Nanostructured lipid carrier enabled delivery of levofloxacin and clove essential oil to overcome Pseudomonas aeruginosa biofilm infection in burn wounds- a synergistic approach

Conventional antibiotics struggle to completely eradicate the infection because of their ineffective penetration of biofilms. New multimodal strategy integrating antibiofilm agent with antimicrobials delivered as nanomedicine could be a powerful approach to overcome biofilm resistance. Bioactive essential oils have recently garnered great attention because of their biofilm disruption and antibiofilm activity. The present study developed an integrated functional nanostructured lipid carrier (NLCs) combining clove essential oil (CO) and levofloxacin (LFX) as model antibiotic for localized delivery as hydrogel for treatment of burn wounds infected with P. aeruginosa biofilms. In vitro cell line studies demonstrated concentration dependent uptake of LFX-CO-NLCs in human dermal fibroblasts and normal human epithelial keratinocytes, and exhibhited cytocompatibility and fibroblast migration in scratch wound assay. Crystal violet assay validated strong antibiofilm effect of LFX-CO-NLCs. The nanoparticles were able to infiltrate through P. aeruginosa biofilm and be up taken by bacterial cells as evidenced by confocal microscopy. LFX-CO-NLCs hydrogel showed appreciable textural profile and pseudoplastic behavior which facilitated topical application. In vivo burn wound in mice with P. aeruginosa infection displayed early wound closure, significantly improved infection clearance and enhanced collagen deposition and wound healing after treatment with LFX-CO-NLCs hydrogel in comparison to other treatment groups. Wounds were found to be devoid of any bacterial presence after 7 days of LFX-CO-NLCs hydrogel application. It is propounded that this industrially viable technology holds great promise as future therapeutics for chronic wound infections.