Vancomycin-loaded nanoparticles against vancomycin intermediate and methicillin resistant Staphylococcus aureus strains

Abstract

Bacterial infections represent one of the leading causes of mortality in the world. Among causative pathogens, S. aureus is prominently known as the underlying cause of many multidrug resistant infections that are often treated with the first-line choice antibiotic vancomycin (VCM). Loading antibiotics into polymeric nanoparticles (Np) displays promise as an alternative method to deliver therapy due to the greater access and accumulation of the antibiotic at the site of the infection as well as reducing toxicity, irritation and degradation. The aim of this work was to prepare, characterize and evaluate VCM-loaded nanoparticles (VNp) for use against S. aureus strains. Moreover, conjugation of Nps with holo-transferrin (h-Tf) was investigated as an approach for improving targeted drug delivery. VNp were prepared by double emulsion solvent evaporation method using PLGA and PVA or DMAB as surfactants. The particles were characterized for size distribution, Zeta Potential, morphology by transmission electron microscopy, encapsulation yield and protein conjugation efficiency. Process yield and drug loading were also investigated along with an in vitro evaluation of VNp antimicrobial effects against S. aureus strains. Results showed that Np were spontaneously formed with a mean diameter lower than 300 nm in a narrow size distribution that presented a spherical shape. The bioconjugation with h-Tf did not appear to increase the antimicrobial effect of VNp. However, non-bioconjugated Np presented a minimal inhibitory concentration lower than free VCM against a MRSA (Methicillin-resistant S. aureus) strain, and slightly higher against a 6 Author to whom any correspondence should be addressed.

Overview on bacterial resistance and nanoparticles to overcome bacterial resistance

“…Once PLGA NPs enter the host cell, NPs release AB, which combats these intracellular microbes 87,82,73 . Vancomycin-PLGA NPs were more potent against methicillin-resistant Staphylococcus aureus 92 , as shown in Table 3. NPs can release a high conc of ABs inside infected host cells while maintaining the total dose of AB administered low 82 73 .…”

Preparation and in Vitro Characterization of Vancomycin Loaded Plga Nanoparticles for the Treatment of Enterococcus Faecalis Infections

“…Nanoparticles recovered after preparation were weighed and the production yield (%) was calculated according to Equation 3 (Eq.3) [13,14].…”

“…This migration is undesirable as it reduces encapsulation efficiency. Therefore, PVA was used as a surfactant in the external phase [14,18].…”

Functional Mapping of Phenotypic Plasticity of Staphylococcus aureus Under Vancomycin Pressure

“…S. aureus is a clinically important bacterial species, which is effectively treated using the antibiotic vancomycin ( Shahin et al, 2020 ; Simon et al, 2020 ). However, with the continuous use of antibiotics, vancomycin-resistant S. aureus strains are increasingly developing that can adapt to antibiotic environments and show strong phenotypic plasticity ( Bakri et al, 2007 ).…”