Perillaldehyde-Encapsulated Lipid Nanoparticle Hydrogel for Enhanced Wound Healing, Improved Stability and Biocompatibility

Volatile phytochemicals such as perillaldehyde (PAH) exhibit antimicrobial and anti-inflammatory activities relevant to wound repair; however, topical use is limited by volatility, chemical instability, and potential irritation associated with burst exposure. Here, we developed a nano-in-hydrogel dressing by encapsulating PAH into lipid nanoparticles (PAH-L) and incorporating them into a carbomer hydrogel (PAH-L-G). PAH-L showed a uniform nanoscale size distribution, high encapsulation efficiency, and good colloidal stability. After gel incorporation, PAH-L-G formed an interconnected porous network with rapid swelling and a more sustained release profile than free PAH or PAH-L. Hemocompatibility and cytocompatibility assays indicated low hemolysis and high fibroblast viability. In a full-thickness rat wound model, PAH-L-G accelerated wound closure and improved histological regeneration without obvious local irritation. Overall, the lipid-nanoparticle-in-hydrogel strategy stabilizes PAH and enables controlled topical delivery, supporting PAH-L-G as a promising wound dressing platform.