Advanced Hybrid Polysaccharide—Lipid Nanocarriers for Bioactivity Improvement of Phytochemicals from Centella asiatica and Hypericum perforatum

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Background/Objectives: Phytochemicals are known to be active contributors to a healthy life, providing valuable wound healing benefits. Methods: This research took an innovative approach that successfully overcame the bioavailability limits of herbal extracts, by entrapping CentellaA with HypericumP in nanostructured lipid carriers (NLCs) and hybrid hyaluronic acid (HA-NLCs) as valuable formulations with enhanced bioactivity. Results: NLCs and HA-NLCs showed excellent entrapping efficiency values for CentellaA and HypericumP ranging from 89.5 to 95.3%. Co-entrapping of CentellaA:HypericumP in a weight ratio of 4:1 and 2:1 led to diameters of 221.4 ± 2.08 nm for NLC-CentellaA-HypericumP and 220.3 ± 1.74 nm for hybrid HA-NLC-CentellaA-HypericumP. The bimodal calorimetric profile of NLCs contributed to a lower degree of lipid core structural organization. HA-NLC-CentellaA showed the safest biocompatibility behavior with BJ skin cells. Conclusions: The cells treated with NLC-CentellaA exhibited a favorable scratch wound closure and promoted the fastest BJ cell migration. NLC- and HA-NLC herbal extracts remodeled the cytoskeleton of BJ fibroblast cells. The morphological fluorescence changes revealed that the fibroblast cells retained intact their cytoskeleton, characteristic of a viable cell with no obvious stress. An active motility of cells treated with NLCs in the wound area was detected, indicating strong pro-migratory properties; e.g., for NLC-CentellaA, the wound was almost closed after 30 h. Designing NLCs with HA adaptability to reinforce the skin wound healing action represents a desired step for the development of herbal products that meets the challenge of combining the benefits of phytochemicals and nanotechnology to create value-added herbal products.