Multifunctional Pluronic P123/F127 mixed polymeric micelles loaded with paclitaxel for the treatment of multidrug resistant tumors.
The aim of this study was to exploit the possibility of combination of active targeting function of folic acid by folate receptor-mediated endocytosis and overcoming multidrug resistance (MDR) by Pluronic block copolymers to promote drug delivery to MDR tumor following intravenous administration with paclitaxel (PTX) as model drug. Folic acid functionalized Pluronic P123/F127 mixed micelles encapsulating PTX (FPF-PTX) was firstly developed and tested in vitro and in vivo, while PTX-loaded Pluronic P123/F127 mixed micelles (PF-PTX) and Taxol were used as control. FPF-PTX was about 20 nm in diameter with spherical shape and high encapsulation efficiency. Cellular uptake of FPF-PTX was found to be higher than that of PF-PTX due to the folate receptor-mediated endocytosis effect. In vitro cytotoxicity, cell apoptosis and cell cycle arrest studies also revealed that FPF-PTX was more potent than those of PF-PTX and Taxol. In vivo pharmacokinetic study in rats showed that the polymeric micelles significantly enhanced the bioavailability of PTX (∼3 fold) than Taxol. Moreover, in BALB/c mice bearing KBv MDR tumor xenografts, stronger antitumor efficacy was shown in FPF-PTX group, with good correlation between in vitro and in vivo. In conclusion, folate-conjugated Pluronic micelles could be a potential vehicle for delivering hydrophobic chemotherapeutic drugs to MDR tumors.
School of Pharmacy, Fudan University, Lane 826, Zhangheng Road, Shanghai 201203, China.
Wei
W
Zhang
Yuan
Y
Shi
Yanzuo
Y
Chen
Jiang
J
Ye
Xianyi
X
Sha
Xiaoling
X
Fang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D017239:Paclitaxel / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011060:Poloxalene / Q000737:chemistry*; D011095:Polyethylenes / Q000737:chemistry*; D011126:Polypropylenes / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008823:Micelles; D011095:Polyethylenes; D011126:Polypropylenes; C464484:pluronic block copolymer P123; D011060:Poloxalene; C078661:UCON 50-HB-5100; D017239:Paclitaxel