Endostar-loaded PEG-PLGA nanoparticles: in vitro and in vivo evaluation

Sanyuan Hu1, Yangde Zhang21Xiangya School of Medicine and 2National Hepatobiliary and Enteric Surgery Research Center, Ministry of Health, Central South University, Changsha, Hunan Province, People’s Republic of ChinaAbstract: Endostar, a novel recombinant human endostatin, which was a...

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Autores principales: Sanyuan Hu, Yangde Zhang
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Publicado: Dove Medical Press 2010
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spelling oai:doaj.org-article:5f78406eeed0402689d2e00355d3c30a2021-12-02T01:29:49ZEndostar-loaded PEG-PLGA nanoparticles: in vitro and in vivo evaluation1176-91141178-2013https://doaj.org/article/5f78406eeed0402689d2e00355d3c30a2010-11-01T00:00:00Zhttp://www.dovepress.com/endostar-loaded-peg-plga-nanoparticles-in-vitro-and-in-vivo-evaluation-a5741https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Sanyuan Hu1, Yangde Zhang21Xiangya School of Medicine and 2National Hepatobiliary and Enteric Surgery Research Center, Ministry of Health, Central South University, Changsha, Hunan Province, People’s Republic of ChinaAbstract: Endostar, a novel recombinant human endostatin, which was approved by the Chinese State Food and Drug Administration in 2005, has a broad spectrum of activity against solid tumors. In this study, we aimed to determine whether the anticancer effect of Endostar is increased by using a nanocarrier system. It is expected that the prolonged circulation of endostar will improve its anticancer activity. Endostar-loaded nanoparticles were prepared to improve controlled release of the drug in mice and rabbits, as well as its anticancer effects in mice with colon cancer. A protein release system could be exploited to act as a drug carrier. Nanoparticles were formulated from poly (ethylene glycol) modified poly (DL-lactide-co-glycolide) (PEG-PLGA) by a double emulsion technique. Physical and release characteristics of endostar-loaded nanoparticles in vitro were evaluated by transmission electron microscopy (TEM), photon correlation spectroscopy (PCS), and micro bicinchoninic acid protein assay. The pharmacokinetic parameters of endostar nanoparticles in rabbit and mice plasma were measured by enzyme-linked immunosorbent assay. Western blot was used to detect endostatin in different tissues. To study the effects of endostar-loaded nanoparticles in vivo, nude mice in which tumor cells HT-29 were implanted, were subsequently treated with endostar or endostar-loaded PEG-PLGA nanoparticles. Using TEM and PCS, endostar-loaded PEG-PLGA nanoparticles were found to have a spherical core-shell structure with a diameter of 169.56 ± 35.03 nm. Drug-loading capacity was 8.22% ± 2.35% and drug encapsulation was 80.17% ± 7.83%. Compared with endostar, endostar-loaded PEG-PLGA nanoparticles had a longer elimination half-life and lower peak concentration, caused slower growth of tumor cell xenografts, and prolonged tumor doubling times. The nanoparticles changed the pharmacokinetic characteristics of endostar in mice and rabbits, thereby reinforcing anticancer activity. In conclusion, PEG-PLGA nanoparticles are a feasible carrier for endostar. Endostar-loaded PEG-PLGA nanoparticles seem to have a better anticancer effect than conventional endostar. We believe that PEG-PLGA nanoparticles are an effective carrier for protein medicines.Keywords: medical physics, biologic physics, nanoparticles  Sanyuan HuYangde ZhangDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2010, Iss default, Pp 1039-1048 (2010)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Sanyuan Hu
Yangde Zhang
Endostar-loaded PEG-PLGA nanoparticles: in vitro and in vivo evaluation
description Sanyuan Hu1, Yangde Zhang21Xiangya School of Medicine and 2National Hepatobiliary and Enteric Surgery Research Center, Ministry of Health, Central South University, Changsha, Hunan Province, People’s Republic of ChinaAbstract: Endostar, a novel recombinant human endostatin, which was approved by the Chinese State Food and Drug Administration in 2005, has a broad spectrum of activity against solid tumors. In this study, we aimed to determine whether the anticancer effect of Endostar is increased by using a nanocarrier system. It is expected that the prolonged circulation of endostar will improve its anticancer activity. Endostar-loaded nanoparticles were prepared to improve controlled release of the drug in mice and rabbits, as well as its anticancer effects in mice with colon cancer. A protein release system could be exploited to act as a drug carrier. Nanoparticles were formulated from poly (ethylene glycol) modified poly (DL-lactide-co-glycolide) (PEG-PLGA) by a double emulsion technique. Physical and release characteristics of endostar-loaded nanoparticles in vitro were evaluated by transmission electron microscopy (TEM), photon correlation spectroscopy (PCS), and micro bicinchoninic acid protein assay. The pharmacokinetic parameters of endostar nanoparticles in rabbit and mice plasma were measured by enzyme-linked immunosorbent assay. Western blot was used to detect endostatin in different tissues. To study the effects of endostar-loaded nanoparticles in vivo, nude mice in which tumor cells HT-29 were implanted, were subsequently treated with endostar or endostar-loaded PEG-PLGA nanoparticles. Using TEM and PCS, endostar-loaded PEG-PLGA nanoparticles were found to have a spherical core-shell structure with a diameter of 169.56 ± 35.03 nm. Drug-loading capacity was 8.22% ± 2.35% and drug encapsulation was 80.17% ± 7.83%. Compared with endostar, endostar-loaded PEG-PLGA nanoparticles had a longer elimination half-life and lower peak concentration, caused slower growth of tumor cell xenografts, and prolonged tumor doubling times. The nanoparticles changed the pharmacokinetic characteristics of endostar in mice and rabbits, thereby reinforcing anticancer activity. In conclusion, PEG-PLGA nanoparticles are a feasible carrier for endostar. Endostar-loaded PEG-PLGA nanoparticles seem to have a better anticancer effect than conventional endostar. We believe that PEG-PLGA nanoparticles are an effective carrier for protein medicines.Keywords: medical physics, biologic physics, nanoparticles 
format article
author Sanyuan Hu
Yangde Zhang
author_facet Sanyuan Hu
Yangde Zhang
author_sort Sanyuan Hu
title Endostar-loaded PEG-PLGA nanoparticles: in vitro and in vivo evaluation
title_short Endostar-loaded PEG-PLGA nanoparticles: in vitro and in vivo evaluation
title_full Endostar-loaded PEG-PLGA nanoparticles: in vitro and in vivo evaluation
title_fullStr Endostar-loaded PEG-PLGA nanoparticles: in vitro and in vivo evaluation
title_full_unstemmed Endostar-loaded PEG-PLGA nanoparticles: in vitro and in vivo evaluation
title_sort endostar-loaded peg-plga nanoparticles: in vitro and in vivo evaluation
publisher Dove Medical Press
publishDate 2010
url https://doaj.org/article/5f78406eeed0402689d2e00355d3c30a
work_keys_str_mv AT sanyuanhu endostarloadedpegplgananoparticlesinvitroandinvivoevaluation
AT yangdezhang endostarloadedpegplgananoparticlesinvitroandinvivoevaluation
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