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

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

Yupei Wu,1,* Qian Chu,2,* Songwei Tan,1 Xiangting Zhuang,1 Yuling Bao,1 Tingting Wu,1 Zhiping Zhang1,3,41Tongji School of Pharmacy, 2Department of Oncology, Tongji Hospital, Tongji Medical School, 3Hubei Engineering Research Center for NDDS, 4National Engineering Research Center for Nanomedicine, Hu...

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Autores principales: Wu YP, Chu Q, Tan SW, Zhuang XT, Bao YL, Wu TT, Zhang ZP
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
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Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/28bc70e252f3401d99d4a3cee517ef87
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spelling oai:doaj.org-article:28bc70e252f3401d99d4a3cee517ef872021-12-02T01:45:09ZD-α-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery1178-2013https://doaj.org/article/28bc70e252f3401d99d4a3cee517ef872015-08-01T00:00:00Zhttp://www.dovepress.com/d-alpha-tocopherol-polyethylene-glycol-succinate-based-derivative-nano-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yupei Wu,1,* Qian Chu,2,* Songwei Tan,1 Xiangting Zhuang,1 Yuling Bao,1 Tingting Wu,1 Zhiping Zhang1,3,41Tongji 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 workAbstract: 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, antitumorWu YPChu QTan SWZhuang XTBao YLWu TTZhang ZPDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 5219-5235 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Wu YP
Chu Q
Tan SW
Zhuang XT
Bao YL
Wu TT
Zhang ZP
D-α-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery
description Yupei Wu,1,* Qian Chu,2,* Songwei Tan,1 Xiangting Zhuang,1 Yuling Bao,1 Tingting Wu,1 Zhiping Zhang1,3,41Tongji 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 workAbstract: 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
format article
author Wu YP
Chu Q
Tan SW
Zhuang XT
Bao YL
Wu TT
Zhang ZP
author_facet Wu YP
Chu Q
Tan SW
Zhuang XT
Bao YL
Wu TT
Zhang ZP
author_sort Wu YP
title D-α-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery
title_short D-α-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery
title_full D-α-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery
title_fullStr D-α-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery
title_full_unstemmed D-α-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery
title_sort d-α-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/28bc70e252f3401d99d4a3cee517ef87
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