Poly(lactide)-poly(ethylene glycol) micelles as a carrier for griseofulvin.

Abstract

In this work, the feasibility to develop micelle carriers of griseofulvin based on PLA-PEG copolymers was investigated. With the use of the dialysis method of micelle formation, the micellization behavior of a range of PLA(X)-PEG(5) copolymers was investigated. At copolymer concentrations in the organic solvent 10-20 mg/mL, stable micelles with 100% yield could only be prepared from PLA(X)-PEG(5) copolymers with molar composition in the range 50-70% PEG. The copolymers exhibited sufficiently low CMC to provide stable micelles in vivo. The loading capacity of PLA(4)-PEG(5) micelles with griseofulvin was 6.5 mg of drug/1 g of copolymer. The release of griseofulvin from the PLA-PEG micelles in vitro in phosphate-buffered saline (PBS) was sustained over 30 days. No burst effect was observed. Analysis of the release kinetics suggested that the release was erosion-controlled. The release profile was biphasic. Micelle degradation data in PBS indicated that the second phase of release was induced by copolymer degradation. The PLA-PEG micelles of griseofulvin were stable in simulated gastric and intestinal fluids for a long-enough time for oral application. Overall, the PLA-PEG micelles have suitable properties to be considered as potential oral or topical formulations of griseofulvin, provided that the drug-loading capacity of the micelles is sufficiently improved.