Synergistic and complete reversal of the multidrug resistance of mitoxantrone hydrochloride by three-in-one multifunctional lipid-sodium glycocholate nanocarriers based on simultaneous BCRP and Bcl-2 inhibition

Guixia Ling,1 Tianhong Zhang,2 Peng Zhang,2 Jin Sun,1 Zhonggui He1 1Department of Pharmaceutics, 2Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China Abstract: Multidrug resistance (MDR) is a severe obstacle...

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Autores principales:	Ling G, Zhang T, Zhang P, Sun J, He Z
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Mitoxantrone hydrochloride Three-in-one multifunctional lipid-GcNa nanocarriers (TMLGNs) Sodium glycocholate Multidrug resistance Breast cancer resistance protein (BCRP) B-cell lymphoma (Bcl-2) Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a6ec154dfe03489595a25467f44f91c6
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spelling	oai:doaj.org-article:a6ec154dfe03489595a25467f44f91c62021-12-02T00:07:19ZSynergistic and complete reversal of the multidrug resistance of mitoxantrone hydrochloride by three-in-one multifunctional lipid-sodium glycocholate nanocarriers based on simultaneous BCRP and Bcl-2 inhibition1178-2013https://doaj.org/article/a6ec154dfe03489595a25467f44f91c62016-08-01T00:00:00Zhttps://www.dovepress.com/synergistic-and-complete-reversal-of-the-multidrug-resistance-of-mitox-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Guixia Ling,1 Tianhong Zhang,2 Peng Zhang,2 Jin Sun,1 Zhonggui He1 1Department of Pharmaceutics, 2Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China Abstract: Multidrug resistance (MDR) is a severe obstacle to successful chemotherapy due to its complicated nature that involves multiple mechanisms, such as drug efflux by transporters (P-glycoprotein and breast cancer resistance protein, BCRP) and anti-apoptotic defense (B-cell lymphoma, Bcl-2). To synergistically and completely reverse MDR by simultaneous inhibition of pump and non-pump cellular resistance, three-in-one multifunctional lipid-sodium glycocholate (GcNa) nanocarriers (TMLGNs) have been designed for controlled co-delivery of water-soluble cationic mitoxantrone hydrochloride (MTO), cyclosporine A (CsA – BCRP inhibitor), and GcNa (Bcl-2 inhibitor). GcNa and dextran sulfate were incorporated as anionic compounds to enhance the encapsulation efficiency of MTO (up to 97.8%±1.9%) and sustain the release of cationic MTO by electrostatic interaction. The results of a series of in vitro and in vivo investigations indicated that the TMLGNs were taken up by the resistant cancer cells by an endocytosis pathway that escaped the efflux induced by BCRP, and the simultaneous release of CsA with MTO further efficiently inhibited the efflux of the released MTO by BCRP; meanwhile GcNa induced the apoptosis process, and an associated synergistic antitumor activity and reversion of MDR were achieved because the reversal index was almost 1.0. Keywords: mitoxantrone hydrochloride, three-in-one multifunctional lipid-GcNa nanocarriers, sodium glycocholate, multidrug resistance, breast cancer resistance protein, B-cell lymphomaLing GZhang TZhang PSun JHe ZDove Medical PressarticleMitoxantrone hydrochlorideThree-in-one multifunctional lipid-GcNa nanocarriers (TMLGNs)Sodium glycocholateMultidrug resistanceBreast cancer resistance protein (BCRP)B-cell lymphoma (Bcl-2)Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 4077-4091 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mitoxantrone hydrochloride Three-in-one multifunctional lipid-GcNa nanocarriers (TMLGNs) Sodium glycocholate Multidrug resistance Breast cancer resistance protein (BCRP) B-cell lymphoma (Bcl-2) Medicine (General) R5-920
