Vegetable Butter-Based Nanocarriers: Do Nanoparticulation and Quercetin Loading Modulate In vitro Cellular Effects...

The need for advanced yet cost-effective topical strategies for chronic skin wounds motivated this study to evaluate nanostructured lipid carriers (NLCs) based on shea or cocoa butter. Our first goal was to compare NLCs with conventional emulsions to evaluate whether butter nanoparticulation confers biological advantages for wound-related applications. NLCs were produced by hot homogenization-sonication and characterized in terms of particle size, polydispersity, morphology, and stability. Both butter-based NLCs formed stable, monodisperse nanometric systems (size 197-240 nm, PDI < 0.2). In HaCaT keratinocytes, shea and cocoa butter-based NLCs significantly enhanced proliferation (up to 137% for shea and 127% for cocoa butter) and wound repopulation (up to 96% and 65%, respectively) compared with the respective emulsions. Our second goal was to assess the effect of quercetin (QT) incorporation in the NLCs, since oxidative stress has been related to healing difficulties. QT incorporation did not further increase proliferation or repopulation but significantly improved antioxidant protection, reducing H₂O₂-induced intracellular reactive oxygen species by up to 53-62% at 12 µg/mL QT. Shea butter-based NLCs exhibited superior biological performance, including a modest intrinsic antioxidant effect (~ 15% DPPH inhibition), probably due to endogenous lipid bioactives. QT-loaded shea butter NLCs promoted enhanced QT retention within the stratum corneum (~ 14 vs. ~ 9 µg/cm²) and dermis (~ 9 vs. ~ 3 µg/cm²) of injured porcine skin while limiting permeation. These results demonstrate that vegetable butter-based NLCs, particularly from shea butter, represent a promising wound management platform that combines intrinsic lipid bioactivity, nanoscale-mediated drug availability, and skin barrier support.