Fabrication of novel polysaccharide hybrid nanoliposomes containing citral for targeting MRSA-infected wound healing

• The synthesized CMC/PA/Cit-NLPs exhibited good biocompatibility. • CMC/PA/Cit-NLPs decreased bacterial growth in a MRSA-infected excision wound model. • CMC/PA/Cit-NLPs modulated of inflammatory responses through reducing the expression levels of NF-Kb. • CMC/PA/Cit-NLPs upregulated the fibroblast cells infiltration and collagen type 1A biosynthesis. • CMC/PA/Cit-NLPs accelerated the healing of MRSA-infected excision wound model. Citral (Cit) and Carboxymethyl chitosan (CMC)/polyamide (PA) are known to have antibacterial properties and can be used for healing infected wounds, but their advantages are faced with limitations owing to their structures. Using nanoliposomes (NLPs) for covering Cit and CMC/PA is a good strategy to overcome their limitations. This study evaluates the in vitro antibacterial properties and wound healing activity of NLPs containing Cit and CMC/PA in infected full-thickness wounds in a mouse model. A facile method was used to produce Cit-NLPs, CMC/PA/NLPs, and CMC/PA/Cit-NLPs. Structural properties, in vitro, the release of Cit, in vitro antibacterial properties, and cytotoxicity were investigated. The prepared NLPs were mixed with basal ointment and used to treat the infected wounds. Wound rate, histopathological assessment by immunofluorescence staining were also investigated. A slow-release for Cit-NLPs and insignificant toxicity were found. Under in vitro conditions, NLPs showed better antibacterial activities in higher dilutions. The prepared ointments increased the expression of COL1A, IL-10 and SIRT6, and decreased the expression of NF-κB and total bacterial count compared to basal ointment ( P<0.05 ). In conclusion, the results revealed that CMC/PA/Cit-NLPs have potential as a therapy for infected full-thickness wounds and clinical studies can be suggested.