spellingShingle	Mitoxantrone hydrochloride Three-in-one multifunctional lipid-GcNa nanocarriers (TMLGNs) Sodium glycocholate Multidrug resistance Breast cancer resistance protein (BCRP) B-cell lymphoma (Bcl-2) Medicine (General) R5-920 Ling G Zhang T Zhang P Sun J He Z Synergistic and complete reversal of the multidrug resistance of mitoxantrone hydrochloride by three-in-one multifunctional lipid-sodium glycocholate nanocarriers based on simultaneous BCRP and Bcl-2 inhibition
description	Guixia Ling,1 Tianhong Zhang,2 Peng Zhang,2 Jin Sun,1 Zhonggui He1 1Department of Pharmaceutics, 2Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China Abstract: Multidrug resistance (MDR) is a severe obstacle to successful chemotherapy due to its complicated nature that involves multiple mechanisms, such as drug efflux by transporters (P-glycoprotein and breast cancer resistance protein, BCRP) and anti-apoptotic defense (B-cell lymphoma, Bcl-2). To synergistically and completely reverse MDR by simultaneous inhibition of pump and non-pump cellular resistance, three-in-one multifunctional lipid-sodium glycocholate (GcNa) nanocarriers (TMLGNs) have been designed for controlled co-delivery of water-soluble cationic mitoxantrone hydrochloride (MTO), cyclosporine A (CsA – BCRP inhibitor), and GcNa (Bcl-2 inhibitor). GcNa and dextran sulfate were incorporated as anionic compounds to enhance the encapsulation efficiency of MTO (up to 97.8%±1.9%) and sustain the release of cationic MTO by electrostatic interaction. The results of a series of in vitro and in vivo investigations indicated that the TMLGNs were taken up by the resistant cancer cells by an endocytosis pathway that escaped the efflux induced by BCRP, and the simultaneous release of CsA with MTO further efficiently inhibited the efflux of the released MTO by BCRP; meanwhile GcNa induced the apoptosis process, and an associated synergistic antitumor activity and reversion of MDR were achieved because the reversal index was almost 1.0. Keywords: mitoxantrone hydrochloride, three-in-one multifunctional lipid-GcNa nanocarriers, sodium glycocholate, multidrug resistance, breast cancer resistance protein, B-cell lymphoma
format	article
author	Ling G Zhang T Zhang P Sun J He Z
author_facet	Ling G Zhang T Zhang P Sun J He Z
author_sort	Ling G
title	Synergistic and complete reversal of the multidrug resistance of mitoxantrone hydrochloride by three-in-one multifunctional lipid-sodium glycocholate nanocarriers based on simultaneous BCRP and Bcl-2 inhibition
title_short	Synergistic and complete reversal of the multidrug resistance of mitoxantrone hydrochloride by three-in-one multifunctional lipid-sodium glycocholate nanocarriers based on simultaneous BCRP and Bcl-2 inhibition
title_full	Synergistic and complete reversal of the multidrug resistance of mitoxantrone hydrochloride by three-in-one multifunctional lipid-sodium glycocholate nanocarriers based on simultaneous BCRP and Bcl-2 inhibition
title_fullStr	Synergistic and complete reversal of the multidrug resistance of mitoxantrone hydrochloride by three-in-one multifunctional lipid-sodium glycocholate nanocarriers based on simultaneous BCRP and Bcl-2 inhibition
title_full_unstemmed	Synergistic and complete reversal of the multidrug resistance of mitoxantrone hydrochloride by three-in-one multifunctional lipid-sodium glycocholate nanocarriers based on simultaneous BCRP and Bcl-2 inhibition
title_sort	synergistic and complete reversal of the multidrug resistance of mitoxantrone hydrochloride by three-in-one multifunctional lipid-sodium glycocholate nanocarriers based on simultaneous bcrp and bcl-2 inhibition
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/a6ec154dfe03489595a25467f44f91c6
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Synergistic and complete reversal of the multidrug resistance of mitoxantrone hydrochloride by three-in-one multifunctional lipid-sodium glycocholate nanocarriers based on simultaneous BCRP and Bcl-2 inhibition

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