Poloxamer 407/TPGS mixed micelles for delivery of gambogic acid to breast and multidrug-resistant cancer

Vipin Saxena, M Delwar HussainDepartment of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&amp;M Health Science Center, Kingsville, TX, USABackground: Delivery of a high concentration of anticancer drugs specifically to cancer cells remains the biggest challenge for...

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Autores principales:	Hussain MD, Saxena V
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8d0f550ffb3d4a19b668fb2924ee1344
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spelling	oai:doaj.org-article:8d0f550ffb3d4a19b668fb2924ee13442021-12-02T02:10:27ZPoloxamer 407/TPGS mixed micelles for delivery of gambogic acid to breast and multidrug-resistant cancer1176-91141178-2013https://doaj.org/article/8d0f550ffb3d4a19b668fb2924ee13442012-02-01T00:00:00Zhttp://www.dovepress.com/poloxamer-407tpgs-mixed-micelles-for-delivery-of-gambogic-acid-to-brea-a9240https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Vipin Saxena, M Delwar HussainDepartment of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&amp;M Health Science Center, Kingsville, TX, USABackground: Delivery of a high concentration of anticancer drugs specifically to cancer cells remains the biggest challenge for the treatment of multidrug-resistant cancer. Poloxamers and D-&alpha;-Tocopheryl polyethylene glycol 1000 succinate (TPGS) are known inhibitors of P-glycoprotein (P-gp). Mixed micelles prepared from Poloxamer 407 and TPGS may increase the therapeutic efficacy of the drug by delivering high concentrations inside the cells and inhibiting P-gp. Gambogic acid (GA) is a naturally derived novel anticancer agent, but poor solubility and toxic side effects limit its use. In this study, we have developed Poloxamer 407 and TPGS mixed micelle-encapsulating GA for the treatment of breast and multidrug-resistant cancer.Methods: GA-loaded Poloxamer 407/TPGS mixed micelles were prepared using a thin film hydration method, and their physicochemical properties were characterized. Cellular accumulation and cytotoxicity of the GA-loaded Poloxamer 407/TPGS mixed micelles were studied in breast cancer cells, MCF-7 cells, and multidrug-resistant NCI/ADR-RES cells.Results: The diameter of GA-loaded Poloxamer 407/TPGS mixed micelles was about 17.4 &plusmn; 0.5 nm and the zeta potential -13.57 mV. The entrapment efficiency of GA was 93.1% &plusmn; 0.5% and drug loading was about 9.38% &plusmn; 0.29%. Differential scanning calorimetry and X-ray powder diffraction studies confirmed that GA is encapsulated by the polymers. The in vitro release studies showed that mixed micelles sustained the release of GA for more than 4 days. Results from cellular uptake studies indicated that GA-loaded Poloxamer 407/TPGS mixed micelles had increased cellular uptake of GA in NCI/ADR-RES cells. Cytotoxicity of GA-loaded Poloxamer 407/TPGS mixed micelles was found to be 2.9 times higher in multidrug-resistant NCI/ADR-RES cells, and 1.6 times higher in MCF-7 cells, as compared with unencapsulated GA.Conclusion: This study suggests that Poloxamer 407/TPGS mixed micelles can be used as a delivery system for GA to treat breast and multidrug-resistant cancer.Keywords: gambogic acid, Poloxamer 407, TPGS, P-glycoprotein, multidrug resistance, breast cancerHussain MDSaxena VDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 713-721 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Hussain MD Saxena V Poloxamer 407/TPGS mixed micelles for delivery of gambogic acid to breast and multidrug-resistant cancer
description	Vipin Saxena, M Delwar HussainDepartment of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&amp;M Health Science Center, Kingsville, TX, USABackground: Delivery of a high concentration of anticancer drugs specifically to cancer cells remains the biggest challenge for the treatment of multidrug-resistant cancer. Poloxamers and D-&alpha;-Tocopheryl polyethylene glycol 1000 succinate (TPGS) are known inhibitors of P-glycoprotein (P-gp). Mixed micelles prepared from Poloxamer 407 and TPGS may increase the therapeutic efficacy of the drug by delivering high concentrations inside the cells and inhibiting P-gp. Gambogic acid (GA) is a naturally derived novel anticancer agent, but poor solubility and toxic side effects limit its use. In this study, we have developed Poloxamer 407 and TPGS mixed micelle-encapsulating GA for the treatment of breast and multidrug-resistant cancer.Methods: GA-loaded Poloxamer 407/TPGS mixed micelles were prepared using a thin film hydration method, and their physicochemical properties were characterized. Cellular accumulation and cytotoxicity of the GA-loaded Poloxamer 407/TPGS mixed micelles were studied in breast cancer cells, MCF-7 cells, and multidrug-resistant NCI/ADR-RES cells.Results: The diameter of GA-loaded Poloxamer 407/TPGS mixed micelles was about 17.4 &plusmn; 0.5 nm and the zeta potential -13.57 mV. The entrapment efficiency of GA was 93.1% &plusmn; 0.5% and drug loading was about 9.38% &plusmn; 0.29%. Differential scanning calorimetry and X-ray powder diffraction studies confirmed that GA is encapsulated by the polymers. The in vitro release studies showed that mixed micelles sustained the release of GA for more than 4 days. Results from cellular uptake studies indicated that GA-loaded Poloxamer 407/TPGS mixed micelles had increased cellular uptake of GA in NCI/ADR-RES cells. Cytotoxicity of GA-loaded Poloxamer 407/TPGS mixed micelles was found to be 2.9 times higher in multidrug-resistant NCI/ADR-RES cells, and 1.6 times higher in MCF-7 cells, as compared with unencapsulated GA.Conclusion: This study suggests that Poloxamer 407/TPGS mixed micelles can be used as a delivery system for GA to treat breast and multidrug-resistant cancer.Keywords: gambogic acid, Poloxamer 407, TPGS, P-glycoprotein, multidrug resistance, breast cancer
format	article
author	Hussain MD Saxena V
author_facet	Hussain MD Saxena V
author_sort	Hussain MD
title	Poloxamer 407/TPGS mixed micelles for delivery of gambogic acid to breast and multidrug-resistant cancer
title_short	Poloxamer 407/TPGS mixed micelles for delivery of gambogic acid to breast and multidrug-resistant cancer
title_full	Poloxamer 407/TPGS mixed micelles for delivery of gambogic acid to breast and multidrug-resistant cancer
title_fullStr	Poloxamer 407/TPGS mixed micelles for delivery of gambogic acid to breast and multidrug-resistant cancer
title_full_unstemmed	Poloxamer 407/TPGS mixed micelles for delivery of gambogic acid to breast and multidrug-resistant cancer
title_sort	poloxamer 407/tpgs mixed micelles for delivery of gambogic acid to breast and multidrug-resistant cancer
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/8d0f550ffb3d4a19b668fb2924ee1344
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Poloxamer 407/TPGS mixed micelles for delivery of gambogic acid to breast and multidrug-resistant cancer

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