Apremilast (APL) has profound anti-inflammatory and wound healing activity, alongside other dermal care. This study aims to develop APL-loaded NEs (ANE1-ANE5) using eucalyptus oil (EO) as the oil and Tween-80 and transcutol-HP (THP) as a surfactant and co-surfactant, respectively. The prepared NEs were then evaluated based on mean droplet size (12.63 ± 1.2 nm), PDI (0.269 ± 0.012), ZP (−23.00 ± 5.86), RI (1.315 ± 0.02), and %T (99.89 ± 0.38) and ANE4 was optimized. Further, optimized NEs (ANE4) were incorporated into chitosan gel (2%, w/v). The developed ANE4-loaded chitosan gel was then evaluated for pH, spreadability, in vitro diffusion, and wound healing and anti-inflammatory studies. Moreover, in vivo studies denoted improved anti-inflammatory and wound healing activity and represented a decrease in wound size percentage (99.68 ± 0.345%) for the APNE2 gel test compared to a negative control (86.48 ± 0.87%) and standard control (92.82 ± 0.34%). Thus, the formulation of ANE4-loaded chitosan gels is an efficient topical treatment strategy for inflammatory and wound healing conditions.
