Synthesis of an oleic acid based pH-responsive lipid and its application in nanodelivery of vancomycin.

Abstract

Antibiotic resistance is a health challenge that can make the most useful antibiotics ineffective against bacterial infections. Stimuli-responsive nano-drug delivery systems can optimize antibiotic delivery to infection sites. Identifying novel lipids for pH responsive delivery to acidic conditions of infection sites will enhance the performance of nano-drug delivery systems. The aim of this investigation was to synthesize and characterize a novel pH-responsive lipid for vancomycin delivery to acidic conditions of infection sites. A pH-responsive solid lipid, N-(2-morpholinoethyl) oleamide (NMEO), was synthesized and used to prepare vancomycin (VCM)-loaded solid lipid nanoparticles (VCM_NMEO SLNs). The particle size (PS), polydispersity index (PDI), zeta potential (ZP) and entrapment efficiency (EE) of the formulation were 302.8 ± 0.12 nm, 0.23 ± 0.03, -6.27 ± 0.017 mV and 81.18 ± 0.57 % respectively. The study findings also revealed that drug release and antibacterial activity were significantly greater at a pH 6.0 than at pH 7.4. Moreover, the reduction of MRSA load was 4.14 times greater (p <0.05) in the skin of VCM_NMEO SLNs treated mice than that were bare VCM treated. Thus, this study confirmed that NMEO can successfully be used to formulate pH-responsive SLNs, and have the potential to enhance treatment of bacterial infections.