Novel telodendrimer nanoparticles have been developed to enhance the delivery and safety profile of the antibiotic Polymyxin B by improving its stability and reducing toxicity during treatment.
Background: Polymyxin B (PMB) is a powerful antibiotic used to treat infections caused by Gram-negative bacteria, but its clinical application is limited due to high toxicity, particularly nephrotoxicity, and poor stability in the bloodstream. These challenges prompted research into advanced drug delivery systems that could maintain the antibiotic's effectiveness while minimizing harmful side effects. The need for safer and more effective PMB formulations or other peptide antibiotics is especially critical for treating severe conditions such as sepsis, where controlling both bacterial infection and inflammatory response is essential.
Technology Overview: This technology employs telodendrimer nanoparticles (TD NPs) featuring polyanionic charges and hydrophobic groups that encapsulate polymyxin B or other peptide antibiotics via electrostatic and hydrophobic interactions. The encapsulation improves PMB’s stability and retention in the bloodstream, allowing for slower drug release and prolonged systemic distribution compared to free PMB. The TD NPs not only deliver PMB effectively but also directly kill Gram-negative bacteria and neutralize septic molecules such as pathogen- and damage-associated molecular patterns (PAMPs and DAMPs), which trigger harmful inflammation. Comprehensive characterization techniques validate the nanoparticle size, stability, and drug loading, while biological testing confirms maintained antibacterial potency, reduced cytotoxicity, and effective immune modulation in vitro. This multifunctional delivery system addresses critical issues of toxicity and instability, positioning it as a promising alternative to conventional PMB therapies for managing infections and sepsis-induced hyperinflammation.
https://suny.technologypublisher.com/files/sites/adobestock_860641498.jpeg Photo for reference only, not a depiction of the invention.
Advantages: • Enhanced stability and controlled release of polymyxin B or other peptide antibiotics, prolonging its therapeutic window. • Reduced cytotoxicity, minimizing side effects such as nephrotoxicity associated with free PMB. • Effective neutralization of bacterial endotoxins and inflammatory molecules, supporting immune system regulation. • Maintains strong antibacterial activity while modulating harmful immune responses related to sepsis.
Applications: • Treatment of Gram-negative bacterial infections with improved safety and efficacy. • Therapeutic management of sepsis by controlling both infection and the resulting cytokine storm. • Potential use in clinical settings requiring systemic antibiotic delivery with reduced toxicity. • Platform technology for future nanodrug formulations targeting complex infectious and inflammatory diseases.
Intellectual Property Summary: Patent application filed
Stage of Development: TRL 3
Licensing Status: This technology is available for licensing.