Preparation and Characterization of the Micelle-Forming Polymeric Drug Indomethacin-lncorporated Polyfethylene oxide)-Poly(β-benzyl L-aspartate) Block Copolymer Micelles

Abstract

To estimate the feasibility of novel containers for drugs, poly(ethylene oxide)-poly(beta-benzyl L-aspartate) (PEO-PBLA) micelles were prepared by dialysis against water using different solvents. The solvent selected is very important because it drastically affects the stability of polymeric micelles. The critical micelle concentration (cmc) of the prepared micelles in distilled water was determined by a fluorescence probe technique using pyrene. Indomethacin (IMC) as a model drug was incorporated into the micelles by dialysis and an oil/water emulsion method. Characteristics of PEO-PBLA micelles without and with the physically trapped IMC in the inner core of the micelles (IMC/PEO-PBLA) were studied by dynamic light scattering and gel permeation chromatography/HPLC as well as an in vitro release test of IMC from the micelles. For the PEO-PBLA block copolymers, N,N-dimethylacetamide (DMAc) was found to be the best of the solvents tested to form stable polymeric micelles with a narrow size distribution and avoid its aggregation, and the cmc of PEO-PBLA micelles thus prepared was determined to be ca. 18 mg/L in water. The diameters of PEO-PBLA micelles and IMC/PEO-PBLA micelles in number averaged scale were observed to be ca. 19 and 25-29 nm, respectively. The release study of IMC from IMC/PEO-PBLA micelles in various buffer solutions at the pH range from 1.2 to 7.4 at 37 degrees C revealed that the release rate of IMC from the micelles was increased by increasing the pH of the medium and indicated that the release rate of IMC from the micelles are controlled by the partition coefficient of IMC based on the pH of the medium and interaction between IMC and the hydrophobic portion of the micelles.