Novel Fatty Acid-Based pH-Responsive Nanostructured Lipid Carriers For Enhancing Antibacterial Delivery.

Bacterial infections have been recognized as a major cause of deaths globally due to the limitations of current antibiotic conventional dosage forms. The introduction of nano delivery systems, primarily smart pH-responsive nano antibiotic delivery systems, can potentiate targeted antibiotic release; therefore, combat conventional dosage forms limitations and reduce resistance development. Formulation of pH-responsive nanostructured lipid carrier (NLCs) for targeted delivery of vancomycin (VCM) using synthesized novel fatty acid-based lipids that and undergo surface charge reversal in acidic medium. Two branched lipids [ stearic acid derived solid lipid and oleic acid-derived liquid lipid] were synthesized and characterized using FTIR, 1H and 13C NMR. The NLCs were prepared using hot homogenization technique and characterized in terms of size, polydispersity index (PDI), zeta potential (ZP) (Dynamic Light Scattering), surface morphology (TEM), encapsulation efficiency (EE) (HPLC), in vitro drug release (Dialysis bag), cell viability study (flow cytometry), in vitro (broth dilution) and in vivo (mice skin infection model) antibacterial activity. VCM-NLCs were spherically shaped with size, PDI and ZP of 225.9 ± 9.1 nm, 0.258 ± 0.02 and -9.2 ± 2.7 mV respectively. EE (%) was 88.7±13.12. In vitro drug release studies revealed that VCM release was faster at pH 6 compared to pH 7.4. Cell viability study showed that NLCs had 2.5-fold better killing percentage than the bare drug at similar concentrations. Invitro antibacterial activity against methicillin-susceptible and resistant Staphylococcus aureus proved that at pH 6 NLCs activity was four times and two times better against SA and MRSA, respectively. Interestingly, at pH 6 it was 8 times better than bare VCM against both bacterial strains. In vivo study revealed that MRSA CFU load in mice skin treated with VCM-NLCs was 4-fold lower than bare VCM (p 0.0108). This novel pH responsive NLCs can improve bacterial infection treatment by protecting the antibiotics during systemic circulation, improve the targeted antibiotic release and enhance antibiotic localization at the acidic infection sites. Therefore, pH responsive NLCs show potential for efficient antibiotic delivery and serve as a promising nanocarrier for the delivery of poorly soluble antibiotics to enhance the treatment of infections. [ABSTRACT FROM AUTHOR]