Abstract
The aim of this study was to synthesize a novel biocompatible pH-responsive oleic acid-based dendritic lipid amphiphile (OLA-SPDA) which self-assembled into stable micelles (OLA-SPDA -micelles) with a relatively low critical micelle concentration (CMC) of 5.6 × 10−6 M. The formulated micelles had particle size, polydispersity index (PDI) and zeta potential (ZP) of 84.16 ± 0.184 nm, 0.199 ± 0.011 and −42.6 ± 1.98 mV, respectively, at pH 7.4. The vancomycin (VCM) encapsulation efficiency was 78.80 ± 3.26%. The micelles demonstrated pH-responsiveness with an increase in particle size to 141.1 ± 0.0707 nm and a much faster release profile at pH 6.0, as compared to pH 7.4. The minimum inhibitory concentration (MIC) of VCM-OLA-SPDA-micelle against methicillin-resistant staphylococcus aureus (MRSA) was 8-fold lower compared to bare VCM, and the formulation had a 4-fold lower MIC at pH 6.0 when compared to the formulation's MIC at pH 7.4. MRSA viability assay showed the micelles had a percentage killing of 93.39% when compared bare-VCM (58.21%) at the same MIC (0.98 μg/mL). In vivo mice (BALB/c) skin infection models showed an 8-fold reduction in MRSA burden after treatment with VCM-OLA-SPDA-micelles when compared with bare VCM. The above results suggest that pH-responsive VCM-OLA-SPDA-micelles has the potential to be an effective carrier to enhance therapeutic outcomes against infections characterised by low pH.
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