Prodrug-based nano-drug delivery system for co-encapsulate paclitaxel and carboplatin for lung cancer treatment

作者

Zhang, W;Li, CZ;Shen, CW;Liu, YG;Zhao, XT;Liu, Y;Zou, DN;Gao, ZF;Yue, CW

作者单位

[Zhang, Wen; Shen, Chengwu; Zou, Dongna] Shandong Univ, Shandong Prov Hosp, Dept Pharm, Jinan, Peoples R China.;-;[Li, Changzheng; Zhao, Xiaoting; Liu, Ying] Shandong Tumor Hosp & Inst, Dept Internal Med Oncol, Jinan, Peoples R China.;-;[Liu, Yuguo] Shandong Tumor Hosp & Inst, Dept Pharm, Jinan, Peoples R China.;-;[Gao, Zhenfa] Maternal & Child Hlth Care Zaozhuang, Hosp Pharm, Dept Pharm, Zaozhuang, Peoples R China.;-;[Yue, Chunwen] Shandong Univ, Dept Pharm, Hosp 2, 247 Bei Yuan Da Jie, Jinan 250033, Peoples R China.

摘要

Context: Paclitaxel (PTX) and carboplatin (CBP) are widely used for the combined chemotherapy of non-small cell lung cancer (NSCLC). However, the development of multidrug resistance of cancer cells, as well as systemic toxic side effects resulting from nonspecific localization of anticancer drugs to non-tumor areas are major obstacles to the success of chemotherapy in treating cancers.Objective: This study aimed to engineer a prodrug-based nano-drug delivery system for co-encapsulate hydrophilic (CBP) and hydrophobic anti-tumor drugs (PTX). This system was expected to resolve the multidrug resistance cause by single drug, and the dual-drug-loaded liposome was also planned to specifically target the cancer cells without obvious influence on normal cells and tissues.Methods: In this paper, PLGA-PEG-CBP was synthesized by the conjugation between the carboxylic group of PLGA-PEG-COOH and the amino group of CBP. Then, self-assembled nanoparticles for combination delivery of PTX and PLGA-PEG-CBP (PTX/CBP NPs) were prepared by solvent displacement technique. The in vitro and in vivo anti-tumor efficacy was assessed in NCL-H460 human non-small cell lung carcinoma cell line.Results: PTX/CBP NPs achieved the highest cytotoxic effect among all formulations in vitro, as compared with single drug delivery NPs. In vivo investigation on NSCLC animal models showed that co-delivery of PTX and CBP possessed high tumor-targeting capacity and strong anti-tumor activity.Conclusions: The PTX/CBP NPs constructed in this research offers an effective strategy for targeted combinational lung cancer therapy.

关键词

VINORELBINE PLUS CISPLATIN; PHASE-III; COMBINATION THERAPY; ANTITUMOR EFFICACY; TARGETED DELIVERY; BREAST-CANCER; IN-VIVO; CELL; PLATINUM; CHEMOTHERAPY

基本信息

所属机构:西药房

归属医师: 张文邹东娜沈承武

PMID：26056720

UT：000386593400048

刊名:DRUG DELIVERY

年，卷(期):2016年23卷7期

页码：2575-2580

DOI：10.3109/10717544.2015.1035466

附件：

收录: SCIE