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Preparation of exenatide-loaded linear poly(ethylene glycol)-brush poly(L-lysine) block copolymer: potential implications on diabetic nephropathy

Authors Tong F

Received 10 March 2017

Accepted for publication 23 May 2017

Published 29 June 2017 Volume 2017:12 Pages 4663—4678

DOI https://doi.org/10.2147/IJN.S136646

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Alexander Kharlamov

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun


Fei Tong

Department of Pathology and Pathophysiology, Provincial Key Discipline of Pharmacology, Jiaxing University Medical College, Jiaxing, Zhejiang, People’s Republic of China

Abstract: The poly(ethylene glycol)-b-brush poly(l-lysine) polymer (PEG-b-(PELG50-g-PLL3)) was synthesized and evaluated as a nanocarrier for prolonging delivery of exenatide through the abdominal subcutaneous injection route. The isoelectric point of exenatide was 4.86, and exenatide could combine with PEG-b-(PELG50-g-PLL3) polymers via electrostatic interactions at pH 7.4. This polymer was a good candidate for achieving prolonged drug delivery for exenatide, considering its high molecular weight. Besides the physicochemical characterization of the polymer, in vitro and in vivo applications were researched as a sustained exenatide delivery system. In the in vitro release research, 20.16%–76.88% of total exenatide was released from the PEG-b-(PELG50-g-PLL3) polymer within 7 days. The synthesized block-brush polymers and exenatide–block-brush polymers were analyzed by nuclear magnetic resonance spectroscopy, gel permeation chromatography, transmission electron microscopy, nanoparticle size instrument, and scanning electron microscopy. The best formulation was selected for in vivo experimentation to achieve blood glucose control in diabetic rat models using free exenatide as the control. The hypoglycemic action of the formulation following subcutaneous injection in diabetic rats lasted 7 days, and the results indicated that exenatide–block-brush polymers demonstrate enhanced long-acting hypoglycemic action. Besides the hypoglycemic action, exenatide–block-brush polymers significantly alleviated diabetic nephropathy via improving renal function, decreasing oxidative stress injury, decreasing urinary albumin excretion rate, mitigating albumin/creatinine ratio, reducing blood lipids, abating kidney index, weakening apoptosis, and downregulating expression of connective tissue growth factor. All of the results suggested that PEG-b-(PELG50-g-PLL3) polymers could be used as potential exenatide nanocarriers, with efficient encapsulation and sustained release.

Keywords: block copolymer, PELG50-g-PLL3, exenatide, hypoglycemic action, diabetic nephropathy

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