Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance

Juan Li,1 Lei Zheng,2 Rongmei Wang,1 Deqing Sun,1 Shuang Liang,3 Jing Wu,1 Yongqing Liu,1 Xiaona Tian,1 Tingting Li,4 Yang Yang,5 Leiqiang Han1 1Department of Clinical Pharmacy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, People’s Republic...

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Autores principales:	Li J, Zheng L, Wang R, Sun D, Liang S, Wu J, Liu Y, Tian X, Li T, Yang Y, Han L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	paclitaxel resistance flavokawain a sodium aescinate polymer-free nanoparticles combination therapy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/ddafda60f1194070bd6044d2b8f81a39
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spelling	oai:doaj.org-article:ddafda60f1194070bd6044d2b8f81a392021-12-02T10:26:23ZSynergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance1178-2013https://doaj.org/article/ddafda60f1194070bd6044d2b8f81a392020-08-01T00:00:00Zhttps://www.dovepress.com/synergistic-combination-of-sodium-aescinate-stabilized-polymer-free-tw-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Juan Li,1 Lei Zheng,2 Rongmei Wang,1 Deqing Sun,1 Shuang Liang,3 Jing Wu,1 Yongqing Liu,1 Xiaona Tian,1 Tingting Li,4 Yang Yang,5 Leiqiang Han1 1Department of Clinical Pharmacy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, People’s Republic of China; 2Department of Pharmacy, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250031, People’s Republic of China; 3School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People’s Republic of China; 4Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA; 5China National Center for Biotechnology Development, Beijing 100039, People’s Republic of ChinaCorrespondence: Leiqiang HanDepartment of Clinical Pharmacy, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Road, Jinan, Shandong 250033, People’s Republic of ChinaTel +86-531-85875083Fax +86-531-88962544Email hanlq007@sina.cnBackground: The development of paclitaxel (PTX) resistance seriously restricts its clinical efficacy. An attractive option for combating resistance is inhibiting the expression of P-glycoprotein (P-gp) in tumor cells. We have reported that flavokawain A (FKA) inhibited P-gp protein expression in PTX-resistant A549 (A549/T) cells, indicating that FKA combined with PTX may reverse PTX resistance. However, due to the variable pharmacokinetics of FKA and PTX, the conventional cocktail combination in clinics may cause uncertainty of treatment efficacy in vivo.Materials and Methods: To synergistically elevate the anti-cancer activity of PTX and FKA in vivo, the national medical products administration (NMPA) approved sodium aescinate (Aes) was utilized to stabilize hydrophobic PTX and FKA to form polymer-free twin like PTX-A nanoparticles (NPs) and FKA-A NPs.Results: The resulting nanoparticles prepared simply by nanoprecipitation possessed similar particle size, good stability and ultrahigh drug loadings of up to 50%. With the aid of Aes, these two drugs accumulated in tumor tissue by passive targeting and were efficiently taken up by A549/T cells; this resulted in significant suppression of tumor growth in A549/T homograft mice at a low PTX dose (2.5 mg·kg− 1). Synergistic effects and reversed PTX resistance were achieved by the combination of PTX-A NPs and FKA-A NPs by inhibiting P-gp expression in tumor cells.Conclusion: Using NMPA-approved Aes to prepare twin-like nanoparticles without introducing any new materials provides an efficient platform for combination chemotherapy and clinical translation.Keywords: paclitaxel resistance, flavokawain A, sodium aescinate, polymer-free nanoparticles, combination therapyLi JZheng LWang RSun DLiang SWu JLiu YTian XLi TYang YHan LDove Medical Pressarticlepaclitaxel resistanceflavokawain asodium aescinatepolymer-free nanoparticlescombination therapyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 5839-5853 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	paclitaxel resistance flavokawain a sodium aescinate polymer-free nanoparticles combination therapy Medicine (General) R5-920
spellingShingle	paclitaxel resistance flavokawain a sodium aescinate polymer-free nanoparticles combination therapy Medicine (General) R5-920 Li J Zheng L Wang R Sun D Liang S Wu J Liu Y Tian X Li T Yang Y Han L Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance
description	Juan Li,1 Lei Zheng,2 Rongmei Wang,1 Deqing Sun,1 Shuang Liang,3 Jing Wu,1 Yongqing Liu,1 Xiaona Tian,1 Tingting Li,4 Yang Yang,5 Leiqiang Han1 1Department of Clinical Pharmacy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, People’s Republic of China; 2Department of Pharmacy, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250031, People’s Republic of China; 3School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People’s Republic of China; 4Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA; 5China National Center for Biotechnology Development, Beijing 100039, People’s Republic of ChinaCorrespondence: Leiqiang HanDepartment of Clinical Pharmacy, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Road, Jinan, Shandong 250033, People’s Republic of ChinaTel +86-531-85875083Fax +86-531-88962544Email hanlq007@sina.cnBackground: The development of paclitaxel (PTX) resistance seriously restricts its clinical efficacy. An attractive option for combating resistance is inhibiting the expression of P-glycoprotein (P-gp) in tumor cells. We have reported that flavokawain A (FKA) inhibited P-gp protein expression in PTX-resistant A549 (A549/T) cells, indicating that FKA combined with PTX may reverse PTX resistance. However, due to the variable pharmacokinetics of FKA and PTX, the conventional cocktail combination in clinics may cause uncertainty of treatment efficacy in vivo.Materials and Methods: To synergistically elevate the anti-cancer activity of PTX and FKA in vivo, the national medical products administration (NMPA) approved sodium aescinate (Aes) was utilized to stabilize hydrophobic PTX and FKA to form polymer-free twin like PTX-A nanoparticles (NPs) and FKA-A NPs.Results: The resulting nanoparticles prepared simply by nanoprecipitation possessed similar particle size, good stability and ultrahigh drug loadings of up to 50%. With the aid of Aes, these two drugs accumulated in tumor tissue by passive targeting and were efficiently taken up by A549/T cells; this resulted in significant suppression of tumor growth in A549/T homograft mice at a low PTX dose (2.5 mg·kg− 1). Synergistic effects and reversed PTX resistance were achieved by the combination of PTX-A NPs and FKA-A NPs by inhibiting P-gp expression in tumor cells.Conclusion: Using NMPA-approved Aes to prepare twin-like nanoparticles without introducing any new materials provides an efficient platform for combination chemotherapy and clinical translation.Keywords: paclitaxel resistance, flavokawain A, sodium aescinate, polymer-free nanoparticles, combination therapy
format	article
author	Li J Zheng L Wang R Sun D Liang S Wu J Liu Y Tian X Li T Yang Y Han L
author_facet	Li J Zheng L Wang R Sun D Liang S Wu J Liu Y Tian X Li T Yang Y Han L
author_sort	Li J
title	Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance
title_short	Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance
title_full	Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance
title_fullStr	Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance
title_full_unstemmed	Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance
title_sort	synergistic combination of sodium aescinate-stabilized, polymer-free, twin-like nanoparticles to reverse paclitaxel resistance
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/ddafda60f1194070bd6044d2b8f81a39
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Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance

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