Poly(lactide)-poly(ethylene glycol) micelles as a carrier for griseofulvin.
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.
Pierri
E
E
Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rion 26500, Greece.
Avgoustakis
K
K
D000935:Antifungal Agents / Q000008:administration & dosage*; D004337:Drug Carriers; D006118:Griseofulvin / Q000008:administration & dosage*; D008823:Micelles; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
D000935:Antifungal Agents; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D006118:Griseofulvin; D011092:Polyethylene Glycols; C033616:poly(lactide)