Long-acting inhalable chitosan-coated poly(lactic-co-glycolic acid) nanoparticles containing hydrophobically modified exendin-4 for treating type 2 diabetes

Changkyu Lee,1 Ji Su Choi,1 Insoo Kim,1 Kyung Taek Oh,2 Eun Seong Lee,3 Eun-Seok Park,1 Kang Choon Lee,1 Yu Seok Youn11School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; 2College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 3Division of Biotechnology, The Catholic...

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Autores principales:	Lee C, Choi JS, Kim I, Oh KT, Lee ES, Park ES, Lee KC, Youn YS
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/72454162d43f416b93ccbd3efb5e85ee
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spelling	oai:doaj.org-article:72454162d43f416b93ccbd3efb5e85ee2021-12-02T02:16:50ZLong-acting inhalable chitosan-coated poly(lactic-co-glycolic acid) nanoparticles containing hydrophobically modified exendin-4 for treating type 2 diabetes1176-91141178-2013https://doaj.org/article/72454162d43f416b93ccbd3efb5e85ee2013-08-01T00:00:00Zhttp://www.dovepress.com/long-acting-inhalable-chitosan-coated-polylactic-co-glycolic-acid-nano-a13978https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Changkyu Lee,1 Ji Su Choi,1 Insoo Kim,1 Kyung Taek Oh,2 Eun Seong Lee,3 Eun-Seok Park,1 Kang Choon Lee,1 Yu Seok Youn11School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; 2College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 3Division of Biotechnology, The Catholic University of Korea, Bucheon-si, Republic of KoreaAbstract: Inhalable glycol chitosan-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing palmitic acid-modified exendin-4 (Pal-Ex4) (chitosan Pal-Ex4 PLGA NPs) were prepared and characterized. The surface morphology, particle size, and zeta potential of chitosan Pal-Ex4 PLGA NPs were investigated, and the adsorption and cytotoxicity of chitosan Pal-Ex4 PLGA NPs were evaluated in human lung epithelial cells (A549). Finally, the lung deposition characteristics and hypoglycemia caused by chitosan Pal-Ex4 PLGA NPs were evaluated after pulmonary administration in imprinting control region (ICR) and type 2 diabetic db/db mice. Results showed that chitosan Pal-Ex4 PLGA NPs were spherical, compact and had a diameter of ~700 nm and a positive surface charge of +28.5 mV. Chitosan-coated PLGA NPs were adsorbed onto A549 cells much more so than non-coated PLGA NPs. Pal-Ex4 release from chitosan-coated PLGA NPs was delayed by as much as 1.5 days as compared with chitosan-coated Ex4 PLGA NPs. In addition, chitosan-coated PLGA NPs remained in the lungs for ~72 hours after pulmonary administration, whereas most non-coated PLGA NPs were lost at 8 hours after administration. Furthermore, the hypoglycemic efficacy of inhaled chitosan Pal-Ex4 PLGA NPs was 3.1-fold greater than that of chitosan Ex4 PLGA NPs in db/db mice. The authors believe chitosan Pal-Ex4 PLGA NPs have considerable potential as a long-acting inhalation delivery system for the treatment of type 2 diabetes.Keywords: chitosan-coating, PLGA nanoparticles, inhalation, exendin-4, type 2 diabetesLee CChoi JSKim IOh KTLee ESPark ESLee KCYoun YSDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 2975-2983 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Lee C Choi JS Kim I Oh KT Lee ES Park ES Lee KC Youn YS Long-acting inhalable chitosan-coated poly(lactic-co-glycolic acid) nanoparticles containing hydrophobically modified exendin-4 for treating type 2 diabetes
description	Changkyu Lee,1 Ji Su Choi,1 Insoo Kim,1 Kyung Taek Oh,2 Eun Seong Lee,3 Eun-Seok Park,1 Kang Choon Lee,1 Yu Seok Youn11School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; 2College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 3Division of Biotechnology, The Catholic University of Korea, Bucheon-si, Republic of KoreaAbstract: Inhalable glycol chitosan-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing palmitic acid-modified exendin-4 (Pal-Ex4) (chitosan Pal-Ex4 PLGA NPs) were prepared and characterized. The surface morphology, particle size, and zeta potential of chitosan Pal-Ex4 PLGA NPs were investigated, and the adsorption and cytotoxicity of chitosan Pal-Ex4 PLGA NPs were evaluated in human lung epithelial cells (A549). Finally, the lung deposition characteristics and hypoglycemia caused by chitosan Pal-Ex4 PLGA NPs were evaluated after pulmonary administration in imprinting control region (ICR) and type 2 diabetic db/db mice. Results showed that chitosan Pal-Ex4 PLGA NPs were spherical, compact and had a diameter of ~700 nm and a positive surface charge of +28.5 mV. Chitosan-coated PLGA NPs were adsorbed onto A549 cells much more so than non-coated PLGA NPs. Pal-Ex4 release from chitosan-coated PLGA NPs was delayed by as much as 1.5 days as compared with chitosan-coated Ex4 PLGA NPs. In addition, chitosan-coated PLGA NPs remained in the lungs for ~72 hours after pulmonary administration, whereas most non-coated PLGA NPs were lost at 8 hours after administration. Furthermore, the hypoglycemic efficacy of inhaled chitosan Pal-Ex4 PLGA NPs was 3.1-fold greater than that of chitosan Ex4 PLGA NPs in db/db mice. The authors believe chitosan Pal-Ex4 PLGA NPs have considerable potential as a long-acting inhalation delivery system for the treatment of type 2 diabetes.Keywords: chitosan-coating, PLGA nanoparticles, inhalation, exendin-4, type 2 diabetes
format	article
author	Lee C Choi JS Kim I Oh KT Lee ES Park ES Lee KC Youn YS
author_facet	Lee C Choi JS Kim I Oh KT Lee ES Park ES Lee KC Youn YS
author_sort	Lee C
title	Long-acting inhalable chitosan-coated poly(lactic-co-glycolic acid) nanoparticles containing hydrophobically modified exendin-4 for treating type 2 diabetes
title_short	Long-acting inhalable chitosan-coated poly(lactic-co-glycolic acid) nanoparticles containing hydrophobically modified exendin-4 for treating type 2 diabetes
title_full	Long-acting inhalable chitosan-coated poly(lactic-co-glycolic acid) nanoparticles containing hydrophobically modified exendin-4 for treating type 2 diabetes
title_fullStr	Long-acting inhalable chitosan-coated poly(lactic-co-glycolic acid) nanoparticles containing hydrophobically modified exendin-4 for treating type 2 diabetes
title_full_unstemmed	Long-acting inhalable chitosan-coated poly(lactic-co-glycolic acid) nanoparticles containing hydrophobically modified exendin-4 for treating type 2 diabetes
title_sort	long-acting inhalable chitosan-coated poly(lactic-co-glycolic acid) nanoparticles containing hydrophobically modified exendin-4 for treating type 2 diabetes
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/72454162d43f416b93ccbd3efb5e85ee
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Long-acting inhalable chitosan-coated poly(lactic-co-glycolic acid) nanoparticles containing hydrophobically modified exendin-4 for treating type 2 diabetes

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