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

Area of Science:

• Pharmaceutical Sciences
• Dermatology
• Materials Science

Background:

• Skin lipids, including ceramide, are crucial for protective and regenerative effects in transdermal formulations.
• Oleic acid (OA) acts as a penetration enhancer but can cause mild irritation.
• Nanovesicles offer drug localization and improved permeation through the skin.

Purpose of the Study:

• To prepare and characterize nanovesicles containing ceramide-2 with OA and palmitic acid (PA).
• To evaluate physicochemical properties, ex vivo skin permeation, and in vivo anti-inflammatory activity.
• To compare the novel nanovesicles with a commercial gel formulation.

Main Methods:

• Nanovesicles were formulated using ceramide-2, cholesterol, cholesteryl sulfate, and either OA or PA via the film hydration method.
• Characterization included particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency.
• Ex vivo permeation studies using human skin, pharmacokinetic analysis, and anti-inflammatory activity assessment in rats were performed.

Main Results:

• Vesicles exhibited sizes between 102-125 nm with PDI of 0.11-0.13 and negative zeta potential.
• The OV-3 formulation (containing OA) showed the highest entrapment efficiency and significantly higher drug flux (92.02 μg/cm²/h) compared to PV-1 (8.920 μg/cm²/h).
• OV-3 demonstrated superior anti-inflammatory activity, inhibiting 98.8% of edema compared to 77.36% for PV-1 at 3 hours.

Conclusions:

• Both OA and PA formulations showed comparable physical characteristics, but OA incorporation enhanced vesicle permeability.
• The ceramide component facilitates rapid traversal of the stratum corneum.
• The OV-3 formulation, containing 3% OA, exhibited optimal physical properties, enhanced permeation, and maximum anti-inflammatory efficacy.