Preparation and in vitro and in vivo characterization of cyclosporin A-loaded, PEGylated chitosan-modified, lipid-based nanoparticles

Ling Zhang,1,2,# Zhi-Liang Zhao,3,# Xiao-Hong Wei,1 Jin-Hua Liu21School of Medicine, 2College of Material, Chemistry and Chemical Engineering, Hangzhou Normal University, 3Tongde Hospital of Zhejiang Province, Hangzhou, People&rsquo;s Republic of China #These authors contributed equally to t...

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Autores principales:	Zhang L, Zhao Z-L, Wei X-H, Liu J-H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8e26d091b3f24bfb91fffdad2691b022
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spelling	oai:doaj.org-article:8e26d091b3f24bfb91fffdad2691b0222021-12-02T02:42:18ZPreparation and in vitro and in vivo characterization of cyclosporin A-loaded, PEGylated chitosan-modified, lipid-based nanoparticles1176-91141178-2013https://doaj.org/article/8e26d091b3f24bfb91fffdad2691b0222013-02-01T00:00:00Zhttp://www.dovepress.com/preparation-and-in-vitro-and-in-vivo-characterization-of-cyclosporin-a-a12136https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Ling Zhang,1,2,# Zhi-Liang Zhao,3,# Xiao-Hong Wei,1 Jin-Hua Liu21School of Medicine, 2College of Material, Chemistry and Chemical Engineering, Hangzhou Normal University, 3Tongde Hospital of Zhejiang Province, Hangzhou, People&rsquo;s Republic of China #These authors contributed equally to this paperBackground and methods: A new cyclosporin A-loaded, PEGylated chitosan-modified lipid-based nanoparticle was developed to improve upon the formulation of cyclosporin A. PEGylated chitosan, synthesized in three steps using mild reaction conditions, was used to modify the nanoparticles. Cyclosporin A-loaded, PEGylated chitosan-modified nanoparticles were prepared using an emulsification/solvent evaporation method. The drug content and encapsulation efficiency of the cyclosporin A-loaded, PEGylated chitosan-modified nanoparticles were measured by high-performance liquid chromatography. The average size of the nanoparticles was determined by transmission electron microscopy and dynamic light scattering. The pharmacokinetic behavior of the nanoparticles was investigated in rabbits after intravenous injection. Cyclosporin A concentrations in a whole blood sample were analyzed by high-performance liquid chromatography using tamoxifen as the internal standard. The pharmacokinetic parameters were calculated using the 3p87 software program.Results: Fourier transform infrared spectroscopy and nuclear magnetic resonance confirmed the structure of PEGylated chitosan. The drug content and encapsulation efficiency of the cyclosporin A-loaded, PEGylated chitosan-modified nanoparticles were 37.04% and 69.22%, respectively. The average size of the nanoparticles was 89.4 nm. The nanoparticles released 30% cyclosporin A-loaded in 48 hours in vitro, with no initial burst release. The mode of release in vitro was prone to bulk erosion. The in vivo results showed the biological half-life of the elimination phase (t1/2&beta;) of the nanoparticles was 21 times longer than that of the cyclosporin A solution, and the area under the curve for the nanoparticles was 25.8 times greater than that of the cyclosporin A solution.Conclusion: Modification of PEGylated chitosan prolonged the retention time of the nanoparticles in the circulatory system and improved the bioavailability of cyclosporin A.Keywords: nanoparticle, PEGylation, chitosan, pharmacokinetics, cyclosporin A, long circulation, bioavailabilityZhang LZhao Z-LWei X-HLiu J-HDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 601-610 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Zhang L Zhao Z-L Wei X-H Liu J-H Preparation and in vitro and in vivo characterization of cyclosporin A-loaded, PEGylated chitosan-modified, lipid-based nanoparticles
