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

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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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Authors and Affiliations

  1. School of Life Sciences, Jilin University, Changchun, 130012, China

    Xiang Li, Chenhui Wang, Rongcai Liang, Fengying Sun, Yanan Shi & Youxin Li

  2. State Key Laboratory of Long-acting & Targeting Drug Delivery System, No. 9 Baoyuan Road, 264003, Yantai, Shandong Province, China

    Xiang Li, Rongcai Liang, Yanan Shi, Aiping Wang, Wanhui Liu, Kaoxiang Sun & Youxin Li

  3. School of Pharmacy, Yantai University, No. 30 Qingquan Road, Yantai, China

    Rongcai Liang, Aiping Wang, Wanhui Liu, Kaoxiang Sun & Youxin Li

Authors
  1. Xiang Li
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  2. Chenhui Wang
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  3. Rongcai Liang
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  4. Fengying Sun
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  5. Yanan Shi
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  6. Aiping Wang
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  7. Wanhui Liu
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  8. Kaoxiang Sun
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  9. Youxin Li
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Correspondence to Youxin Li.

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Li, X., Wang, C., Liang, R. et al. The Glucose-Lowering Potential of Exenatide Delivered Orally via Goblet Cell- Targeting Nanoparticles. Pharm Res 32, 1017–1027 (2015). https://doi.org/10.1007/s11095-014-1513-1

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  • DOI: https://doi.org/10.1007/s11095-014-1513-1

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