Niosomes modified with a novel pH-responsive coating (mPEG-OA) enhance the antibacterial and anti-biofilm activity of vancomycin against methicillin-resistant Staphylococcus aureus

Surface functionalization of nanoparticles has shown potential in enhancing the efficacy of antibiotic-loaded nanosystems against drug-resistant bacteria. The objective of this study was to synthesize and characterize an acid-cleavable pH-responsive polymer from methoxy polyethylene glycol and oleylamine (mPEG-OA) to surface modify vancomycin (VCM)-loaded niosomes and to evaluate their antibacterial and anti-biofilm effectiveness against methicillin-resistant Staphylococcus aureus (MRSA). The novel mPEG-OA-coated niosomes were biocompatible, hemocompatible with size, polydispersity index, and zeta potential of 169.2 +/- 1.6 nm, 0.21 +/- 0.01 and -0.82 +/- 0.22 mV, respectively. Under acidic conditions, mPEG-OA-coated niosomes exhibited a pH-responsive and sustained VCM release profile and in vitro antibacterial activity than non-coated niosomes and bare VCM. mPEG-OA-coated niosomes showed a significant reduction in biofilm formation at pH 6 compared to pH 7.4 (p = 0,0119). The in vivo efficacy of mPEG-OA-coated niosomes in the BALB/c mice skin infection model showed a 9.9-fold reduction in MRSA load compared to bare VCM. Histomorphologically, the mPEG-OA-coated niosomes group displayed the lowest bacterial load, tissue swelling, and inflammation. The results of this study demonstrate the potential of novel pH-responsive mPEG-OA-derived polymer coating to enhance bacterial killing kinetics, and antibacterial and anti-biofilm efficacies over conventional antibiotic and non-functionalized nano delivery systems.