Microemulsions vs chitosan derivative-coated microemulsions for dermal delivery of 8-methoxypsoralen.

BACKGROUND: 8-methoxypsoralen (8-MOP) is one of the most commonly utilized drugs in psoralen-ultraviolet A therapy for treatment of vitiligo. However, poor skin retention and systemic side effects limit the clinical application of 8-MOP. METHODS: Microemulsions (MEs) and chitosan derivative-coated 8-MOP MEs were developed and compared for dermal delivery of 8-MOP. Ex vivo skin retention/permeation study was performed to select the ME formulation with the highest retention:permeation ratio. Four different chitosan-coated MEs were prepared and compared with the ME formulation for their ability to distribute 8-MOP in the skin. RESULTS: Among various ME formulations developed, a formulation containing 2.9% ethyl oleate, 17.2% Cromophor EL35, 8.6% ethanol and 71.3% water showed the highest ex vivo skin retention:permeation ratio (1.98). Of four chitosan-coated MEs prepared, carboxymethyl chitosan-coated MEs (CC-MEs) and hydroxypropyl chitosan-coated MEs (HC-MEs) showed higher ex vivo skin retention:permeation ratio (1.46 and 1.84). and were selected for in vivo pharmacokinetic study. AUC(skin) (0-12 h) for 8-MOP MEs (4578.56 h·ng·mL(-1)) was higher than HC-MEs (3422.47 h·ng·mL(-1)), CC-MEs (2808.51 h·ng·mL(-1)) and tincture (1500.16 h·ng·mL(-1)). Also, AUCplasma (0-12 h) for MEs (39.35±13.90 h·ng·mL(-1)) was significantly lower than HC-MEs (66.32 h·ng·mL(-1)), CC-MEs (59.70 h·ng·mL(-1)) and tincture (73.02 h·ng·mL(-1)). CONCLUSION: These combined results suggested that the MEs developed could be a promising and safe alternative for targeted skin delivery of 8-MOP.