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Folate-targeted docetaxel-lipid-based-nanosuspensions for active-targeted cancer therapy

Authors Wang L, Li M, Zhang N

Received 1 April 2012

Accepted for publication 17 May 2012

Published 29 June 2012 Volume 2012:7 Pages 3281—3294

DOI https://doi.org/10.2147/IJN.S32520

Review by Single-blind

Peer reviewer comments 3

Lili Wang, Min Li, Na Zhang

School of Pharmaceutical Science, Shandong University, Jinan, Shandong, China

Abstract: The purpose of this study was to develop two novel drug delivery systems based on biodegradable docetaxel-lipid-based-nanosuspensions. The first one was poly(ethylene glycol)-modified docetaxel-lipid-based-nanosuspensions (pLNS). It was developed to increase the cycle time of the drug within the body and enhance the accumulation of the drug at the tumor site. The second one was targeted docetaxel-lipid-based-nanosuspensions (tLNS) using folate as the target ligand. The tLNS could target the tumor cells that overexpressed folate receptor (FR). The morphology, particle size, and zeta potential of pLNS and tLNS were characterized, respectively. The in vitro cytotoxicity evaluation of Duopafei®, pLNS, and tLNS were performed in human hepatocellular liver carcinoma HepG2 (FR-) and B16 (FR+) cells, respectively. The in vivo antitumor efficacy and pharmacokinetics, as well as the drug tissue distribution, were evaluated in Kunming mice bearing B16 cells. The particle size of pLNS was 204.2 ± 6.18 nm and tLNS had a mean particle size of 220.6 ± 9.54 nm. Cytotoxicity of tLNS against B16 (FR+) cell lines was superior to pLNS (P < 0.05), while there was no significant difference in the half maximum inhibitory concentration values for HepG2 (FR-) cells between pLNS and tLNS. The results of the in vivo antitumor efficacy evaluation showed that tLNS exhibited higher antitumor efficacy by reducing tumor volume (P < 0.01) compared with Duopafei and pLNS, respectively. The results of the in vivo biodistribution study indicate that the better antitumor efficacy of tLNS was attributed to the increased accumulation of the drug in the tumor.

Keywords: lipid-based-nanosuspensions, docetaxel, cancer therapy, folate, target drug delivery

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