Ceramide-2 nanovesicles for effective transdermal delivery: development, characterization and pharmacokinetic evaluation

Context: The vesicles based on skin lipid have a drug localization effect and its main lipid, ceramide provides protective and regenerative effects while oleic acid (OA) is a penetration enhancer, however, it causes slight irritation, so we have formulated formulation incorporating both of these to develop a transdermal formulation for better permeation. Objective: Present study investigated the preparation and characterization of physicochemical properties and permeation of nanovesicles of ceramide-2 containing OA and palmitic acid (PA) respectively and a commercial gel. Materials and methods: The vesicles were made using ceramide 2, cholesterol (Chol), cholesteryl sulfate (CS) and OA or PA, respectively, using film hydration method. The vesicles were characterized for physicochemical properties, ex vivo permeation using human skin and pharmacokinetic parameters and anti-inflammatory activity in rats. Results: The vesicles showed size at 102-125nm while PDI was 0.11-0.13 and negative zeta potential. OV-3 showed highest entrapment efficiency. The drug fluxes were 92.02 and 8.920 mu g/cm(2)/h, respectively, for OV-3 and PV-1. The C-max were 7.91 and 4.01 mu g/ml at 4 and 6 h for OV-3 (2.5 mg) and PV-1 (10 mg), respectively. OV-3 and PV-1 showed 98.8% and 77.36% edema inhibition, respectively, at 3 h. Discussion: Both formulations showed similar physical parameters and different permeation since OA get incorporated in vesicles and increases its permeability and ceramide makes sure that vesicles can rapidly traverse the stratum corneum. Conclusion: OV-3 containing 3% OA showed optimum physical parameters and good permeation with maximum anti-inflammatory activity.