The use of nanoparticles improves the stability, solubility, and skin permeability of natural compounds in skincare products. Based on these advantages, this study aimed to incorporate the Phlomis crinita extract into polymeric nanoparticles to improve its topical skin delivery for wound healing purposes. The study involved the preparation of nanoparticles of PLGA and PLGA-PEG (PCE-PLGA-NPs and PCE-PLGA-PEG-NPs) using the solvent displacement method, physicochemical and biopharmaceutical characterization, tolerance studies by the HET-CAM assay and evaluation of skin integrity parameters, and in vitro efficacy via a scratch wound healing experiment. The prepared nanoparticles were nanometer-sized with spherical form and demonstrated an encapsulation efficiency greater than 90%. The major component (luteolin) was released following a kinetic model of hyperbola for PCE-PLGA-PEG-NPs and one-phase exponential association for PCE-PLGA-NPs. Moreover, the important permeability of luteolin skin was observed, especially for PCE-PLGA-PEG-NPs. Both formulations exhibited no irritation and no damaging effects on skin integrity, suggesting their safety. Finally, the results of the scratch wound healing experiment using 3T3-L1 cells revealed significant cell migration and proliferation, with an improved efficacy for PCE-PLGA-PEG-NPs compared to the free extract, demonstrating the potential of this formulation in the treatment of wound healing.

Background/Objectives: 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 Phlomis crinita extract-loaded nanostructured formulation (PCE-NF) as a topical therapy for skin wounds. Methods: This study involved the incorporation of P. crinita 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. Results: 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. Conclusions: These results suggest that this formulation could be used as an effective wound healing treatment.