Development of a novel combination of anti-septic taurolidine encased in a digestible nanoparticle system for use as topical treatment at burn sites

摘要

ABSTRACT Burn injury care has improved in the past decades, but complications still occur and lead to prolonged hospital stays and potentially to death. The risk of infection rises as a result of burns since the skin layers, which function as a barrier and prevent pathogens from accessing the susceptible body tissues, are no longer intact. Importantly, infections involving gram-negative or gram-positive pathogens are still the most common cause of mortality in burn injury patients. Although topical treatments exist, there is a need for an antiseptic that can effectively penetrate to the site of infection and that can be used for treatment of pathogens found in medical facilities. To address this need, CorMedix proposes to develop a combination of taurolidine encased in digestible nanosystems as topical treatment at burn sites. This proposed gel formulation will be administered to the skin surface and will penetrate through to the epidermal/dermal junction at which it will be digested by local tissue enzymes, releasing taurolidine, a taurine amino acid derivative with broad antibacterial action against gram-positive and gram-negative bacteria, mycobacteria and some clinically relevant fungi. CorMedix's proposed product will combine the proven antiseptic capabilities of taurolidine with effective delivery to the site of infection, allowing prevention and treatment of infections including those caused by pathogens that have already been found to be resistant to currently used antiseptics. CorMedix will develop this proposed product and demonstrate successful penetration of taurolidine to the site of infection through two Specific Aims. In Specific Aim #1, a gel formulation with taurolidine containing nanoparticles will be developed by (1) Selection of a buffer that facilitates taurolidine stability during the nanosystem manufacturing process; (2) Selection of material for nanosystem surface (3); Testing of nanosystem susceptibility to subcutaneous tissue enzymes; and (4) Selection of gel matrix for suspension of nanoparticles. In Specific Aim #2, the developed formulation will be tested in vitro using a Franz cells model.