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D-α-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery

Authors Wu YP, Chu Q, Tan SW, Zhuang XT, Bao YL, Wu TT, Zhang ZP

Received 13 February 2015

Accepted for publication 18 May 2015

Published 20 August 2015 Volume 2015:10(1) Pages 5219—5235

DOI https://doi.org/10.2147/IJN.S82847

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 7

Editor who approved publication: Dr Lei Yang

Yupei Wu,1,* Qian Chu,2,* Songwei Tan,1 Xiangting Zhuang,1 Yuling Bao,1 Tingting Wu,1 Zhiping Zhang1,3,4

1Tongji School of Pharmacy, 2Department of Oncology, Tongji Hospital, Tongji Medical School, 3Hubei Engineering Research Center for NDDS, 4National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, People’s Republic of China

*These authors contributed equally to this work

Abstract: Paclitaxel (PTX) is one of the most effective antineoplastic drugs. Its current clinical administration Taxol® is formulated in Cremophor EL, which causes serious side effects. Nanoparticles (NP) with lower systemic toxicity and enhanced therapeutic efficiency may be an alternative formulation of the Cremophor EL-based vehicle for PTX delivery. In this study, novel amphipathic 4-arm-PEG-TPGS derivatives, the conjugation of D-α-tocopherol polyethylene glycol succinate (TPGS) and 4-arm-polyethylene glycol (4-arm-PEG) with different molecular weights, have been successfully synthesized and used as carriers for the delivery of PTX. These 4-arm-PEG-TPGS derivatives were able to self-assemble to form uniform NP with PTX encapsulation. Among them, 4-arm-PEG5K-TPGS NP exhibited the smallest particle size, highest drug-loading efficiency, negligible hemolysis rate, and high physiologic stability. Therefore, it was chosen for further in vitro and in vivo investigations. Facilitated by the effective uptake of the NP, the PTX-loaded 4-arm-PEG5K-TPGS NP showed greater cytotoxicity compared with free PTX against human ovarian cancer (A2780), non-small cell lung cancer (A549), and breast adenocarcinoma cancer (MCF-7) cells, as well as a higher apoptotic rate and a more significant cell cycle arrest effect at the G2/M phase in A2780 cells. More importantly, PTX-loaded 4-arm-PEG5K-TPGS NP resulted in a significantly improved tumor growth inhibitory effect in comparison to Taxol® in S180 sarcoma-bearing mice models. This study suggested that 4-arm-PEG5K-TPGS NP may have the potential as an anticancer drug delivery system.

Keywords: 4-arm-PEG, TPGS, paclitaxel, nanoparticles, antitumor

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