Chitosan-based films filled with nanoencapsulated essential oil: Physical-chemical characterization and enhanced wound healing activity

The economic burden of chronic wounds, the complexity of the process of tissue repair and the possibility of resistant bacterial infections, have triggered a significant research interest in the application of natural alternative therapies for wound healing. Biomolecules are intrinsically multi-active, as they affect multiple mechanisms involved in tissue repair phenomenon, including immunomodulatory, anti-inflammatory, cell proliferation, extra cellular matrix remodeling and angiogenesis. Chitosan features a unique combination of attributes, including intrinsic hemostatic, antimicrobial, and immunomodulatory properties, that make it an exceptional candidate for wound management, in the development of wound dressings and scaffolds. In this study, we produced nanoemulsions (NE) loaded with SFO, characterized them, and evaluated their tissue repairing properties. Dynamic light scattering (DLS) analysis confirmed the formation of a nanoemulsion with a droplet size of 21.12 ± 2.31 nm and a polydispersity index (PdI) of 0.159, indicating good stability for up to 90 days. To investigate the potential wound healing effects, SFO-loaded NE were applied on male C57BL/6 mice for seven consecutive days, producing a significantly higher wound closure efficiency (p < 0.05) for the group treated with SFO-loaded NE compared to the control group treated with the saline solution. This finding indicates that the SFO-loaded NE exhibits therapeutic properties that effectively promote wound healing in this experimental model. Then, SFO-loaded NE were incorporated into chitosan:polyvinyl alcohol (PVA)-based films. The inclusion of NE into the polymer matrix resulted in increased lipophilicity reflected by the contact angle results, while decreasing moisture absorption, water solubility, and crystallinity. Moreover, FTIR analysis confirmed the formation of new bonds between SFO-NE and the film matrix, which also impacted on porosity properties. Thermal analysis indicated a decrease in the glass transition temperature of the films due to the presence of SFO-NE, suggesting a plasticizing role of NE, confirmed by XRD results, that showed a decrease in the crystallinity of the blend films upon the addition of SFO-NE. AFM images showed no evidence of NE droplet aggregation in the Chitosan:PVA film matrix. Moisture absorption and water content decreased upon incorporation of SFO-loaded NE. Although the inclusion of NE increased hydrophobicity and water contact angle, the values remained within an acceptable range for wound healing applications. Overall, our results emphasize the significant tissue repairing properties of SFO-loaded NE and the potential of Chitosan:PVA films containing nanoencapsulated SFO as effective formulations for wound healing with notable tissue repairing properties.