description	Ling Zhang,1,2,# Zhi-Liang Zhao,3,# Xiao-Hong Wei,1 Jin-Hua Liu21School of Medicine, 2College of Material, Chemistry and Chemical Engineering, Hangzhou Normal University, 3Tongde Hospital of Zhejiang Province, Hangzhou, People&rsquo;s Republic of China #These authors contributed equally to this paperBackground and methods: A new cyclosporin A-loaded, PEGylated chitosan-modified lipid-based nanoparticle was developed to improve upon the formulation of cyclosporin A. PEGylated chitosan, synthesized in three steps using mild reaction conditions, was used to modify the nanoparticles. Cyclosporin A-loaded, PEGylated chitosan-modified nanoparticles were prepared using an emulsification/solvent evaporation method. The drug content and encapsulation efficiency of the cyclosporin A-loaded, PEGylated chitosan-modified nanoparticles were measured by high-performance liquid chromatography. The average size of the nanoparticles was determined by transmission electron microscopy and dynamic light scattering. The pharmacokinetic behavior of the nanoparticles was investigated in rabbits after intravenous injection. Cyclosporin A concentrations in a whole blood sample were analyzed by high-performance liquid chromatography using tamoxifen as the internal standard. The pharmacokinetic parameters were calculated using the 3p87 software program.Results: Fourier transform infrared spectroscopy and nuclear magnetic resonance confirmed the structure of PEGylated chitosan. The drug content and encapsulation efficiency of the cyclosporin A-loaded, PEGylated chitosan-modified nanoparticles were 37.04% and 69.22%, respectively. The average size of the nanoparticles was 89.4 nm. The nanoparticles released 30% cyclosporin A-loaded in 48 hours in vitro, with no initial burst release. The mode of release in vitro was prone to bulk erosion. The in vivo results showed the biological half-life of the elimination phase (t1/2&beta;) of the nanoparticles was 21 times longer than that of the cyclosporin A solution, and the area under the curve for the nanoparticles was 25.8 times greater than that of the cyclosporin A solution.Conclusion: Modification of PEGylated chitosan prolonged the retention time of the nanoparticles in the circulatory system and improved the bioavailability of cyclosporin A.Keywords: nanoparticle, PEGylation, chitosan, pharmacokinetics, cyclosporin A, long circulation, bioavailability
format	article
author	Zhang L Zhao Z-L Wei X-H Liu J-H
author_facet	Zhang L Zhao Z-L Wei X-H Liu J-H
author_sort	Zhang L
title	Preparation and in vitro and in vivo characterization of cyclosporin A-loaded, PEGylated chitosan-modified, lipid-based nanoparticles
title_short	Preparation and in vitro and in vivo characterization of cyclosporin A-loaded, PEGylated chitosan-modified, lipid-based nanoparticles
title_full	Preparation and in vitro and in vivo characterization of cyclosporin A-loaded, PEGylated chitosan-modified, lipid-based nanoparticles
title_fullStr	Preparation and in vitro and in vivo characterization of cyclosporin A-loaded, PEGylated chitosan-modified, lipid-based nanoparticles
title_full_unstemmed	Preparation and in vitro and in vivo characterization of cyclosporin A-loaded, PEGylated chitosan-modified, lipid-based nanoparticles
title_sort	preparation and in vitro and in vivo characterization of cyclosporin a-loaded, pegylated chitosan-modified, lipid-based nanoparticles
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/8e26d091b3f24bfb91fffdad2691b022
work_keys_str_mv	AT zhangl preparationandinvitroandinvivocharacterizationofcyclosporinaloadedpegylatedchitosanmodifiedlipidbasednanoparticles AT zhaozl preparationandinvitroandinvivocharacterizationofcyclosporinaloadedpegylatedchitosanmodifiedlipidbasednanoparticles AT weixh preparationandinvitroandinvivocharacterizationofcyclosporinaloadedpegylatedchitosanmodifiedlipidbasednanoparticles AT liujh preparationandinvitroandinvivocharacterizationofcyclosporinaloadedpegylatedchitosanmodifiedlipidbasednanoparticles
_version_	1718402233450627072

Preparation and in vitro and in vivo characterization of cyclosporin A-loaded, PEGylated chitosan-modified, lipid-based nanoparticles

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