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Self-assembled poly(ε-caprolactone)-g-chondroitin sulfate copolymers as an intracellular doxorubicin delivery carrier against lung cancer cells

Authors Lin Y-J, Liu Y-S, Yeh H-H, Cheng T-L, Wang L-F

Received 4 May 2012

Accepted for publication 7 June 2012

Published 1 August 2012 Volume 2012:7 Pages 4169—4183

DOI https://doi.org/10.2147/IJN.S33602

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Yue-Jin Lin1, Yu-Sheng Liu,1 Hsin-Hwa Yeh,1 Tian-Lu Cheng,2 Li-Fang Wang1

1Department of Medicinal and Applied Chemistry, 2Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan

Abstract: The aim of this study was to utilize self-assembled polycaprolactone (PCL)-grafted chondroitin sulfate (CS) as an anticancer drug carrier. We separately introduced double bonds to the hydrophobic PCL and the hydrophilic CS. The modified PCL was reacted with the modified CS through a radical reaction (CSMA-g-PCL). The copolymer without doxorubicin (DOX) was noncytotoxic in CRL-5802 and NCI-H358 cells at a concentration ranging from 5–1000 µg/mL and DOX-loaded CSMA-g-PCL (Micelle DOX) had the lowest inhibitory concentration of 50% cell growth values against the NCI-H358 cells among test samples. The cellular uptake of Micelle DOX into the cells was confirmed by flow cytometric data and confocal laser scanning microscopic images. The in vivo tumor-targeting efficacy of Micelle DOX was realized using an NCI-H358 xenograft nude mouse model. The mice administered with Micelle DOX showed suppressed growth of the NCI-H358 lung tumor compared with those administered with phosphate-buffered saline and free DOX.

Keywords: chondroitin sulfate, poly(ε -caprolactone), amphiphilic copolymers, micelles, cellular uptake

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