title: D-α-tocopherol polyethylene glycol succinate-based derivative nanoparticles as a novel carrier for paclitaxel delivery.
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-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.
authors: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors: Yupei
authors: Y
authors: Wu
authors: Department of Oncology, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors: Qian
authors: Q
authors: Chu
authors: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors: Songwei
authors: S
authors: Tan
authors: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors: Xiangting
authors: X
authors: Zhuang
authors: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors: Yuling
authors: Y
authors: Bao
authors: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors: Tingting
authors: T
authors: Wu
authors: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, People's Republic of China ; Hubei Engineering Research Center for NDDS, Huazhong University of Science and Technology, Wuhan, People's Republic of China ; National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors: Zhiping
authors: Z
authors: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor / Q000187:drug effects; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D061986:MCF-7 Cells; D051379:Mice; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012509:Sarcoma / Q000188:drug therapy*; D013386:Succinates / Q000737:chemistry; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D013386:Succinates; D014810:Vitamin E; D011092:Polyethylene Glycols; C014225:tocophersolan; D017239:Paclitaxel
keywords: 4-arm-PEG; TPGS; antitumor; nanoparticles; paclitaxel