In vitro and in vivo evaluation of crosslinked wound dressing loaded with combined rosuvastatin calcium and levofoxacin simultaneously determined by eco-friendly spectrophotometric method

Abstract

Background Wound healing is a natural but complex process that can be delayed by infection. Rosuvastatin calcium (RVS) is an anti-hyperlipidemic that was recently reported to have a wound healing capability. The study aimed to investigate the impact of combining RVS with Levofloxacin (LV) on wound healing. A physically crosslinked polyvinyl alcohol (PVA) film loaded with RVS and LV was formulated as wound dressing. Formulation optimization was carried out using Box–Behnken design. The effect of independent variables (PVA and propylene glycol concentrations and the number of freeze–thaw cycles) on tensile strength (TS), elongation to break (%EB) and in vitro drugs’ release was studied. For simultaneous RVS and LV quantification in the formulations and pure form, three spectrophotometric methods: derivative of ratio spectrophotometry, first derivative and mean centering, were developed. Also, their greenness was evaluated by the Analytical Eco-Scale and the Green Analytical Procedure Index. Then, the wound healing effect of the optimized wound dressing was evaluated in rat models. Results The optimized dressing had sufficient mechanical strength (9.45 ± 0.67 MPa), adequate flexibility (112.6 ± 3.8% EB) and suitable drug release (52.3 ± 1.4% for LV and 38.99 ± 1.6% for RVS after 12 h). The proposed methods were validated following ICH guidelines, and greenness assessment suggested their very low environmental effect. The wound healing evaluation showed a higher wound contraction percentage when RVS was combined to LV. A histopathological study confirmed marked improvement in animals treated with combined formula with lowest inflammatory infiltration and optimum epithelialization, compared to other groups. Conclusion Study findings suggest that combined LV-RVS dressing would be a beneficial platform with potentiated wound healing capacity. Graphic abstract