Glucose- and temperature-sensitive nanoparticles for insulin delivery

Jun-Zi Wu,1 Gareth R Williams,2 He-Yu Li,1 Dongxiu Wang,3 Huanling Wu,1 Shu-De Li,4 Li-Min Zhu1 1College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China; 2UCL School of Pharmacy, University College London, London, UK; 3Central...

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Autores principales:	Wu JZ, Williams GR, Li HY, Wang D, Wu H, Li SD, Zhu LM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Diethylene glycol dimethacrylate 3-acrylamidophenyl boronic acid nanoparticle thermosensitive glucose-sensitive insulin delivery. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/56043d95602e407993bc8ff47387ac53
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spelling	oai:doaj.org-article:56043d95602e407993bc8ff47387ac532021-12-02T05:39:10ZGlucose- and temperature-sensitive nanoparticles for insulin delivery1178-2013https://doaj.org/article/56043d95602e407993bc8ff47387ac532017-05-01T00:00:00Zhttps://www.dovepress.com/glucose--and-temperature-sensitive-nanoparticles-for-insulin-delivery-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jun-Zi Wu,1 Gareth R Williams,2 He-Yu Li,1 Dongxiu Wang,3 Huanling Wu,1 Shu-De Li,4 Li-Min Zhu1 1College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China; 2UCL School of Pharmacy, University College London, London, UK; 3Central Laboratory, Environmental Monitoring Center of Kunming, 4School of Basic Medical Sciences, Kunming Medical University, Kunming, People’s Republic of China Abstract: Glucose- and temperature-sensitive polymers of a phenylboronic acid derivative and diethylene glycol dimethacrylate (poly(3-acrylamidophenyl boronic acid-b-diethylene glycol methyl ether methacrylate); p(AAPBA-b-DEGMA)) were prepared by reversible addition–fragmentation chain transfer polymerization. Successful polymerization was evidenced by 1H nuclear magnetic resonance and infrared spectroscopy, and the polymers were further explored in terms of their glass transition temperatures and by gel permeation chromatography (GPC). The materials were found to be temperature sensitive, with lower critical solution temperatures in the region of 12°C–47°C depending on the monomer ratio used for reaction. The polymers could be self-assembled into nanoparticles (NPs), and the zeta potential and size of these particles were determined as a function of temperature and glucose concentration. Subsequently, the optimum NP formulation was loaded with insulin, and the drug release was studied. We found that insulin was easily encapsulated into the p(AAPBA-b-DEGMA) NPs, with a loading capacity of ~15% and encapsulation efficiency of ~70%. Insulin release could be regulated by changes in temperature and glucose concentration. Furthermore, the NPs were non-toxic both in vitro and in vivo. Finally, the efficacy of the formulations at managing blood glucose levels in a murine hyperglycemic diabetes model was studied. The insulin-loaded NPs could reduce blood glucose levels over an extended period of 48 h. Since they are both temperature and glucose sensitive and offer a sustained-release profile, these systems may comprise potent new formulations for insulin delivery. Keywords: diethylene glycol methyl ether methacrylate, 3-acrylamidophenylboronic acid, nanoparticle, thermosensitive, glucose sensitive, insulin deliveryWu JZWilliams GRLi HYWang DWu HLi SDZhu LMDove Medical PressarticleDiethylene glycol dimethacrylate3-acrylamidophenyl boronic acidnanoparticlethermosensitiveglucose-sensitiveinsulin delivery.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 4037-4057 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diethylene glycol dimethacrylate 3-acrylamidophenyl boronic acid nanoparticle thermosensitive glucose-sensitive insulin delivery. Medicine (General) R5-920
spellingShingle	Diethylene glycol dimethacrylate 3-acrylamidophenyl boronic acid nanoparticle thermosensitive glucose-sensitive insulin delivery. Medicine (General) R5-920 Wu JZ Williams GR Li HY Wang D Wu H Li SD Zhu LM Glucose- and temperature-sensitive nanoparticles for insulin delivery
description	Jun-Zi Wu,1 Gareth R Williams,2 He-Yu Li,1 Dongxiu Wang,3 Huanling Wu,1 Shu-De Li,4 Li-Min Zhu1 1College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China; 2UCL School of Pharmacy, University College London, London, UK; 3Central Laboratory, Environmental Monitoring Center of Kunming, 4School of Basic Medical Sciences, Kunming Medical University, Kunming, People’s Republic of China Abstract: Glucose- and temperature-sensitive polymers of a phenylboronic acid derivative and diethylene glycol dimethacrylate (poly(3-acrylamidophenyl boronic acid-b-diethylene glycol methyl ether methacrylate); p(AAPBA-b-DEGMA)) were prepared by reversible addition–fragmentation chain transfer polymerization. Successful polymerization was evidenced by 1H nuclear magnetic resonance and infrared spectroscopy, and the polymers were further explored in terms of their glass transition temperatures and by gel permeation chromatography (GPC). The materials were found to be temperature sensitive, with lower critical solution temperatures in the region of 12°C–47°C depending on the monomer ratio used for reaction. The polymers could be self-assembled into nanoparticles (NPs), and the zeta potential and size of these particles were determined as a function of temperature and glucose concentration. Subsequently, the optimum NP formulation was loaded with insulin, and the drug release was studied. We found that insulin was easily encapsulated into the p(AAPBA-b-DEGMA) NPs, with a loading capacity of ~15% and encapsulation efficiency of ~70%. Insulin release could be regulated by changes in temperature and glucose concentration. Furthermore, the NPs were non-toxic both in vitro and in vivo. Finally, the efficacy of the formulations at managing blood glucose levels in a murine hyperglycemic diabetes model was studied. The insulin-loaded NPs could reduce blood glucose levels over an extended period of 48 h. Since they are both temperature and glucose sensitive and offer a sustained-release profile, these systems may comprise potent new formulations for insulin delivery. Keywords: diethylene glycol methyl ether methacrylate, 3-acrylamidophenylboronic acid, nanoparticle, thermosensitive, glucose sensitive, insulin delivery
format	article
author	Wu JZ Williams GR Li HY Wang D Wu H Li SD Zhu LM
author_facet	Wu JZ Williams GR Li HY Wang D Wu H Li SD Zhu LM
author_sort	Wu JZ
title	Glucose- and temperature-sensitive nanoparticles for insulin delivery
title_short	Glucose- and temperature-sensitive nanoparticles for insulin delivery
title_full	Glucose- and temperature-sensitive nanoparticles for insulin delivery
title_fullStr	Glucose- and temperature-sensitive nanoparticles for insulin delivery
title_full_unstemmed	Glucose- and temperature-sensitive nanoparticles for insulin delivery
title_sort	glucose- and temperature-sensitive nanoparticles for insulin delivery
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/56043d95602e407993bc8ff47387ac53
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Glucose- and temperature-sensitive nanoparticles for insulin delivery

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