Synergistic Antitumor Efficacy Mediated by Liposomal Co-Delivery of Polymeric Micelles of Vinorelbine and Cisplatin in Non-Small Cell Lung Cancer

Shuhang Wang,1 Jingxin Gou,2 Yue Wang,1 Xinyi Tan,2 Linxuan Zhao,1 Xiangqun Jin,1 Xing Tang2 1Department of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun, 130021, Jilin, People’s Republic of China; 2Department of Pharmaceutics Science, Shenyang Pharmaceutical Uni...

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Autores principales: Wang S, Gou J, Wang Y, Tan X, Zhao L, Jin X, Tang X
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Publicado: Dove Medical Press 2021
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spelling oai:doaj.org-article:1fe338c5ba7844ffb261878f0f264a3d2021-12-02T14:17:56ZSynergistic Antitumor Efficacy Mediated by Liposomal Co-Delivery of Polymeric Micelles of Vinorelbine and Cisplatin in Non-Small Cell Lung Cancer1178-2013https://doaj.org/article/1fe338c5ba7844ffb261878f0f264a3d2021-03-01T00:00:00Zhttps://www.dovepress.com/synergistic-antitumor-efficacy-mediated-by-liposomal-co-delivery-of-po-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Shuhang Wang,1 Jingxin Gou,2 Yue Wang,1 Xinyi Tan,2 Linxuan Zhao,1 Xiangqun Jin,1 Xing Tang2 1Department of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun, 130021, Jilin, People’s Republic of China; 2Department of Pharmaceutics Science, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of ChinaCorrespondence: Xiangqun JinDepartment of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun, 130021, Jilin, People’s Republic of ChinaTel +86 431 85619252Fax +86 431 85619662Email jinxq@jlu.edu.cnPurpose: Non-small cell lung cancer (NSCLC) is an aggressive tumor with high mortality and poor prognosis. In this study, we designed a liposome encapsulating polymeric micelles (PMs) loaded with vinorelbine (NVB) and cis-diamminedichloroplatinum (II) (cisplatin or CDDP) for the treatment of NSCLC.Materials and Methods: Sodium poly(α-l-glutamic acid)-graft-methoxy-polyethylene glycol (PLG-G-PEG5K) was used to prepare NVB-loaded NVB-PMs and CDDP-loaded CDDP-PMs that were co-encapsulated into liposomes by a reverse evaporation method, yielding NVB and CDDP co-delivery liposomes (CoNP-lips) composed of egg phosphatidyl lipid-80/cholesterol/DPPG/DSPE-mPEG2000 at a molar ratio of 52:32:14:2. The CoNP-lips were characterized in terms of particle size, zeta potential, drug content, encapsulation efficiency, and structural properties. Drug release by the CoNP-lips as well as their stability and cytotoxicity was evaluated in vitro, and their antitumor efficacy was assessed in a mouse xenograft model of Lewis lung carcinoma cell-derived tumors.Results: CoNP-lips had a spherical shape with uniform size distribution; the average particle size was 162.97± 9.06 nm, and the average zeta potential was − 13.02± 0.22 mV. In vitro cytotoxicity analysis and the combination index demonstrated that the CoNP-lips achieved a synergistic cytotoxic effect at an NVB:CDDP weight ratio of 2:1 in an NSCLC cell line. There was sustained release of both drugs from CoNP-lips. The pharmacokinetic analysis showed that CoNP-lips had a higher plasma half-life than NP solution, with 6.52- and 8.03-fold larger areas under the receiver operating characteristic curves of NVB and CDDP. CoNP-lips showed antitumor efficacy in tumor-bearing C57BL/6 mice and drug accumulation in tumors via the enhanced permeability and retention effect.Conclusion: CoNP-lips are a promising formulation for targeted therapy in NSCLC.Keywords: cisplatin, vinorelbine, co-delivery liposomes, combination therapy, polymeric micelles, non-small cell lung cancerWang SGou JWang YTan XZhao LJin XTang XDove Medical Pressarticlecisplatinvinorelbineco-delivery liposomescombination therapypolymeric micellesnon-small cell lung cancerMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 2357-2372 (2021)
institution DOAJ
collection DOAJ
language EN
topic cisplatin
vinorelbine
co-delivery liposomes
combination therapy
polymeric micelles
non-small cell lung cancer
Medicine (General)
R5-920
