Abstract
The present study is aimed at the employment of novel fatty acid derived lipids for the preparation of pH-responsive nanostructured lipid carriers (NLCs) for vancomycin (VCM) intravenous delivery against resistant and sensitive Staphylococcus aureus bacteria. Two branched lipids [stearic acid derived solid lipid and oleic acid derived liquid lipid] were synthesized, characterized and used to fabricate NLCs by hot homogenization technique. Particle size, polydispersity index, zeta potential and encapsulation efficiency were 225.2 ± 9.1 nm, 0.258 ± 0.02, −9.2 ± 2.7 mV and 88.7 ± 13.12%, respectively. An understanding of drug encapsulation efficiencies and formation of the NLCs were supported by in silico studies. In vitro antibacterial activity revealed that VCM loaded-NLCs had higher activity against methicillin-susceptible and resistant Staphylococcus aureus than the bare VCM. Cell viability study showed that NLCs had 2.5-fold better killing percentage than the bare drug at similar concentrations. Furthermore, the in vivo efficacy of VCM loaded-NLCs was assessed in a mouse model of MRSA skin infection. MRSA CFU load of the skin treated with NLCs was 37-fold lower than bare VCM (p < 0.05). This novel pH-responsive NLCs may, therefore, show potential for efficient and enhanced antibiotic delivery.
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