![](data:image/png;base64,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)
Cationic amphiphiles greatly inhibits the biofilm formation of the pathogenic bacteria in BV. Cationic Amphiphile Concentration (μM)
Invention Summary:
Bacterial vaginosis (BV) is a common polymicrobial infection in women of reproductive age, affecting 10-30% of women in developed nations. BV can lead to serious complications such as abortion, premature birth and pelvic inflammatory disease. Current antibiotic treatment regimens often fail to fully eradicate the pathogenic biofilm and may lead to recurrance due to antibiotic resistence. Antimicrobial peptides (AMPs) hold great potential in treating BV as they can effectively disrupt the bacterial membrane causing cell death, a mechansim that is difficult for bacteria to develop drug resistance to. However, intrinsic drawbacks associated with AMPs, such as low metabolic stability (i.e., susceptibility to proteolysis), high manufacturing cost and formulation difficulties have precluded their translation into clinical arena.
Rutgers scientists have developed two series of cationic amphiphiles (CAms) that chemically mimic AMPs. Compared to AMPs, these ether- and ester-linked CAms showed higher stability and solubility, high biodegradability, and good efficacy against various gram-positive and gram-negative bacteria. In an in vitro study, the CAms were shown to effectively inhibit BV-associated pathogens but not the healthy vaginal bacteria lactobacilli. Using the biofilm crystal violet staining assay, the CAms were shown to strongly inhibit the biofilm formation of the BV pathogenic bacteria with µM activities and are much tolerated by the healthy bacteria lactobacilli.
In addition, CAms also display synergistic effects when used in combination with metronidazole, a commonly used antibiotic to treat BV. Furthermore, scanning electron microscopy (SEM) revealed considerable morphological and ultrastructural changes in treated biofilms, confirming the membrane-targeting effects of CAms. These results suggest CAms are a promising new generation of antimicrobials for treating bacterial vaginosis.
Market Applications:
- Novel therapeutics to treat BV.
- Novel combination therapeutics with metronidazole to treat BV.
- Additives in personal care products to prevent or treat BV.
Advantages:
- Capable of eradicating pathogenic biofilms
- Strong antimicrobial effects with µM activity
- Unlikely to result in resistance due to its membrane-disruption mechanism
- Well-tolerated by the healthy vaginal bacteria lactobacilli
- Highly versatile chemistry with potential for improvement
- Biocompatible, biodegradable and eco-friendly
Intellectual Property & Development Status:
Patent issued. Available for licensing and/or research collaboration.