Novel Intracellular Antibiotic Delivery System Against Staphylococcus Aureus : Cloxacillin-Loaded Poly( D , L -Lactide-Co-Glycolide) Acid Nanoparticles

Abstract

Aim: First, to compare in vitro minimum inhibitory concentrations (MIC) of free cloxacillin and cloxacillin-containing nanoparticles (NP) against methicillin-susceptible (MSSA) and resistant Staphylococcus aureus (MRSA) and second, to assess NP antimicrobial activity against intracellular S. aureus. Methods: Poly(d,l-lactide-co-glycolide) acid (PLGA)-NP were loaded with cloxacillin and physico-chemically characterized. MICs were determined for reference strains Newman-(MSSA) and USA300-(MRSA). Murine alveolar macrophages were infected, and bacterial intracellular survival was assessed after incubating with free-cloxacillin or PLGA-cloxacillin-NP. Results & conclusion: For both isolates, MICs for antibiotic-loaded-NP were lower than those obtained with free cloxacillin, indicating that the drug encapsulation improves antimicrobial activity. A sustained antibiotic release was demonstrated when using the PLGA-cloxacillin-NP. When considering the lowest concentrations, the use of drug-loaded NP enabled a higher reduction of intracellular bacterial load.

Antibiofilm Synergistic Activity of Streptomycin in Combination with Thymol-Loaded Poly (Lactic-co-glycolic Acid) Nanoparticles against Klebsiella pneumoniae Isolates

“…For instance, PLGA nanoparticles loaded with curcumin showed greater antibacterial activity on different bacterial strains than free curcumin [ 26 ]. Additionally, Lacoma et al reported significant antimicrobial activity of cloxacillin-loaded PLGA nanoparticles compared to free cloxacillin against Staphylococcus aureus [ 27 ]. Cardamom oil-loaded chitosan nanoparticles were found to exhibit excellent antimicrobial potential against extended-spectrum lactamase-producing Escherichia coli and methicillin-resistant Staphylococcus aureus [ 28 ].…”

“…In addition, the phenolic hydroxy group of thymol enhanced its hydrophilic property, leading to inhibition of bacterial growth and even killing them [6]. Improved [27]. Cardamom oil-loaded chitosan nanoparticles were found to exhibit excellent antimicrobial potential against extended-spectrum lactamase-producing Escherichia coli and methicillin-resistant Staphylococcus aureus [28].…”

Biocompatible Polycationic Silver Nanocluster‐Impregnated PLGA Nanocomposites with Potent Antimicrobial Activity

“…The MIC and MBC values of pAgNCs@PLGA were found to be lower compared to pAgNCs alone, which indicates that pAgNCs have greater antibacterial potency when loaded in PLGA. The reason may be due to better delivery of pAgNCs in its site of action and the improvement of antibacterial activity due to encapsulation in PLGA [39,50] . This finding could also be attributed to the degradation of lactic acid which has a weak lipophilic nature and its passage through the cell membrane, releasing protons, acidifying the cytoplasm, causing homeostatic imbalance and contributing to the antibacterial effect of pAgNCs [51] .…”

“…The reason may be due to better delivery of pAgNCs in its site of action and the improvement of antibacterial activity due to encapsulation in PLGA. [39,50] This finding could also be attributed to the degradation of lactic acid which has a weak lipophilic nature and its passage through the cell membrane, releasing protons, acidifying the cytoplasm, causing homeostatic imbalance and contributing to the antibacterial effect of pAgNCs. [51] SEM images of the bacteria exposed to pAgNCs and composites are shown in Figure 5(A-F).…”

Improving Antibacterial Activity of a HtrA Protease Inhibitor JO146 against Helicobacter pylori: A Novel Approach Using Microfluidics-Engineered PLGA Nanoparticles

“…Encapsulation of antimicrobial drugs into NPs can improve muco-adhesion and penetration of cell membranes, as well as intracellular delivery of antibiotics to combat various bacteria (e.g. Staphylococcus aureus [18][19][20], Escherichia coli [21], Mycobacterium abscessus [19], Klebsiella pneumonia [22], Chlamydia trachomatis [23] and Mycobacterium tuberculosis [24,25]), including those that are classified as extracellular pathogens but also show intracellular residence in host cells. Despite its promise as an alternative avenue for combating bacteria, understanding the interaction between NP and cells and management of nanomaterial toxicity often associated with inorganic nanomaterials remain as an important consideration for nanomaterial-based therapeutics [26].…”