Adhesive nanoparticles with inflammation regulation for promoting skin flap regeneration

Local drug delivery systems have become an important field of research as locally administration of medications may overcome most of the drawbacks associated with systemic drugs. Still, to assure continuous drug release and therapeutic drug levels, keeping the delivered drug in target area remains a physiological challenge. The aim of this study was to develop novel multipotent flap-protective adhesive mangiferin (MF)-loaded liposomes (A-MF-Lip), bioinspired in mussel architecture, for the promotion of random skin flap regeneration. The long chain 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethyleneglycol)-dopamine (DSPE-PEG-DOPA) was successful combined in liposomes, being dopamine (DOPA) with terminated catechol attached at the end of chain to explore the potential ability in adherence. A-MF-Lip presented a mean particle size of 162 nm, and MF cumulative release reaching 82% up to 72 h. A-MF-Lip adhesive ability was significantly higher compared to nonadhesive mangiferin-loaded liposome (MF-Lip). Moreover, a positive effect of A-MF-Lip on cells proliferation, angiogenesis was observed. And by regulating the PPAR-gamma/NF-kappa B pathway, the A-MF-Lip established a protection effect on hypoxia induced cell apoptosis and inflammation. After locally injection delivery in a Sprague Dawley rat random skin flap model, A-MF-Lip significantly decreased flap necrosis rate and reduced flap inflammation. Therefore, A-MF-Lip is a promising multipotent flap-protective approach for random skin flap regeneration.