Dual Arnica montana and Ruscus aculeatus Hyaluronic Acid-Modified Nanostructured Lipid Carriers for Accelerated Wound Healing Effect

Skin wound healing involves a delicate balance between proliferation and remodelling processes, with significant therapeutic challenges. The present work aimed to investigate the capacity of hybrid lipid nanocarriers carrying a complex phytochemical profile (HA-NLC-ArnicaM and/or RuscusA extracts) to counteract the destructive action of oxidative free radicals and to accelerate wound closure induced on BJ fibroblast cells. The lipid and hybrid nanocarriers have main diameters ranging from 145 nm to 180 nm, electrokinetic potential between -45 mV and -62 mV, and entrapment efficiency of plant extracts exceeding 96%. HA-NLC-plant extracts exhibit an appropriate level of biocompatibility at concentrations < 50 µg/mL. ArnicaM wins the antioxidant contest while RuscusA proved excellent for accelerating the wound closure process. NLCs and HA-NLCs entrapping ArnicaM manifested the highest capacity to neutralise DPPH free radicals, reaching 79.4% inhibition. BJ fibroblast cells treated with HA-NLCs closed the wound more rapidly than NLCs, with cells reaching maximum wound closure efficiency when treated with 12.5 and 100 µg/mL HA-NLC-RuscusA, followed by HA-NLC-ArnicaM-RuscusA. These results facilitate the design of remarkable hybrid lipid nanocarriers, which exploit the emergence of a pharmacological phytochemical's synergy, and which could contribute to stimulating signalling pathways and promoting appropriate cellular regeneration, needed for wound healing.