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Natural medicines formulated using nanotechnology-based systems are a rich source of new wound-treating therapeutics. This study aims to develop thymol-loaded cationic polymeric nanoparticles (CPNPs) to enhance the skin retention and wound healing efficacy of thymol. The developed materials exhibited entrapment efficiencies of 56.58 to 68.97%, particle sizes of 36.30 to 99.41 nm, and positively charged zeta potential. In Vitro sustained release of thymol up to 24 h was achieved. Selected thymol CPNPs (F5 and C2) were mixed with methylcellulose to form hydrogels (GF5 and GC2). An In Vivo skin-retention study revealed that GF5 and GC2 showed 3.3- and 3.6-fold higher retention than free thymol, respectively. An In Vitro scratch-wound healing assay revealed a significant acceleration in wound closure at 24 h by 58.09% (GF5) and 57.45% (GC2). The potential for free thymol hydrogel, GF5, and GC2 to combat MRSA in a murine skin model was evaluated. The bacterial counts, recovered from skin lesions and the spleen, were assessed. Although a significant reduction in the bacterial counts recovered from the skin lesions was shown by all three formulations, only GF5 and GC2 were able to reduce the bacterial dissemination to the spleen. Thus, our study suggests that Eudragit RS30D nanoparticles-based hydrogels are a potential delivery system for enhancing thymol skin retention and wound healing activity.

Thymol-Loaded Eudragit RS30D Cationic Nanoparticles-Based Hydrogels for Topical Application in Wounds: In Vitro and In Vivo Evaluation