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已发表论文
D-α-琥珀酸生育酚聚乙二醇酯衍生物纳米颗粒作为紫杉醇 (paclitaxel) 递送的新型载体
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 Pages 5219—5235
DOI http://dx.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
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
Keywords: 4-arm-PEG, TPGS, paclitaxel, nanoparticles, antitumor
