Enhanced solubility of paclitaxel using water-soluble and biocompatible 2-methacryloyloxyethyl phosphorylcholine polymers.

Abstract

The purpose of this study was to enhance the water-solubility of paclitaxel (PTX) using an amphiphilic 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer as the solubilizer. PTX is an antineoplastic drug effective for various cancers, especially for ovarian and breast cancers. However, its solubility in aqueous medium is quite low, less than 0.1 microg/mL in water. We prepared the amphiphilic MPC polymers containing hydrophobic units to form aggregates and provide hydrophobic domains in water. The most effective polymer to dissolve the PTX was poly[MPC-co-n-butyl methacrylate(BMA) (PMB30W)] with 70 mol % of the BMA unit. The inside polarity of PMB30W aggregate was the same as that of ethanol, which is a good solvent for dissolving PTX. The diameter of PMB30W aggregate containing 1 mg/mL of PTX was 50 nm in aqueous medium. The concentration of PTX in the PMB30W aqueous solution reached 5.0 mg/mL. The solution was transparent and PTX did not precipitate even when the solution was stored at room temperature for 1 month. Animal experiments indicated that the PMB30W has no adverse effect even when the polymer solution is injected into the bloodstream. From the PMB30W/PTX solution, we prepared by the solvent evaporation method a PMB30W film containing PTX with good transparency. The PMB30W film containing PTX easily dissolved in water to give a clear solution. We conclude that the water-soluble amphiphilic MPC polymers are good solubilizers for PTX as injectable and biocompatible drug formulations.