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pH-sensitive and folic acid-targeted MPEG-PHIS/FA-PEG-VE mixed micelles for the delivery of PTX-VE and their antitumor activity

Authors Di Y, Li T, Zhu Z, Chen F, Jia L, Liu W, Gai X, Wang Y, Pan W, Yang X

Received 17 May 2017

Accepted for publication 6 July 2017

Published 16 August 2017 Volume 2017:12 Pages 5863—5877

DOI https://doi.org/10.2147/IJN.S141982

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Lei Yang


Yan Di,1 Ting Li,1 Zhihong Zhu,1 Fen Chen,2 Lianqun Jia,2 Wenbing Liu,3 Xiumei Gai,1 Yingying Wang,1 Weisan Pan,1 Xinggang Yang1

1Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 2Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, 3Key Laboratory of Structure-Based Drug Design & Discovery, Shenyang Pharmaceutical University, Ministry of Education, Shenyang, China

Abstract: The aim of this study was to simultaneously introduce pH sensitivity and folic acid (FA) targeting into a micelle system to achieve quick drug release and to enhance its accumulation in tumor cells. Paclitaxel-(+)-α-tocopherol (PTX-VE)-loaded mixed micelles (PHIS/FA/PM) fabricated by poly(ethylene glycol) methyl ether-poly(histidine) (MPEG-PHIS) and folic acid-poly(ethylene glycol)-(+)-α-tocopherol (FA-PEG-VE) were characterized by dynamic light scattering and transmission electron microscopy (TEM). The mixed micelles had a spherical morphology with an average diameter of 137.0±6.70 nm and a zeta potential of -48.7±4.25 mV. The drug encapsulation and loading efficiencies were 91.06%±2.45% and 5.28%±0.30%, respectively. The pH sensitivity was confirmed by changes in particle size, critical micelle concentration, and transmittance as a function of pH. MTT assay showed that PHIS/FA/PM had higher cytotoxicity at pH 6.0 than at pH 7.4, and lower cytotoxicity in the presence of free FA. Confocal laser scanning microscope images demonstrated a time-dependent and FA-inhibited cellular uptake. In vivo imaging confirmed that the mixed micelles targeted accumulation at tumor sites and the tumor inhibition rate was 85.97%. The results proved that the mixed micelle system fabricated by MPEG-PHIS and FA-PEG-VE is a promising approach to improve antitumor efficacy.

Keywords: pH sensitive, folic acid targeting, mixed micelles, drug delivery, in vivo antitumor activity

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