Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
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A Novel Monomethoxy Polyethylene Glycol–Polylactic Acid Polymeric Micelles with Higher Loading Capacity for Docetaxel and Well-Reconstitution Characteristics and Its Anti-metastasis Study
Yunfei LiFeifei YangWei ChenJiaoyang LiuWei HuangMingji JinZhonggao Gao
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2012 Volume 60 Issue 9 Pages 1146-1154


Docetaxel (DTX) is hydrophobic, and its available formulations (Taxotere® & Duopafei®) require Tween80 and ethanol vehicle to allow parental administration. DTX-loaded poly(D,L-lactide)-b-polyethylene glycol–methoxy (mPEG-b-PDLLA) polymeric micelle (PM) is a Tween80-free formulation of DTX, which has been extensively studied but rarely involved with industrialization issues. In this work, novel DTX-PM with improved loading capacity and well-reconsitution ability was developed. The freeze-dried DTX-PM was analyzed by HPLC, transmission electron microscopy (TEM) and dynamic light scattering (DLS) to determine the DTX loading, micelle morphology and size respectively. The in vitro cytotoxic activity of DTX-PM in 4T1 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the corresponding in vivo study was assessed in BALB/c mice bearing 4T1 tumor through intravenous administration. The DTX-loading and efficiency into the micelles were 20.74±1.23% and 93.7±1.03% respectively, which was much higher than ever reported PM. The DTX-PM was spherical with a mean particle size of 16.62±0.31 nm, which suggested that they were able to selectively accumulate in solid tumors by enhanced permeability and retention (EPR) effect. Another important characteristic of DTX-PM is the long term storage and reuses as aqueous injection solution. Many kinds of lyoprotectants were also investigated and dextrose was found to an excellent one. Compared with Duopafei®, DTX-PM showed better cytotoxicity and anti-metastasis ability against 4T1 cells in vitro and in vivo. In conclusion, DTX-PM significantly enhanced drug-loading capacity of DTX and had well-reconsitution ability, which could be a promising drug delivery system for clinic.

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© 2012 The Pharmaceutical Society of Japan
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