Niosomes modified with a novel pH-responsive coating (mPEG-OA) enhance the antibacterial and anti-biofilm activity of vancomycin against methicillin-resistant Staphylococcus aureus
Nawras Osman, Calvin A. Omolo, Mohammed A. Gafar, Nikita Devnarain, Sanjeev Rambharose, Usri H. Ibrahim, Victoria Oluwaseun Fasiku, Thirumala Govender
Abstract
Abstract 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.