Polymeric nanoparticles conjugate a novel heptapeptide as an epidermal growth factor receptor-active targeting ligand for doxorubicin

Chia Wen Liu,1,2 Wen Jen Lin11Graduate Institute of Pharmaceutical Sciences, College of Medicine, National Taiwan University, Taipei; 2Drug Delivery Department, Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu, TaiwanBackground: This study was performed...

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Autores principales:	Liu CW, Lin WJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/14e1f955835a4a8c9d24cce75b5b1f73
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spelling	oai:doaj.org-article:14e1f955835a4a8c9d24cce75b5b1f732021-12-02T01:42:05ZPolymeric nanoparticles conjugate a novel heptapeptide as an epidermal growth factor receptor-active targeting ligand for doxorubicin1176-91141178-2013https://doaj.org/article/14e1f955835a4a8c9d24cce75b5b1f732012-08-01T00:00:00Zhttp://www.dovepress.com/polymeric-nanoparticles-conjugate-a-novel-heptapeptide-as-an-epidermal-a10859https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Chia Wen Liu,1,2 Wen Jen Lin11Graduate Institute of Pharmaceutical Sciences, College of Medicine, National Taiwan University, Taipei; 2Drug Delivery Department, Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu, TaiwanBackground: This study was performed to develop a functional poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG)-bearing amino-active end group for peptide conjugation.Methods and results: PLGA was preactivated following by copolymerization with PEG diamine. The resulting amphiphilic PLGA-PEG copolymer bearing 97.0% of amino end groups had a critical micelle concentration of 3.0 &times; 10-8 mol/L, and the half-effective inhibition concentration (IC50) of the prepared PLGA-PEG nanoparticles was &gt;100 mg/mL, which was much higher than that of PLGA nanoparticles (1.02 &plusmn; 0.37 mg/mL). The amphiphilic properties of PLGA-PEG spontaneously formed a core-shell conformation in the aqueous environment, and this special feature provided the amino group on the PEG chain scattered on the surface of PLGA-PEG nanoparticles for efficient peptide conjugation. The peptide-conjugated PLGA-PEG nanoparticles showed three-fold higher uptake than peptide-free PLGA-PEG nanoparticles in a SKOV3 cell line with high expression of epidermal growth factor receptor. Both peptide-conjugated and peptide-free PLGA-PEG nanoparticles were used as nanocarriers for delivery of doxorubicin. Although the rate of release of doxorubicin from both nanoparticles was similar, drug release at pH 4.0 (500 U lipase) was faster than at pH 7.4. The IC50 of doxorubicin-loaded peptide-conjugated PLGA-PEG nanoparticles in SKOV3 cells (0.05 &plusmn; 0.03 &micro;g/mL) was much lower (by 62.4-fold) than that of peptide-free PLGA-PEG nanoparticles (3.12 &plusmn; 1.44 &micro;g/mL).Conclusion: This in vivo biodistribution study in SKOV3 tumor-bearing mice was further promising in that accumulation of doxorubicin in tumor tissue was in the order of peptide-conjugated PLGA-PEG nanoparticles &gt; peptide-free PLGA-PEG nanoparticles &gt; doxorubicin solution.Keywords: amphiphilic copolymer, peptide, nanoparticles, SKOV3 cell, doxorubicinLiu CWLin WJDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 4749-4767 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Liu CW Lin WJ Polymeric nanoparticles conjugate a novel heptapeptide as an epidermal growth factor receptor-active targeting ligand for doxorubicin
description	Chia Wen Liu,1,2 Wen Jen Lin11Graduate Institute of Pharmaceutical Sciences, College of Medicine, National Taiwan University, Taipei; 2Drug Delivery Department, Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu, TaiwanBackground: This study was performed to develop a functional poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG)-bearing amino-active end group for peptide conjugation.Methods and results: PLGA was preactivated following by copolymerization with PEG diamine. The resulting amphiphilic PLGA-PEG copolymer bearing 97.0% of amino end groups had a critical micelle concentration of 3.0 &times; 10-8 mol/L, and the half-effective inhibition concentration (IC50) of the prepared PLGA-PEG nanoparticles was &gt;100 mg/mL, which was much higher than that of PLGA nanoparticles (1.02 &plusmn; 0.37 mg/mL). The amphiphilic properties of PLGA-PEG spontaneously formed a core-shell conformation in the aqueous environment, and this special feature provided the amino group on the PEG chain scattered on the surface of PLGA-PEG nanoparticles for efficient peptide conjugation. The peptide-conjugated PLGA-PEG nanoparticles showed three-fold higher uptake than peptide-free PLGA-PEG nanoparticles in a SKOV3 cell line with high expression of epidermal growth factor receptor. Both peptide-conjugated and peptide-free PLGA-PEG nanoparticles were used as nanocarriers for delivery of doxorubicin. Although the rate of release of doxorubicin from both nanoparticles was similar, drug release at pH 4.0 (500 U lipase) was faster than at pH 7.4. The IC50 of doxorubicin-loaded peptide-conjugated PLGA-PEG nanoparticles in SKOV3 cells (0.05 &plusmn; 0.03 &micro;g/mL) was much lower (by 62.4-fold) than that of peptide-free PLGA-PEG nanoparticles (3.12 &plusmn; 1.44 &micro;g/mL).Conclusion: This in vivo biodistribution study in SKOV3 tumor-bearing mice was further promising in that accumulation of doxorubicin in tumor tissue was in the order of peptide-conjugated PLGA-PEG nanoparticles &gt; peptide-free PLGA-PEG nanoparticles &gt; doxorubicin solution.Keywords: amphiphilic copolymer, peptide, nanoparticles, SKOV3 cell, doxorubicin
format	article
author	Liu CW Lin WJ
author_facet	Liu CW Lin WJ
author_sort	Liu CW
title	Polymeric nanoparticles conjugate a novel heptapeptide as an epidermal growth factor receptor-active targeting ligand for doxorubicin
title_short	Polymeric nanoparticles conjugate a novel heptapeptide as an epidermal growth factor receptor-active targeting ligand for doxorubicin
title_full	Polymeric nanoparticles conjugate a novel heptapeptide as an epidermal growth factor receptor-active targeting ligand for doxorubicin
title_fullStr	Polymeric nanoparticles conjugate a novel heptapeptide as an epidermal growth factor receptor-active targeting ligand for doxorubicin
title_full_unstemmed	Polymeric nanoparticles conjugate a novel heptapeptide as an epidermal growth factor receptor-active targeting ligand for doxorubicin
title_sort	polymeric nanoparticles conjugate a novel heptapeptide as an epidermal growth factor receptor-active targeting ligand for doxorubicin
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/14e1f955835a4a8c9d24cce75b5b1f73
work_keys_str_mv	AT liucw polymericnanoparticlesconjugateanovelheptapeptideasanepidermalgrowthfactorreceptoractivetargetingligandfordoxorubicin AT linwj polymericnanoparticlesconjugateanovelheptapeptideasanepidermalgrowthfactorreceptoractivetargetingligandfordoxorubicin
_version_	1718402882604105728

Polymeric nanoparticles conjugate a novel heptapeptide as an epidermal growth factor receptor-active targeting ligand for doxorubicin

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