The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

Chung Ping Leon Wan,* Kevin Letchford,* John K Jackson, Helen M Burt Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada*These authors contributed equally to this workAbstract: Two types of nanoparticles were prepared using the diblock copolymer methoxy poly(eth...

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Autores principales:	Wan CP, Letchford K, Jackson JK, Burt HM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/9aabe16a2e784ad6bda336f61f47fda9
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spelling	oai:doaj.org-article:9aabe16a2e784ad6bda336f61f47fda92021-12-02T07:14:14ZThe combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance1176-91141178-2013https://doaj.org/article/9aabe16a2e784ad6bda336f61f47fda92013-01-01T00:00:00Zhttp://www.dovepress.com/the-combined-use-of-paclitaxel-loaded-nanoparticles-with-a-low-molecul-a12037https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Chung Ping Leon Wan,* Kevin Letchford,* John K Jackson, Helen M Burt Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada*These authors contributed equally to this workAbstract: Two types of nanoparticles were prepared using the diblock copolymer methoxy poly(ethylene glycol)-block-poly(caprolactone) (MePEG-b-PCL), with either a short PCL block length, which forms micelles, or with a longer PCL block length, which forms kinetically &quot;frozen core&quot; structures termed nanospheres. Paclitaxel (PTX)-loaded micelles and nanospheres were evaluated for their cytotoxicity, cellular polymer uptake, and drug accumulation in drug-sensitive (Madin&ndash;Darby Canine Kidney [MDCK]II) and multidrug-resistant (MDR) P-glycoprotein (P-gp)-overexpressing (MDCKII-MDR1) cell lines. Both types of PTX-loaded nanoparticles were equally effective at inhibiting proliferation of MDCKII cells, but PTX-loaded micelles were more cytotoxic than nanospheres in MDCKII-MDR1 cells. The intracellular accumulation of both PTX and the diblock copolymers were similar for both nanoparticles, suggesting that the difference in cytotoxicity might be due to the different drug-release profiles. Furthermore, the cytotoxicity of these PTX-loaded nanoparticles was enhanced when these systems were subsequently or concurrently combined with a low-molecular-weight MePEG-b-PCL diblock copolymer, which we have previously demonstrated to be an effective P-gp inhibitor. These results suggest that the dual functionality of MePEG-b-PCL might be useful in delivering drug intracellularly and in modulating P-gp in order to optimize the cytotoxicity of PTX in multidrug-resistant cells.Keywords: multidrug resistance, paclitaxel, nanoparticles, micelles, nanospheres, P-glycoproteinWan CPLetchford KJackson JKBurt HMDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 379-391 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Wan CP Letchford K Jackson JK Burt HM The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance
description	Chung Ping Leon Wan,* Kevin Letchford,* John K Jackson, Helen M Burt Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada*These authors contributed equally to this workAbstract: Two types of nanoparticles were prepared using the diblock copolymer methoxy poly(ethylene glycol)-block-poly(caprolactone) (MePEG-b-PCL), with either a short PCL block length, which forms micelles, or with a longer PCL block length, which forms kinetically &quot;frozen core&quot; structures termed nanospheres. Paclitaxel (PTX)-loaded micelles and nanospheres were evaluated for their cytotoxicity, cellular polymer uptake, and drug accumulation in drug-sensitive (Madin&ndash;Darby Canine Kidney [MDCK]II) and multidrug-resistant (MDR) P-glycoprotein (P-gp)-overexpressing (MDCKII-MDR1) cell lines. Both types of PTX-loaded nanoparticles were equally effective at inhibiting proliferation of MDCKII cells, but PTX-loaded micelles were more cytotoxic than nanospheres in MDCKII-MDR1 cells. The intracellular accumulation of both PTX and the diblock copolymers were similar for both nanoparticles, suggesting that the difference in cytotoxicity might be due to the different drug-release profiles. Furthermore, the cytotoxicity of these PTX-loaded nanoparticles was enhanced when these systems were subsequently or concurrently combined with a low-molecular-weight MePEG-b-PCL diblock copolymer, which we have previously demonstrated to be an effective P-gp inhibitor. These results suggest that the dual functionality of MePEG-b-PCL might be useful in delivering drug intracellularly and in modulating P-gp in order to optimize the cytotoxicity of PTX in multidrug-resistant cells.Keywords: multidrug resistance, paclitaxel, nanoparticles, micelles, nanospheres, P-glycoprotein
format	article
author	Wan CP Letchford K Jackson JK Burt HM
author_facet	Wan CP Letchford K Jackson JK Burt HM
author_sort	Wan CP
title	The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance
title_short	The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance
title_full	The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance
title_fullStr	The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance
title_full_unstemmed	The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance
title_sort	combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of p-glycoprotein to overcome drug resistance
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/9aabe16a2e784ad6bda336f61f47fda9
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The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

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