Abstract
Infectious diseases remain a major burden in today’s world, causing high mortality rates and significant economic losses, with >9 million deaths per year predicted by 2030. Invasion of host cells by intracellular bacteria poses treatment challenges due to the poor permeation of antimicrobials into the infected cells. To overcome these limitations, mesoporous silica nanoparticles (MSNP) loaded with the antibiotic rifampicin were investigated as a nanocarrier system for the treatment of intracellular bacterial infection with specific interest in the influence of particle size on treatment efficiency. An intracellular infection model was established using small colony variants (SCV) of S. aureus in macrophages to systemically evaluate the efficacy of rifampicin-loaded MSNP against the pathogen as compared to a rifampicin solution. As hypothesized, the superior uptake of MSNP by macrophages resulted in an enhanced treatment efficacy of the encapsulated rifampicin as compared to free antibiotic. This study provides a potential platform to improve the performance of currently available antibiotics against intracellular infections.
Highlights
Since the discovery of penicillin in 1928, antibiotics have saved millions of lives worldwide [1].once penicillin became commercially available and was more widely used, clinically resistant bacteria rapidly evolved in the 1950s [1,2]
It is important to note that the concentration of antibiotics at the target locations is required to be above the minimum inhibitory concentration (MIC) or minimum bactericidal concentration (MBC), to avoid the re-development of antibacterial resistance by exposure
Hiroshima mesoporous material (HMM)-type mesoporous silica nanoparticles with particle sizes of 40 nm (MSNP-40) and 100 nm (MSNP-100) were successfully synthesized
Summary
Since the discovery of penicillin in 1928, antibiotics have saved millions of lives worldwide [1].once penicillin became commercially available and was more widely used, clinically resistant bacteria rapidly evolved in the 1950s [1,2]. Some bacterial species have found a niche to survive the process and live inside the host cells, shielded from standard antibacterial drugs. This poses a significant challenge for treatment of intracellular infections since many antibiotics have low permeability into the cells, poor intracellular retention or poor stability in the acidic environment inside the host cells [2,5,6,7]. It is important to note that the concentration of antibiotics at the target locations is required to be above the minimum inhibitory concentration (MIC) or minimum bactericidal concentration (MBC), to avoid the re-development of antibacterial resistance by exposure
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