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Long-Acting Phospholipid Gel of Exenatide for Long-Term Therapy of Type II Diabetes

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Abstract

Purpose

This study aimed to develop a sustained-release formulation of exenatide (EXT) for the long-term therapeutic efficacy in the treatment of type II diabetes.

Methods

In this study, we present an injectable phospholipid gel by mixing biocompatible phospholipid S100, medium chain triglyceride (MCT) with 85% (w/w) ethanol. A systemic pre-formulation study has been carried out to improve the stability of EXT during formulation fabrication. With the optimized formulation, the pharmacokinetic profiles in rats were studied and two diabetic animal models were employed to evaluate the therapeutic effect of EXT phospholipid gel via a single subcutaneous injection versus repeated injections of normal saline and EXT solution.

Results

With optimized formulation, sustained release of exenatide in vivo for over three consecutive weeks was observed after one single subcutaneous injection. Moreover, the pharmacodynamic study in two diabetic models justified that the gel formulation displayed a comparable hypoglycemic effect and controlled blood glucose level compared with exenatide solution treated group.

Conclusions

EXT-loaded phospholipid gel represents a promising controlled release system for long-term therapy of type II diabetes.

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Abbreviations

DDP-IV:

Dipeptidyl peptidase IV

EMA:

European medicines agency

EXT:

Exenatide

FDA:

Food and drug administration

FITC:

Fluoresceinisothiocyanate

GLP-1:

Glucagon-like peptide-1

HP-β-CD:

Hydroxypropyl-β-cyclodextrin

MCT:

Medium chain triglyceride

PPSG:

Phospholipid-based phase separation gel

STZ:

Streptozocin

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors are grateful for the financial support from the National S&T Major Project of China (2014ZX09507001) and Sichuan University Startup Foundation for Talents (2082204174131). The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University, No. 17, Section 3, Southern Renmin Road, Chengdu, 610041, China

    Mei Hu, Yu Zhang, Nanxi Xiang, Ying Zhong, Tao Gong, Zhi-Rong Zhang & Yao Fu

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  1. Mei Hu
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  2. Yu Zhang
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  3. Nanxi Xiang
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  4. Ying Zhong
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Correspondence to Yao Fu.

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Hu, M., Zhang, Y., Xiang, N. et al. Long-Acting Phospholipid Gel of Exenatide for Long-Term Therapy of Type II Diabetes. Pharm Res 33, 1318–1326 (2016). https://doi.org/10.1007/s11095-016-1873-9

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  • DOI: https://doi.org/10.1007/s11095-016-1873-9

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