Layer-by-layer assembled chitosan/gellan gum-based smart wound dressing for sustained mupirocin delivery and enhanced wound healing activity.

Mupirocin is a commonly used broad-spectrum topical antibiotic. However, its therapeutic applications are limited by its short half-life, necessitating frequent administration. A biopolymer-coated, layer-by-layer (LbL)-assembled mupirocin microsphere (LbL-MUP)-based wound dressing was developed to provide sustained drug release and a moist wound environment. Core alginate-based mupirocin microspheres were prepared by ionotropic gelation and sequentially LbL-coated with oppositely charged biopolymers, chitosan/gellan gum. Based on physicochemical and functional properties, F4 with chitosan/gellan gum (4:1) was considered the optimized batch. The optimized LbL-MUP formed an interconnected polymeric network, exhibiting cumulative sustained release of 91.03 ± 1.80 over 24 h. LbL-MUP exhibited a fluid uptake capacity of 477.66 ± 3.82%. These in-situ microspheres exhibited a thermosensitive transition to a high-viscosity gel at physiological temperatures, thereby effectively absorbing wound fluid. SEM micrographs of LbL-MUP showed a rougher surface than uncoated microspheres. FTIR study indicated polymer deposition; XRD and DSC revealed the amorphous nature of the formulation. LbL-MUP showed superior antimicrobial efficacy against S. aureus and Escherichia coli than mupirocin. LbL-MUP accelerated wound healing than marketed formulation, achieving 96.79 ± 2.09% wound contraction by day-21 in rats. Histopathology confirmed complete re-epithelialization and normal collagen deposition, while biomarker estimation showed TGF-β1 (926.69 ± 10.77 pg/mL) on Day-5, important for initiating wound closure. LbL-MUPs can be sprinkled onto an infected wound with minimal contact, transforming into a gel-based wound dressing that provides sustained release and maintains a moist wound environment. Thus, LbL-MUP highlights its potential as a scalable biopolymer-based formulation for the topical management of infected wounds, which may help address challenges in wound management and antimicrobial resistance.