Synergistic anti-glioma effect of a coloaded nano-drug delivery system

Huae Xu,1,* Feng Jia,2,* Pankaj Kumar Singh,3 Shu Ruan,4 Hao Zhang,5,* Xiaolin Li5 1Department of Pharmacy, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 2Department of Neurosurgery, Yancheng City No 1 People’s Hospital, The Fourth Affiliated Hospital of...

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Autores principales:	Xu H, Jia F, Singh PK, Ruan S, Zhang H, Li X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Resveratrol Temozolomide mPEG-PCL nanoparticle glioma Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0c78da85440d42efbc3514a24ffb0826
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spelling	oai:doaj.org-article:0c78da85440d42efbc3514a24ffb08262021-12-02T06:33:28ZSynergistic anti-glioma effect of a coloaded nano-drug delivery system1178-2013https://doaj.org/article/0c78da85440d42efbc3514a24ffb08262016-12-01T00:00:00Zhttps://www.dovepress.com/synergistic-anti-glioma-effect-of-a-coloaded-nano-drug-delivery-system-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Huae Xu,1,* Feng Jia,2,* Pankaj Kumar Singh,3 Shu Ruan,4 Hao Zhang,5,* Xiaolin Li5 1Department of Pharmacy, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 2Department of Neurosurgery, Yancheng City No 1 People’s Hospital, The Fourth Affiliated Hospital of Nantong Medical College, Yancheng, People’s Republic of China; 3Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 4Department of Endocrinology, Yancheng Third Hospital, The Affiliated Hospital of Southeast University Medical College, Yancheng, 5Department of Geriatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: The anti-glioma effect of temozolomide (Tem) is sometimes undermined by the emerging resistance. Recently, resveratrol (Res), herbal medicine extracted from grape seeds, has been demonstrated for its potential use in chemosensitization. In the current study, both these drugs were loaded simultaneously into nanoparticles with methoxy poly(ethylene glycol)-poly epsilon caprolactone (mPEG-PCL) as drug carriers in order to achieve better antitumor efficiency. Tem/Res-coloaded mPEG-PCL nanoparticles were constructed, characterized, and tested for antitumor effect on glioma cells by using in vitro and xenograft model system. The nanoparticle constructs were satisfactory with drug loading content (Res =~12.4%; Tem =~9.3%) and encapsulation capacity of >85% for both the drugs. In addition, the coencapsulation led to better in vitro stability of the nanoparticles than Tem-loaded nanoparticles. An in vitro uptake study demonstrated a high uptake efficiency of the nanoparticles by glioma cells. The synergistic antitumor effect against glioma cells was observed in the combinational treatment of Res and Tem. Tem/Res-coloaded nanoparticles induced higher apoptosis in U87 glioma cells as compared to cells treated by the combination of free drugs. Tem/Res-coloaded particles caused more effective inhibition of phosphor-Akt, leading to upregulation of the downstream apoptotic proteins. In addition, the in vivo study showed the superior tumor delaying effect of coloaded nanoparticles than that of free drug combination. These results suggest that Tem/Res-coloaded nanoparticles could be a potential useful chemotherapeutic formulation for glioma therapy. Keywords: resveratrol, temozolomide, synergy, mPEG-PCL, polymeric, drug deliveryXu HJia FSingh PKRuan SZhang HLi XDove Medical PressarticleResveratrolTemozolomidemPEG-PCLnanoparticlegliomaMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 29-40 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Resveratrol Temozolomide mPEG-PCL nanoparticle glioma Medicine (General) R5-920
spellingShingle	Resveratrol Temozolomide mPEG-PCL nanoparticle glioma Medicine (General) R5-920 Xu H Jia F Singh PK Ruan S Zhang H Li X Synergistic anti-glioma effect of a coloaded nano-drug delivery system
description	Huae Xu,1,* Feng Jia,2,* Pankaj Kumar Singh,3 Shu Ruan,4 Hao Zhang,5,* Xiaolin Li5 1Department of Pharmacy, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 2Department of Neurosurgery, Yancheng City No 1 People’s Hospital, The Fourth Affiliated Hospital of Nantong Medical College, Yancheng, People’s Republic of China; 3Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 4Department of Endocrinology, Yancheng Third Hospital, The Affiliated Hospital of Southeast University Medical College, Yancheng, 5Department of Geriatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: The anti-glioma effect of temozolomide (Tem) is sometimes undermined by the emerging resistance. Recently, resveratrol (Res), herbal medicine extracted from grape seeds, has been demonstrated for its potential use in chemosensitization. In the current study, both these drugs were loaded simultaneously into nanoparticles with methoxy poly(ethylene glycol)-poly epsilon caprolactone (mPEG-PCL) as drug carriers in order to achieve better antitumor efficiency. Tem/Res-coloaded mPEG-PCL nanoparticles were constructed, characterized, and tested for antitumor effect on glioma cells by using in vitro and xenograft model system. The nanoparticle constructs were satisfactory with drug loading content (Res =~12.4%; Tem =~9.3%) and encapsulation capacity of >85% for both the drugs. In addition, the coencapsulation led to better in vitro stability of the nanoparticles than Tem-loaded nanoparticles. An in vitro uptake study demonstrated a high uptake efficiency of the nanoparticles by glioma cells. The synergistic antitumor effect against glioma cells was observed in the combinational treatment of Res and Tem. Tem/Res-coloaded nanoparticles induced higher apoptosis in U87 glioma cells as compared to cells treated by the combination of free drugs. Tem/Res-coloaded particles caused more effective inhibition of phosphor-Akt, leading to upregulation of the downstream apoptotic proteins. In addition, the in vivo study showed the superior tumor delaying effect of coloaded nanoparticles than that of free drug combination. These results suggest that Tem/Res-coloaded nanoparticles could be a potential useful chemotherapeutic formulation for glioma therapy. Keywords: resveratrol, temozolomide, synergy, mPEG-PCL, polymeric, drug delivery
format	article
author	Xu H Jia F Singh PK Ruan S Zhang H Li X
author_facet	Xu H Jia F Singh PK Ruan S Zhang H Li X
author_sort	Xu H
title	Synergistic anti-glioma effect of a coloaded nano-drug delivery system
title_short	Synergistic anti-glioma effect of a coloaded nano-drug delivery system
title_full	Synergistic anti-glioma effect of a coloaded nano-drug delivery system
title_fullStr	Synergistic anti-glioma effect of a coloaded nano-drug delivery system
title_full_unstemmed	Synergistic anti-glioma effect of a coloaded nano-drug delivery system
title_sort	synergistic anti-glioma effect of a coloaded nano-drug delivery system
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/0c78da85440d42efbc3514a24ffb0826
work_keys_str_mv	AT xuh synergisticantigliomaeffectofacoloadednanodrugdeliverysystem AT jiaf synergisticantigliomaeffectofacoloadednanodrugdeliverysystem AT singhpk synergisticantigliomaeffectofacoloadednanodrugdeliverysystem AT ruans synergisticantigliomaeffectofacoloadednanodrugdeliverysystem AT zhangh synergisticantigliomaeffectofacoloadednanodrugdeliverysystem AT lix synergisticantigliomaeffectofacoloadednanodrugdeliverysystem
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Synergistic anti-glioma effect of a coloaded nano-drug delivery system

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