Development and Evaluation of Platanus orientalis L. Extract-Loaded Liposomes for Enhanced Wound Healing

<b>Background/Objectives</b>: Wound healing is a complex biological process influenced by inflammation, oxidative stress, and cellular regeneration. Plant-derived bioactive compounds have shown potential to accelerate tissue repair through antioxidant and anti-inflammatory mechanisms. This study aimed to develop and evaluate a <i>Platanus orientalis</i> extract-loaded liposomal formulation for potential wound-healing applications. <b>Methods</b>: Four polar extracts (P1-P4) were prepared using different solvent systems and extraction techniques and were characterized by LC-HRMS to determine their phytochemical profiles. Among the identified constituents, quercetin was consistently detected across all extracts and selected as the reference compound due to its well-known wound-healing activity. Liposomes were prepared via thin-film hydration followed by probe sonication and characterized for particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and total drug content. In vitro release, cytotoxicity, and wound-healing assays were subsequently conducted to assess performance. <b>Results</b>: The optimized liposome formulation had a mean particle size of 106.6 ± 5.4 nm, a PDI of 0.11 ± 0.04, and a zeta potential of -14.1 ± 0.5 mV. Environmental scanning electron microscopy (ESEM) confirmed the nanosized spherical morphology and homogeneous vesicle distribution, supporting the successful development of the liposomal delivery system. Encapsulation efficiency and total drug content were determined as 72.25 ± 1.05% and 96.15 ± 0.14%, respectively. In vitro release studies demonstrated a biphasic pattern with an initial burst followed by a sustained release, reaching approximately 75% cumulative quercetin release within 24 h. Physical stability testing confirmed that the optimized liposomal formulation remained physically stable at 5 ± 3 °C for at least 60 days. The optimized formulation showed no cytotoxic effects on CDD-1079Sk fibroblast cells and exhibited significantly enhanced wound closure in vitro. <b>Conclusions</b>: These findings indicate that the liposomal delivery of <i>Platanus orientalis</i> extract provides a biocompatible and sustained-release system that enhances wound-healing efficacy, supporting its potential use in advanced topical therapeutic applications.