Development and Optimization of an Apremilast-Loaded Nanoemulsion Gel for Topical Psoriasis Treatment with In Vitro Anti-Inflammatory Studies Using RAW 264.7 Cells.

Background: Apremilast (APM) is a selective phosphodiestrase-4 (PDE-4) inhibitor currently administered orally for the treatment of psoriasis. However, gastrointestinal irritation, frequent dosage regimens, and patient noncompliance limit its oral administration. Additionally, the poor permeability and solubility of APM make dermal administration challenging. Objective: The current study aims to formulate an optimized APM-loaded nanoemulsion formulation (APM-NE) to enhance drug delivery to deep psoriatic skin layers, thereby increasing dermal drug concentration for the effective treatment of psoriasis. Method: Using the phase titration method, the nanoemulsion (NE) was made with Capryol 90, Tween 20, and Labrasol as oil, surfactant, and co-surfactant, respectively. Results: The optimized formulation (F5) exhibited favorable physicochemical properties: mean droplet size of 147.4 ± 2.4 nm, and an entrapment efficiency (EE) reaching 86.30 ± 2.54%. TEM confirmed spherical, uniformly distributed droplets. In vitro release (86.1 ± 0.24%) followed zero-order kinetics. To enhance skin retention, F5 was incorporated into 2% Carbopol 980 gel, yielding F5G with pseudoplastic flow. Ex vivo permeation showed significantly higher drug delivery for F5 (1266.50 ± 5.6 µg/cm2) and F5G (1057.7 ± 6.76 µg/cm2) compared to crude APM gel (CR-APMG). In vivo, the inhibition of edema in rat paws was highest with F5G (66.83 ± 0.23%). RAW 264.7 cell studies showed 92.37% nitric oxide inhibition, and histopathology confirmed reduced inflammation. Conclusions: These results support APM-NE gel as a promising topical strategy for psoriasis therapy.