title: Paclitaxel-loaded Pluronic P123/F127 mixed polymeric micelles: formulation, optimization and in vitro characterization.
abstract: The objective of this study was to optimize and characterize a novel polymeric mixed micelle composed of Pluronic P123 and F127 loaded with paclitaxel (PTX). A Doehlert matrix design was utilized to investigate the effect of four variables, namely P123 mass fraction, amount of water, feeding of PTX and hydration temperature on the responses including drug-loading coefficient (DL %), encapsulation ratio (ER %) and the percentage of PTX precipitated from the drug-loaded mixed micelles after 48 h at 37 (PTX precipitated %) for improvement of drug solubilization efficiency and micelle stability. PTX-loaded P123/F127 mixed micelles were prepared by thin-film hydration method. The optimized formulation showed a particle size of about 25 nm with ER %>90%, and a sustained release behavior compared to Taxol. Micelle formation was confirmed by NMR spectroscopy. The mixed micelles had a low CMC of 0.0059% in water. In addition, micelle stability studies implied that introduction of Pluronic F127 (33 wt%) into P123 micelle system significantly increased the stability of PTX-loaded micelles. More importantly, in vitro cytotoxicity was assessed using human lung adenocarcinoma cell lines SPC-A1 and A-549 and was compared to Taxol and the free drug. The cell viability assay against A-549 cells exhibited the 50% inhibition concentration (IC50) of PTX-loaded P123/F127 mixed micelles (0.1 microg/ml) was much lower than those of Taxol injection (0.4 microg/ml) and the free PTX (1.7 microg/ml). Therefore, PTX-loaded P123/F127 mixed micelles may be considered as an effective anticancer drug delivery system for cancer chemotherapy.
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Wei
authors.forename: Junguo
authors.initials: J
authors.lastname: Hao
authors.forename: Shi
authors.initials: S
authors.lastname: Yuan
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Li
authors.forename: Wu
authors.initials: W
authors.lastname: Juan
authors.forename: Xianyi
authors.initials: X
authors.lastname: Sha
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Fang
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D011060:Poloxalene / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D020442:Poloxamer; C464484:pluronic block copolymer P123; D011060:Poloxalene; D017239:Paclitaxel