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

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 an...

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Autor principal:	Tong F
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Block copolymer PELG50-g-PLL3 exenatide hypoglycemic action diabetic nephropathy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/06dc927877e14725af143f34bd1b4e5e
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spelling	oai:doaj.org-article:06dc927877e14725af143f34bd1b4e5e2021-12-02T02:31:35ZPreparation of exenatide-loaded linear poly(ethylene glycol)-brush poly(L-lysine) block copolymer: potential implications on diabetic nephropathy1178-2013https://doaj.org/article/06dc927877e14725af143f34bd1b4e5e2017-06-01T00:00:00Zhttps://www.dovepress.com/preparation-of-exenatide-loaded-linear-polyethylene-glycol-brush-polyl-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Fei 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 nephropathyTong FDove Medical PressarticleBlock copolymerPELG50-g-PLL3exenatidehypoglycemic actiondiabetic nephropathyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 4663-4678 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Block copolymer PELG50-g-PLL3 exenatide hypoglycemic action diabetic nephropathy Medicine (General) R5-920
spellingShingle	Block copolymer PELG50-g-PLL3 exenatide hypoglycemic action diabetic nephropathy Medicine (General) R5-920 Tong F Preparation of exenatide-loaded linear poly(ethylene glycol)-brush poly(L-lysine) block copolymer: potential implications on diabetic nephropathy
description	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
format	article
author	Tong F
author_facet	Tong F
author_sort	Tong F
title	Preparation of exenatide-loaded linear poly(ethylene glycol)-brush poly(L-lysine) block copolymer: potential implications on diabetic nephropathy
title_short	Preparation of exenatide-loaded linear poly(ethylene glycol)-brush poly(L-lysine) block copolymer: potential implications on diabetic nephropathy
title_full	Preparation of exenatide-loaded linear poly(ethylene glycol)-brush poly(L-lysine) block copolymer: potential implications on diabetic nephropathy
title_fullStr	Preparation of exenatide-loaded linear poly(ethylene glycol)-brush poly(L-lysine) block copolymer: potential implications on diabetic nephropathy
title_full_unstemmed	Preparation of exenatide-loaded linear poly(ethylene glycol)-brush poly(L-lysine) block copolymer: potential implications on diabetic nephropathy
title_sort	preparation of exenatide-loaded linear poly(ethylene glycol)-brush poly(l-lysine) block copolymer: potential implications on diabetic nephropathy
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/06dc927877e14725af143f34bd1b4e5e
work_keys_str_mv	AT tongf preparationofexenatideloadedlinearpolyethyleneglycolbrushpolyllysineblockcopolymerpotentialimplicationsondiabeticnephropathy
_version_	1718402387272531968

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

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