Abstract
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.
Highlights
The clinical applications of many antitumor drugs, such as doxorubicin (DOX), paclitaxel (PTX), and docetaxel (DTX), were limited by their low water solubility, poor bioavailability, and high toxic side effects (Lee et al, 2011; Senevirathne et al, 2016)
The macro-chain transfer agent POEG macroCTA was synthesized by reversible addition fragmentation transfer (RAFT) polymerization as previously reported (Sun et al, 2016a), which further initiated the polymerization of IBU-monomer to give the POEG-b-PVBIbu block copolymers
When we introduced vinylbenzyl group into the polymers, the drug loading capacity (DLC) was significantly improved, suggesting that, in addition to hydrophobic interaction, the π–π stacking effect between carrier and the chemotherapeutic drug may contribute to the overall DLC
Summary
The clinical applications of many antitumor drugs, such as doxorubicin (DOX), paclitaxel (PTX), and docetaxel (DTX), were limited by their low water solubility, poor bioavailability, and high toxic side effects (Lee et al, 2011; Senevirathne et al, 2016). To overcome these problems, various nanocarriers including micelles, dendrimers, and liposomes have been designed and developed for delivery of these hydrophobic antitumor drugs (Cho et al, 2008; Shen et al, 2010; Wei et al, 2013; Koudelka et al, 2015; Wang et al, 2015, 2017; Miao et al, 2017). Some bioactive compounds with special structures in the prodrug carriers could interact with the co-loaded drug via π–π stacking effect, thereby improving the drug loading capacity (DLC; Sun et al, 2017b)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
