Polysaccharide-Structured Nanoemulgel Matrix Regulates the Co-delivery, Retention, and Biointerface Activity of Amino-Acid-Based Therapeutics in Infected Wound Environments.

This study presents a dual-drug water-in-oil (W/O) nanoemulsion developed to encapsulate L-ascorbic acid (AA) and L-lysine (L), enhancing skin regeneration and antimicrobial efficacy. The optimized AA L W/O nanoemulsion has a droplet size of ∼150 nm, a low polydispersity index (<0.35), and a stable zeta potential, with no phase separation during 6 months of accelerated and real-time stability tests. Both AA and L exhibited high encapsulation efficiencies of 94.63 ± 0.38% and 91 ± 0.45%, respectively, which increased further upon incorporation into a tragacanth-based nanoemulgel (97.75 ± 0.91% for AA and 95.13 ± 1.75% for L), due to reduced interfacial drug leakage and enhanced entrapment in the gel matrix. The formulated nanoemulgel significantly decreased bacterial viability and disrupted biofilm, confirmed by crystal violet quantification and FE-SEM imaging. Biological evaluations revealed that the formulated nanoemulgel was noncytotoxic to HaCaT keratinocytes and significantly promoted in vitro wound closure. Overall, this study demonstrates that the codelivery of L-ascorbic acid and L-lysine within a biopolymer-stabilized W/O nanoemulgel can eliminate mono- and dual-species wound biofilms while promoting keratinocyte viability and wound closure.