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

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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:International journal of nanomedicine 2015-01, Vol.10 (default), p.5219-5235
Hauptverfasser: Wu, Yupei, Chu, Qian, Tan, Songwei, Zhuang, Xiangting, Bao, Yuling, Wu, Tingting, Zhang, Zhiping
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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-PEG(5K)-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-PEG(5K)-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-PEG(5K)-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-PEG(5K)-TPGS NP may have the potential as an anticancer drug delivery system.
ISSN:1178-2013
1176-9114
1178-2013
DOI:10.2147/IJN.S82847