Novel Cationic Amphiphiles

About

Summary: The emergence of antibiotic resistance drives the need for antibacterial agents that maintain efficacy against wildtype and multi-drug resistant bacteria. Naturally occuring antimicrobial peptides (AMPs) associate with and disrupt the bacterial membrane causing cell death, a mechansim that is difficult for bacteria to develop drug resistance to. The potential for low drug resistance has made AMPs a promising broad-range antibacterial therapy. Rutgers scientists have developed cationic amphiphiles that chemically mimic AMPs.  Both microduiltion and kinetic kill assays revealed that these synthetic amphiphiles not only inhibit bacterial growth but also kill bacteria. Further chemical modification of charge and length of the hydrocarbon tail allows for tunability. Two types of cationic amphiphiles were developed: bola-like cationic amphiphiles (BLCAs) and gemini-like cationic amphiphiles (GLCAs), which showed activity against various gram-positive and gram-negative bacteria in low concentration ranges. These amphiphiles were shown to associate with model membranes using Langmuir monolayer assays and isothermal calorimetry. The ability of cationic amphiphiles to weaken the bacterial membrane allows for synergism with conventional antibiotics. Furthermore, cationic amphiphiles can be incorporated into different formulations (e.g., liposomes) for drug delivery, household, and personal care applications.     Market Application: •  Novel therapeutics with µM activity against gram + and – bacteria •  Potent against bacterial pathogens associated with foodborne illnesses and drug resistance •  Additives in detergents and personal care products •  Potential for liposomal or nanoparticle-based drug delivery  •  Active surface coatings (e.g., paint additives)   Advantages: •  Can be engineered for selective or broad-range antibacterial therapy  •  Inhibitory activity comparable to conventional antibiotics •  Highly versatile chemistry •  Current synthesis route takes 4 steps and is carried out on a 1 gram lab scale, with potential for low-cost scaled-up manufacturing •  Biocompatible and biodegradable, which can result in less stress on the environment when used in detergents and personal care products