：Xiang Li (1) (2)
  Chenhui Wang (1)
  Rongcai Liang (1) (2) (3)
  Fengying Sun (1)
  Yanan Shi (1) (2)
  Aiping Wang (2) (3)
  Wanhui Liu (2) (3)
  Kaoxiang Sun (2) (3)
  Youxin Li (1) (2) (3)
  
  1. School of Life Sciences ; Jilin University ; Changchun ; 130012 ; China
  2. State Key Laboratory of Long-acting & Targeting Drug Delivery System ; No. 9 Baoyuan Road ; 264003 ; Yantai ; Shandong Province ; China
  3. School of Pharmacy ; Yantai University ; No. 30 Qingquan Road ; Yantai ; China
  
• 关键词：CSK peptide ; modified chitosan ; exenatide ; goblet cell ; targeting nanoparticles ; in vivo image system ; oral delivery system
• 刊名：Pharmaceutical Research
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：32
• 期：3
• 页码：1017-1027
• 全文大小：2,271 KB
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  3. Goke R, Fehmann HC, Linn T, Schmidt H, Krause M, Eng J, / et al. Exendin-4 is a high potency agonist and truncated exendin-(9鈥?9)-amide an antagonist at the glucagon-like peptide 1-(7鈥?6)-amide receptor of insulin-secreting beta-cells. J Biol Chem. 1993;268:19650鈥?.
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• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Pharmacology and Toxicology
  Pharmacy
  Biochemistry
  Medical Law
  Biomedical Engineering
  
• 出版者：Springer Netherlands
• ISSN：1573-904X

文摘

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.