Background: Scarring of the skin from burns, surgery, and injury affects the multiple functions of this organ, representing a major burden on the healthcare system and requiring the development of effective scar prevention tools, assuring wound closure without tension, while avoiding infection and wound breakdown (1). Hydrogel-based drug delivery systems are a promising novel approach for the prolonged delivery of actives. Results on topical and transdermal applications of cannabidiol (CBD) and hyaluronic acid (HA) indicate a strong reducing effect on scarring, controlling hydration during wound repair, regulating the inflammatory process, facilitating keratinocyte cells proliferation and migration, as well as the diffusion of nutritional supplies.

Methods: Preparation of lipid carriers and inclusion of actives (CBD, HA) was obtained by passive loading techniques (mechanical dispersion methods) under an inert atmosphere, the physicochemical characterization was achieved by microscopy, RMN, XRD, DLS, PDI, and Zeta potential; encapsulation efficiency by GS-MS; the cytotoxicity by MTT, Alamar Blue and LDH and the wound healing properties by DAPI on human dermal fibroblasts. The charged lipid carriers were incorporated in previously obtained hydrogels based on collagen and polycaprolactone.

Results: The CBD encapsulation was >85%. The formation of the HA complexes was confirmed by NMR spectroscopy data. The 13C NMR spectra of solid samples confirmed the stoichiometry, XRD the crystallinity nature of the CBD-loaded liposomes, with a hydrodynamic diameter of 655 nm and the PDI 0.571, which further proves the polydispersed size distribution of the samples (PDI>0.4). The zeta potential values are close to 0, indicating reduced stability and increased agglomeration tendency. Cytocompatibility rates were over 90. The collective cell migration probed by wound healing assay indicated a good pro-healing activity.

Conclusion: A novel hybrid hydrogel with scar preventive and pro-wound healing activity was developed. The hydrogel characteristics and envisioned form of application (uni-dose trans-dermal administration on site) encourage further research and provide a solid base for seeking product authorization under clinical studies.