Efficacy of Phlomis crinita Extract-Loaded Nanostructured Formulation in Accelerating Wound Healing

<b>Background/Objectives</b>: Recent advancements in innovative drug delivery nanosystems have significantly impacted wound healing, particularly through the incorporation of natural products. This study aimed to develop and characterize a <i>Phlomis crinita</i> extract-loaded nanostructured formulation (PCE-NF) as a topical therapy for skin wounds. <b>Methods</b>: This study involved the incorporation of <i>P. crinita</i> extract in a nanoemulsion by the high-energy emulsification method. This formulation was subjected to physicochemical and biopharmaceutical characterization, and a physical stability study over 30 days. Biocompatibility, tolerability, and irritant effects were assessed, while the wound healing potential was evaluated using in vitro skin models of fibroblasts and keratinocytes. <b>Results</b>: PCE-NF showed a homogeneous appearance with nanometric-sized spherical droplets of 212.27 nm and Newtonian behavior. This formulation showed a sustained release of its majority component (luteonin 7-(6″-acetylglucoside)), which followed a hyperbolic kinetic while showing high permeation, through healthy human skin, with 22.01 µg after 27 h. There were no cytotoxic effects of PCE-NF with improvements in skin barrier function and hydration levels. The wound healing potential of PCE-NF at 3.125 µg/mL was evidenced by enhanced cell migration and accelerated wound closure in 3T3-L1 and HaCaT cells, with values of 94.24 and 92.41%, respectively. <b>Conclusions</b>: These results suggest that this formulation could be used as an effective wound healing treatment.