Patches containing quercetin microcapsules to ameliorate dermal herpes simplex virus injuries in mice

This study aimed to develop patches containing quercetin-loaded microcapsules and to evaluate their in vitro and in vivo safety and efficacy in preclinical surveys. A set of in vitro experiments evidenced the virucidal activity of quercetin against the HSV-1-KOS (sensitive to acyclovir) and HSV-1-AR (resistant to acyclovir) strains, with improved outcomes upon the first. The patches presented a homogeneous aspect, were easily handled, had a suitable bioadhesion, and possessed mechanical properties of soft and weak material, besides a pH compatible with human skin. The in vitro release profile of quercetin showed an initial burst release, followed by a controlled release rate, which was best described by Gompertz kinetics (R² of 0.93). Using quercetin-loaded patches for treating HSV-1-KOS-induced injuries was feasible since they were well tolerated in the in vivo skin irritation test and significantly decreased the injury scores until the fourth out of eight days of treatment in mice compared to acyclovir cream (50 mg/g). Altogether, the in vitro and in vivo antiviral assays indicate that this flavonol acts in the earlier stage of the infection, likely impairing the HSV-1 adsorption to the cell. The anti-inflammatory capacity of the quercetin-loaded patches was noteworthy as evidenced by histological analysis. These findings bring prospects for safer and more effective management of mucocutaneous HSV-1 injuries.