spellingShingle cisplatin
vinorelbine
co-delivery liposomes
combination therapy
polymeric micelles
non-small cell lung cancer
Medicine (General)
R5-920
Wang S
Gou J
Wang Y
Tan X
Zhao L
Jin X
Tang X
Synergistic Antitumor Efficacy Mediated by Liposomal Co-Delivery of Polymeric Micelles of Vinorelbine and Cisplatin in Non-Small Cell Lung Cancer
description Shuhang Wang,1 Jingxin Gou,2 Yue Wang,1 Xinyi Tan,2 Linxuan Zhao,1 Xiangqun Jin,1 Xing Tang2 1Department of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun, 130021, Jilin, People’s Republic of China; 2Department of Pharmaceutics Science, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of ChinaCorrespondence: Xiangqun JinDepartment of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun, 130021, Jilin, People’s Republic of ChinaTel +86 431 85619252Fax +86 431 85619662Email jinxq@jlu.edu.cnPurpose: Non-small cell lung cancer (NSCLC) is an aggressive tumor with high mortality and poor prognosis. In this study, we designed a liposome encapsulating polymeric micelles (PMs) loaded with vinorelbine (NVB) and cis-diamminedichloroplatinum (II) (cisplatin or CDDP) for the treatment of NSCLC.Materials and Methods: Sodium poly(α-l-glutamic acid)-graft-methoxy-polyethylene glycol (PLG-G-PEG5K) was used to prepare NVB-loaded NVB-PMs and CDDP-loaded CDDP-PMs that were co-encapsulated into liposomes by a reverse evaporation method, yielding NVB and CDDP co-delivery liposomes (CoNP-lips) composed of egg phosphatidyl lipid-80/cholesterol/DPPG/DSPE-mPEG2000 at a molar ratio of 52:32:14:2. The CoNP-lips were characterized in terms of particle size, zeta potential, drug content, encapsulation efficiency, and structural properties. Drug release by the CoNP-lips as well as their stability and cytotoxicity was evaluated in vitro, and their antitumor efficacy was assessed in a mouse xenograft model of Lewis lung carcinoma cell-derived tumors.Results: CoNP-lips had a spherical shape with uniform size distribution; the average particle size was 162.97± 9.06 nm, and the average zeta potential was − 13.02± 0.22 mV. In vitro cytotoxicity analysis and the combination index demonstrated that the CoNP-lips achieved a synergistic cytotoxic effect at an NVB:CDDP weight ratio of 2:1 in an NSCLC cell line. There was sustained release of both drugs from CoNP-lips. The pharmacokinetic analysis showed that CoNP-lips had a higher plasma half-life than NP solution, with 6.52- and 8.03-fold larger areas under the receiver operating characteristic curves of NVB and CDDP. CoNP-lips showed antitumor efficacy in tumor-bearing C57BL/6 mice and drug accumulation in tumors via the enhanced permeability and retention effect.Conclusion: CoNP-lips are a promising formulation for targeted therapy in NSCLC.Keywords: cisplatin, vinorelbine, co-delivery liposomes, combination therapy, polymeric micelles, non-small cell lung cancer
format article
author Wang S
Gou J
Wang Y
Tan X
Zhao L
Jin X
Tang X
author_facet Wang S
Gou J
Wang Y
Tan X
Zhao L
Jin X
Tang X
author_sort Wang S
title Synergistic Antitumor Efficacy Mediated by Liposomal Co-Delivery of Polymeric Micelles of Vinorelbine and Cisplatin in Non-Small Cell Lung Cancer
title_short Synergistic Antitumor Efficacy Mediated by Liposomal Co-Delivery of Polymeric Micelles of Vinorelbine and Cisplatin in Non-Small Cell Lung Cancer
title_full Synergistic Antitumor Efficacy Mediated by Liposomal Co-Delivery of Polymeric Micelles of Vinorelbine and Cisplatin in Non-Small Cell Lung Cancer
title_fullStr Synergistic Antitumor Efficacy Mediated by Liposomal Co-Delivery of Polymeric Micelles of Vinorelbine and Cisplatin in Non-Small Cell Lung Cancer
title_full_unstemmed Synergistic Antitumor Efficacy Mediated by Liposomal Co-Delivery of Polymeric Micelles of Vinorelbine and Cisplatin in Non-Small Cell Lung Cancer
title_sort synergistic antitumor efficacy mediated by liposomal co-delivery of polymeric micelles of vinorelbine and cisplatin in non-small cell lung cancer
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/1fe338c5ba7844ffb261878f0f264a3d
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