Improving aqueous solubility and antitumor effects by nanosized gambogic acid-mPEG2000 micelles

Lulu Cai,1,* Neng Qiu,2,* Mingli Xiang,3,* Rongsheng Tong,1 Junfeng Yan,1 Lin He,1 Jianyou Shi,1 Tao Chen,4 Jiaolin Wen,3 Wenwen Wang,3 Lijuan Chen31Department of Pharmacy, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, 2College of Materials and Chemistry and C...

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Autores principales:	Cai LL, Qiu N, Xiang ML, Tong RS, Yan JF, He L, Shi JY, Chen T, Wen JL, Wang WW, Chen LJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/037ee42cd8414f31a6e97e6894ca1df5
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spelling	oai:doaj.org-article:037ee42cd8414f31a6e97e6894ca1df52021-12-02T07:22:53ZImproving aqueous solubility and antitumor effects by nanosized gambogic acid-mPEG2000 micelles1178-2013https://doaj.org/article/037ee42cd8414f31a6e97e6894ca1df52013-12-01T00:00:00Zhttp://www.dovepress.com/improving-aqueous-solubility-and-antitumor-effects-by-nanosized-gambog-a15399https://doaj.org/toc/1178-2013 Lulu Cai,1,* Neng Qiu,2,* Mingli Xiang,3,* Rongsheng Tong,1 Junfeng Yan,1 Lin He,1 Jianyou Shi,1 Tao Chen,4 Jiaolin Wen,3 Wenwen Wang,3 Lijuan Chen31Department of Pharmacy, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, 2College of Materials and Chemistry and Chemical Engineering, Chengdu University of Technology, 3State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China; 4Faculty of Pharmacy, University of Montreal, Montreal, QC, Canada *These authors contributed equally to this paperAbstract: The clinical application of gambogic acid, a natural component with promising antitumor activity, is limited due to its extremely poor aqueous solubility, short half-life in blood, and severe systemic toxicity. To solve these problems, an amphiphilic polymer-drug conjugate was prepared by attachment of low molecular weight (ie, 2 kDa) methoxy poly(ethylene glycol) methyl ether (mPEG) to gambogic acid (GA-mPEG2000) through an ester linkage and characterized by 1H nuclear magnetic resonance. The GA-mPEG2000 conjugates self-assembled to form nanosized micelles, with mean diameters of less than 50 nm, and a very narrow particle size distribution. The properties of the GA-mPEG2000 micelles, including morphology, stability, molecular modeling, and drug release profile, were evaluated. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide) tests demonstrated that the GA-mPEG2000 micelle formulation had obvious cytotoxicity to tumor cells and human umbilical vein endothelial cells. Further, GA-mPEG2000 micelles were effective in inhibiting tumor growth and prolonged survival in subcutaneous B16-F10 and C26 tumor models. Our findings suggest that GA-mPEG2000 micelles may have promising applications in tumor therapy.Keywords: gambogic acid, poly(ethylene glycol)-drug conjugate, micelle, antitumor, toxicityCai LLQiu NXiang MLTong RSYan JFHe LShi JYChen TWen JLWang WWChen LJDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 243-255 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Cai LL Qiu N Xiang ML Tong RS Yan JF He L Shi JY Chen T Wen JL Wang WW Chen LJ Improving aqueous solubility and antitumor effects by nanosized gambogic acid-mPEG2000 micelles
description	Lulu Cai,1,* Neng Qiu,2,* Mingli Xiang,3,* Rongsheng Tong,1 Junfeng Yan,1 Lin He,1 Jianyou Shi,1 Tao Chen,4 Jiaolin Wen,3 Wenwen Wang,3 Lijuan Chen31Department of Pharmacy, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, 2College of Materials and Chemistry and Chemical Engineering, Chengdu University of Technology, 3State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China; 4Faculty of Pharmacy, University of Montreal, Montreal, QC, Canada *These authors contributed equally to this paperAbstract: The clinical application of gambogic acid, a natural component with promising antitumor activity, is limited due to its extremely poor aqueous solubility, short half-life in blood, and severe systemic toxicity. To solve these problems, an amphiphilic polymer-drug conjugate was prepared by attachment of low molecular weight (ie, 2 kDa) methoxy poly(ethylene glycol) methyl ether (mPEG) to gambogic acid (GA-mPEG2000) through an ester linkage and characterized by 1H nuclear magnetic resonance. The GA-mPEG2000 conjugates self-assembled to form nanosized micelles, with mean diameters of less than 50 nm, and a very narrow particle size distribution. The properties of the GA-mPEG2000 micelles, including morphology, stability, molecular modeling, and drug release profile, were evaluated. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide) tests demonstrated that the GA-mPEG2000 micelle formulation had obvious cytotoxicity to tumor cells and human umbilical vein endothelial cells. Further, GA-mPEG2000 micelles were effective in inhibiting tumor growth and prolonged survival in subcutaneous B16-F10 and C26 tumor models. Our findings suggest that GA-mPEG2000 micelles may have promising applications in tumor therapy.Keywords: gambogic acid, poly(ethylene glycol)-drug conjugate, micelle, antitumor, toxicity
format	article
author	Cai LL Qiu N Xiang ML Tong RS Yan JF He L Shi JY Chen T Wen JL Wang WW Chen LJ
author_facet	Cai LL Qiu N Xiang ML Tong RS Yan JF He L Shi JY Chen T Wen JL Wang WW Chen LJ
author_sort	Cai LL
title	Improving aqueous solubility and antitumor effects by nanosized gambogic acid-mPEG2000 micelles
title_short	Improving aqueous solubility and antitumor effects by nanosized gambogic acid-mPEG2000 micelles
title_full	Improving aqueous solubility and antitumor effects by nanosized gambogic acid-mPEG2000 micelles
title_fullStr	Improving aqueous solubility and antitumor effects by nanosized gambogic acid-mPEG2000 micelles
title_full_unstemmed	Improving aqueous solubility and antitumor effects by nanosized gambogic acid-mPEG2000 micelles
title_sort	improving aqueous solubility and antitumor effects by nanosized gambogic acid-mpeg2000 micelles
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/037ee42cd8414f31a6e97e6894ca1df5
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Improving aqueous solubility and antitumor effects by nanosized gambogic acid-mPEG2000 micelles

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