Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan; Center for Drug Delivery Research, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address: [Email]
Phosphoester compounds are promising materials with expected biocompatibility; however, little has been reported on the use of phosphoester compounds for micelle formulations. In this study, paclitaxel (PTX)-encapsulated micelles were prepared using four kinds of alkyl di(MePEG-lactate) phosphates. From the results of the determination of critical micelle concentrations and an in vitro stability test, it was shown that a compound to which 1-eicosanol was introduced as a side chain was desirable in the preparation of PTX-encapsulated micelles (PTX-micelles). The mean volume diameter and PTX content of the micelles were 135.7 ± 52.2 nm and 3.9% ± 0.2%, respectively. in vitro release tests of the micelles were performed at different pH levels. Twenty-four hours after the start of the release test, the cumulative PTX release rate of PTX-micelles at pH 5.0 reached 96.2%, which was three times higher than that at pH 7.4. As a result of the degradation test of the compound used for the micelle, it was confirmed that this compound degraded faster at pH 5.0 than at pH 7.4. The hemolysis rate of drug-free micelles was 0.8%-1.4%, and the biocompatibility of this micelle as a drug carrier was suggested. In addition, the effectiveness of PTX-micelles in cancer treatment was evaluated via biodistribution study. PTX concentration in the tumor was significantly increased in the group administered PTX-micelles as compared with the group administered PTX solution. These results suggest that phosphoester compounds are useful in preparing biocompatible pH-responsive carriers.