Abstract
Background: Streptococcus pneumoniae remains a major cause of community-acquired pneumonia, meningitis, and other diseases, contributing significantly to high morbidity and mortality worldwide. Although it responds to antibiotics, their use is becoming limited due to the rise in antibiotic resistance, which necessitates the development of new therapeutics. Nanotechnology is used to counteract antimicrobial resistance. In this regard, polymeric nanoparticles (NPs) made of natural, biodegradable, biocompatible, and cationic polymers such as Chitosan (CNPs) exhibit wide-spectrum antimicrobial activity. Therefore, this study aimed to prepare CNPs, characterize their physiochemical characteristics: particle size (PZ), polydispersity index (PDI), and zeta potential (ZP), and investigate their antimicrobial activity against Streptococcus pneumoniae TIGR4 (virulent serotype 4) and its capsular mutant (∆cps). Methods: CNPs were prepared at 1, 2.5, and 5 mg/mL concentrations using the ion gelation method. Then, PZ, PDI, and ZP were characterized using a Zetasizer. Transmission electron microscopy (TEM) was used to visualize the CNP’s morphology. Broth and agar dilution methods were used to assess their antimicrobial activity. Cytotoxicity of prepared NPs on A549 cells and their effect on pneumococcal hemolysis were also investigated. Results: Spherical CNPs were produced with PZ ranging from 133.3 nm ± 0.57 to 423 nm ± 12.93 PDI < 0.35, and ZP from 19 ± 0.115 to 27 ± 0.819. The prepared CNPs exhibited antibacterial activity against TIGR4 and its capsule mutant with a minimum inhibitory concentration (MIC90) of 0.5 to 2.5 mg/mL in a non-acidic environment. The hemolysis assay results revealed that CNPs reduced bacterial hemolysis in a concentration-dependent manner. Their mammalian cytotoxicity results indicated that CNPs formed from low concentrations of Chitosan (Cs) were cytocompatible. Conclusion: Nanochitosan particles showed anti-pneumococcal activity regardless of the presence of capsules. They resulted in a concentration-dependent reduction in bacterial hemolysis and were cytocompatible at a lower concentration of Cs. These findings highlight the potential of CNPs in the treatment of pneumococcal diseases.
Highlights
Streptococcus pneumoniae is a gram-positive bacterium and a major human pathogen
Dulbecco’s modified Eagle’s medium (DMEM), fetal bovine serum (FBS), and antibiotic-antimycotic solution were obtained from Gibco (Grand Island, NY, USA)
CNPs were successfully obtained adopting the ion gelation method as reported by former studies [16,19], which is based on crosslinking between cationic Cs and anionic TPP
Summary
Streptococcus pneumoniae (the pneumococcus) is a gram-positive bacterium and a major human pathogen. The use of nanotechnology, polymeric nanoparticles (PNPs), has emerged in recent years as an alternative tool to develop antimicrobial therapeutics [4,5] In this regard, NPs made from natural polymers such as Chitosan (Cs) have received much attention lately. Streptococcus pneumoniae remains a major cause of community-acquired pneumonia, meningitis, and other diseases, contributing significantly to high morbidity and mortality worldwide It responds to antibiotics, their use is becoming limited due to the rise in antibiotic resistance, which necessitates the development of new therapeutics. Nanotechnology is used to counteract antimicrobial resistance In this regard, polymeric nanoparticles (NPs) made of natural, biodegradable, biocompatible, and cationic polymers such as Chitosan (CNPs) exhibit wide-spectrum antimicrobial activity. These findings highlight the potential of CNPs in the treatment of pneumococcal diseases
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