Enhanced therapeutic approach for diabetic foot ulcers: comparative study and characterisation of mupirocin-loaded nanosponge gel with marketed formulation for accelerating wound healing and in vivo evaluation

Abstract

Background

The current investigation aimed to develop, optimise, and assess a mupirocin-loaded nanosponge-based topical delivery system for diabetic foot ulcer and to achieve prolonged drug release while improving drug deposition within the skin. The nanosponges carrying mupirocin were formulated using the emulsion solvent diffusion method. A 3² factorial design was utilised to investigate effect of two factors, specifically the concentration of ethyl cellulose and the stirring rate, on the physical attributes of the nanosponges. The optimised nanosponge formulation batch (F9) was subsequently incorporated into a Carbopol gel base, ensuring the desired physical attributes were achieved in the gel formulation containing nanosponges. The research included in vitro drug release evaluation, ex vivo drug deposition analysis, assessment of the antimicrobial action of the nanosponge formulation, and in vivo diabetic wound healing.

Results

Drug polymer compatibility analysis was conducted using FT-IR spectroscopy revealed no interactions among mupirocin and ethyl cellulose molecules. Further FT-IR spectroscopy, DSC spectroscopy, and XRD spectroscopy analysis of optimised formulation batch revealed that the drug was successfully entrapped in nanosponges. Scanning electron microscopy confirmed the spherical and porous nature of the prepared nanosponges. The drug release pattern across the cellulose dialysis membrane followed a diffusion-controlled release pattern, and the drug deposition analysis exhibited substantial retention of mupirocin in the skin from the nanosponges formulation for up to 24 h. Furthermore, the optimised nanosponges gel formulation demonstrated stability and non-irritant properties, as indicated by the HET-CAM test. In vivo evaluation of wound healing activity in a Streptozotocin-induced diabetes mellitus with excision wound model revealed significant actions pertaining to wound healing and closure after 16 days of treatment.

Conclusion

The mupirocin-loaded nanosponge gel contributed to remarkable and swift recovery and closure of wounds in diabetic rats. The nanosponges, acting as carriers for mupirocin, facilitated the effective delivery of the drug to the wound area, while the gel fostered an optimally humid environment conducive to wound care during the final stages of wound healing and sealing.

Graphical abstract