Self-assembled oleylamine grafted hyaluronic acid polymersomes for delivery of vancomycin against methicillin resistant Staphylococcus aureus (MRSA).

MRSA infections are a major global healthcare problem associated with high morbidity and mortality. The application of novel materials in antibiotic delivery has efficiently contributed to the treatment of MRSA infections. The aim of the study was to develop novel hyaluronic acid-oleylamine (HA-OLA) conjugates with 25-50% degrees of conjugation, for application as a nano-drug carrier with inherent antibacterial activity. The biosafety of synthesized novel HA-OLA conjugates was confirmed by in vitro cytotoxicity assay. Drug carrying ability of HA-OLA conjugates was confirmed by 26.1-43.12% of vancomycin (VCM) encapsulation in self-assembled polymersomes. These polymersomes were dispersed in nano-sized range (196.1-360.9 nm) with a negative zeta potential. Vancomycin loaded polymersomes were found to have spherical and bilayered morphology. The VCM loaded polymersomes displayed sustained drug release for 72 h. In vitro studies showed moderate antibacterial activity for HA-OLA conjugates against both S. aureus and MRSA with minimum inhibitory concentration (MIC) of 500 μg/mL. The VCM loaded HA-OLA polymersomes displayed four-fold lower MIC (1.9 μg/mL) than free VCM (7.8 μg/mL) against MRSA. Furthermore, synergism was observed for VCM and HA-OLA against MRSA. Flow cytometry showed 1.8-fold higher MRSA cell death in the population for VCM loaded polymersomes relative to free drug, at concentration of 1.95 μg/mL. Bacterial cell morphology showed that the drug loaded polymersomes had stronger impact on MRSA membrane, compared to free VCM. These findings suggest that, HA-OLA conjugates are promising nano-carriers to function as antibiotic delivery vehicles for the treatment of bacterial/MRSA infections.