Ceragenins, also known as CSAs, are synthetic, non-peptide small molecule mimetics of endogenous host defense or antimicrobial peptides. Ceragenins have broad-spectrum activity mimicking those of endogenous host defense peptides, including antimicrobial, anti-inflammatory and other therapeutic activities.
Ceragenins are synthetic small molecules that can be manufactured in large scale and, unlike endogenous antimicrobial peptides, are not subject to proteolytic degradation. Over 100 ceragenins have been synthesized to date. Ceragenins consist of a sterol backbone with amino acids and other chemical groups attached to them. These compounds have a net positive charge that is electrostatically attracted to the negatively charged cell membranes of certain bacteria, fungi and viruses.
- Ceragenins exhibit antimicrobial activity by attacking the membranes of microorganisms, as opposed to their replication mechanisms. This results in broad-spectrum efficacy and improbability that resistance will develop, similar to naturally-occurring antimicrobial peptides.
- Ceragenins have demonstrated the ability to both prevent and eradicate bacterial and fungal biofilms, which are nearly impossible to eradicate utilizing conventional antibiotics.
- Ceragenins are active against both Gram-negative and Gram-positive bacteria, including multi-drug resistant strains, and against carbapenem-resistant strains, biofilms, and fungi. Ceragenins have a high binding affinity for such membranes and are able to quickly disrupt the target membranes, leading to rapid cell death. While ceragenins have a mechanism of action similar to antimicrobial peptides, which form part of the body’s innate immune system, they avoid many of the difficulties associated with the use of antimicrobial peptides as medicines.
- Lead ceragenin compounds have exhibited potent antimicrobial properties and are rapidly bactericidal, fungicidal and virucidal against a wide array of pathogens, including multidrug resistant strains of Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (Pseudomonas). Preclinical testing of these lead compounds has displayed high potency at low doses, and the absence of toxic response at doses much higher than those expected to be clinically necessary.
- In one twelve-week study funded by the National Institutes of Health (NIH), ceragenin-containing coatings on orthopedic fracture fixation plates provided 100% protection against an implanted biofilm challenge of MRSA. All of the control animals (sheep) developed osteomyelitis compared to zero of the group treated with ceragenin-based antimicrobial coated devices. The long duration and substantial bacterial challenge withstood by the ceragenin-coated device group in this in vivo implant test indicates a high likelihood of efficacy with respect to other ceragenin-coated devices that are used for shorter duration or that are exposed to a lesser bacterial challenge.
Strong Anti-inflammatory and Immunomodulatory Activities
- The anti-inflammatory and immunomodulatory properties of ceragenins function similarly to naturally-occurring cathelicidin antimicrobial peptides, and participate in various immunomodulatory pathways.
- Ceragenins are capable of modulating key inflammatory cytokines. Further, ceragenins can induce expression of chemokines, neutralize endotoxins, stimulate angiogenesis and apoptosis, suppress neutrophil apoptosis, and accelerate wound healing and osteogenesis.
Well-Studied and Recognized
N8 Medical is developing a series of products under its CeraShield™ brand that can be deployed as a platform across the medical device market and the materials commonly used to manufacture medical devices, and that provide the flexibility and customization needed to prevent hospital acquired infections and address other medical device-related issues. Additional information is available here.