Loading of polymyxin B onto anionic mesoporous silica nanoparticles retains antibacterial activity and enhances...

Area of Science:

• Materials Science
• Nanotechnology
• Pharmaceutical Sciences

Background:

• Polymyxin B is a critical last-resort antibiotic for multidrug-resistant Gram-negative bacteria.
• Toxicity limits the clinical application of polymyxin B.
• Mesoporous silica nanoparticles (MSNs) are explored for drug delivery applications.

Purpose of the Study:

• To investigate the adsorption of polymyxin B onto bare and surface-modified MSNs.
• To enhance the therapeutic properties of polymyxin B by formulating it with MSNs.
• To evaluate the antibacterial activity and biocompatibility of polymyxin B-loaded MSNs.

Main Methods:

• Synthesis and characterization of mesoporous silica nanoparticles (MSNs).
• Adsorption studies of polymyxin B onto MSNs, investigating parameters like pH, buffer type, and nanoparticle surface charge (ζ-potential).
• Kinetic analysis of adsorption and drug release profiles (Power law and Hill models).
• Evaluation of antibacterial efficacy against Gram-negative bacteria and assessment of cytotoxicity, including reactive oxygen species (ROS) generation.

Main Results:

• MSNs demonstrated significant adsorption capacity for polymyxin B, with optimal conditions identified (bare MSNs, Tris buffer, pH 9).
• The highest adsorption capacity reached approximately 401 mg/g.
• Polymyxin B-loaded MSNs exhibited sustained release and enhanced antibacterial activity compared to free polymyxin B.
• Loading polymyxin B onto MSNs reduced its cytotoxicity by decreasing ROS generation.

Conclusions:

• MSNs are effective adsorbents for polymyxin B, improving its therapeutic index.
• Formulating polymyxin B with MSNs offers a viable approach to mitigate its toxicity while preserving antimicrobial efficacy.
• This MSN-based drug delivery system holds promise for treating infections caused by antibiotic-resistant Gram-negative bacteria.