The development and characterization of a vancomycin nanostructured lipid carrier and evaluation of their antimicrobial properties on Staphylococcus aureus

Abstract

Vancomycin is a glycopeptide antibioticc which acts upon the cell wall of Gram-positive bacteria, causing
cell death by cell wall damage and compounding cell membrane leakage. Nanostructured lipid carriers
(NLCs) are second-generation lipidic drug delivery vehicles made from solid and liquid lipids and
stabilised with surfactants and co-surfactants. NLCs provide better clinical outcomes by increasing cell
permeation and tissue absorption and allow drugs to bypass biological barriers. Blank and vancomycin
loaded NLCs were formulated by hot homogenisation and probe sonication and optimised for
hydrodynamic size (PS), polydispersity index (PDI), zeta potential. Entrapment efficiency (%EE) was
investigated by HPLC, and drug-lipid interactions were investigated by differential scanning calorimetry
(DSC) and Fourier transform infrared spectroscopy (FTIR). This project achieved an optimised
vancomycin NLC formulation with HDS of 153.5nm ± 22.5 a PDI of 0.162 ± 0.058 and a zeta potential
of -47mV ± 3.3, and drug percentage entrapment efficiency (%EE) of 84.04% ± 3.41. DSC and FTIR did
show some potential for drug-lipid interaction due to the presence of a C=C bond and an increase in
melting point for drug encapsulated NLCs compared against blank NLCs. Bacterial testing was
conducted on S. aureus ATCC 29213 a vancomycin sensitive strain of Staphylococcus aureus.
Antimicrobial susceptibility testing highlighted that vancomycin encapsulated in NLCs showed similar
inhibitory effect as compared to free vancomycin on S. aureus culture, however, the inhibitory effect
of vancomycin was prolonged from two to four hours showing potential for a local and consistent
prolonged release at target sites, potentially alleviating rapid elimination. This project demonstrates
the potential for vancomycin embedded NLCs to effectively treat S. aureus infections showing the
possibility of maintaining the drug levels within therapeutic window for a longer period of time.