Wound healing is a significant healthcare problem that decreases the patient’s quality of life. Hence, several agents and approaches have been widely used to help accelerate wound healing. The challenge is to search for a topical delivery system that could supply long-acting effects, accurate doses, and rapid healing activity. Topical forms of simvastatin (SMV) are beneficial in wound care. This study aimed to develop a novel topical chitosan-based platform of SMV with folic acid (FA) for wound healing. Moreover, the synergistic effect of combinations was determined in an excisional wound model in rats. The prepared SMV-FA-loaded films (SMV-FAPFs) were examined for their physicochemical characterizations and morphology. Box-Behnken Design and response surface methodology were used to evaluate the tensile strength and release characteristics of the prepared SMV-FAPFs. Additionally, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction pattern (XRD), and animal studies were also investigated. The developed SMV-FAPFs showed a contraction of up to 80% decrease in the wound size after ten days. The results of the quantitative real-time polymerase chain reaction (RT-PCR) analysis demonstrated a significant upregulation of dermal collagen type I (CoTI) expression and downregulation of the inflammatory JAK3 expression in wounds treated with SMV-FAPFs when compared to control samples and individual drug treatments. In summary, it can be concluded that the utilization of SMV-FAPFs holds great potential for facilitating efficient and expeditious wound healing, hence presenting a feasible substitute for conventional topical administration methods.

Simvastatin (SMV) is a well-known antihyperlipidemic drug that has demonstrated wound healing effects. However, its clinical application is hindered by poor solubility. Therefore, the objective of this study was to enhance the solubility of simvastatin by utilizing various concentrations of solvents and co-solvents for formulation in selected topical dosage forms. Mixed-solvent systems, namely Buffer-methanol, Buffer-ethanol, and Buffer-dmso, were employed. Additionally, the impact of different polymer concentrations, including carboxymethyl cellulose (CMC), hydroxypropylmethyl cellulose (HPMC), and chitosan (CHT), on drug solubility was investigated.The solubility profile of SMV in 2% w/v polymeric solutions (CMC, HPMC, and CHT) was found to be 73.5, 62.1, and 59.6 µg/ml, respectively. Notably, the use of a 2% w/v chitosan solution resulted in a remarkable 50-fold increase (73.5 µg/ml) in SMV dissolution compared to its aqueous solubility (1.45 µg/ml). This significant enhancement allows for the incorporation of large amounts of the drug in formulations.Our findings indicate that the Chitosan system with ethanol exhibited the highest solubilization effect and demonstrated the necessary characteristics for the preparation and handling of wound dressing films. This suggests a promising approach for the development of topical formulations with improved solubility and potential therapeutic benefits of simvastatin.