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A Nanomicellar Prodrug Carrier Based on Ibuprofen-Conjugated Polymer for Co-delivery of Doxorubicin.

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机构: [1]Department of Pharmacy, The Third Xiangya Hospital of Central South University, Changsha, China [2]State Key Laboratory of Powder Metallurgy, Department of Pharmaceutical Sciences, School of Pharmacy, Central South University, Changsha, China [3]Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, United States [4]Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, China [5]Guangdong Second Provincial General Hospital, Guangzhou, China [6]School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
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关键词: ibuprofen nanomicellar prodrug carrier doxorubicin co-delivery

摘要:
Ibuprofen (IBU) is a non-steroidal anti-inflammatory drug (NSAID), which is widely used to reduce fever and treat inflammation and acute pain. Recently, its application in cancer treatment is also being explored. In this work, we synthesized a well-defined IBU-based amphiphilic diblock copolymer via reversible addition fragmentation transfer (RAFT) polymerization of IBU-based vinyl monomer. The amphiphilic copolymer POEG-b-PVBIBU (denoted as POVI) was composed of a hydrophilic poly(oligo(ethylene glycol)) block and a hydrophobic IBU-bearing prodrug block, which was able to self-assemble into prodrug nanomicelles. In addition, it could serve as a carrier to co-load other drugs including doxorubicin (DOX), paclitaxel (PTX), and docetaxel (DTX). By using DOX as a model anti-cancer drug, the delivery function of POVI carrier, including the drug release, in vitro cytotoxicity, cellular uptake, and in vivo antitumor activity, was evaluated. DOX-loaded POVI micelles exhibited sustained release of DOX. Besides, DOX/POVI micelles were effectively taken up by tumor cells with an efficiency comparable to that of free DOX. Moreover, in vivo studies showed that POVI carrier itself had modest antitumor activity. After loading DOX, the antitumor activity was significantly increased, which was significantly higher than that of free DOX. Our results suggest that POVI polymer represents a simple and effective dual-functional carrier for co-delivery of IBU and DOX to improve the anticancer activity.

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出版当年[2017]版:
大类 | 2 区 医学
小类 | 2 区 药学
最新[2025]版:
大类 | 3 区 医学
小类 | 3 区 药学
第一作者:
第一作者机构: [1]Department of Pharmacy, The Third Xiangya Hospital of Central South University, Changsha, China [2]State Key Laboratory of Powder Metallurgy, Department of Pharmaceutical Sciences, School of Pharmacy, Central South University, Changsha, China
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