Botanical Origin-Dependent Phytochemical Profiles and Pharmaceutical Properties of Medical-Grade Honeys: Transdermal Delivery and Antibacterial Efficacy in a Wound Fluid Model

Medical-grade honeys (MGHs) are clinically applied therapeutic agents for wound management; however, their bioactive constituent profiles and biological performance in complex wound environments remain incompletely characterized. This study evaluated the wound-healing potential, antibacterial efficacy, and transdermal penetration capacity of three commercially available MGHs: manuka (MH), chestnut (ChH), and multifloral honey (MFH). MGHs were characterized for antioxidant capacity (DPPH and ABTS), total phenolic content (TPC), and phytochemical composition by HPLC and GC-MS. Wound healing activity was assessed using a scratch assay, transdermal penetration of phenolic acids through porcine skin using Franz diffusion cells, and antibacterial efficacy by MIC assay with and without artificial wound fluid exudate. H2O2 production was quantified after 24-h incubation. All MGHs demonstrated strong antioxidant activity and high TPC, with MH and ChH showing the highest values. MH exhibited the greatest polyphenol diversity, with gallic acid predominating (101.09 µg/g), and superior transdermal penetration attributable to elevated fatty acid content. Hydrophilic phenolic acids demonstrated rapid skin penetration within 3–5 h. Wound closure capacity in the scratch assay was honey type-dependent, with ChH showing the most favorable fibroblast migratory response. ChH also exhibited the highest antibacterial activity and H2O2 generation in wound fluid exudate. MGHs exhibit distinct, botanical origin-dependent biological activities, providing a rational framework for evidence-based MGH selection in clinical wound management.