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 在过去的几十年里，烧伤护理有所改善，但并发症仍然存在，导致住院时间延长和住院时间延长 可能会导致死亡。感染的风险由于烧伤而增加，因为皮肤层起着屏障的作用， 防止病原体进入易受感染的身体组织，不再完好无损。重要的是，感染涉及 革兰氏阴性或革兰氏阳性病原体仍然是烧伤患者死亡的最常见原因。虽然 局部治疗已经存在，需要一种能够有效渗透到感染部位的防腐剂，并且可以 用于治疗医疗设施中发现的病原体。为了解决这一需求，CorMedex建议开发一种 在可消化的纳米系统中联合应用牛磺酸核苷作为烧伤部位的局部治疗。这是一种建议的凝胶 配方会涂在皮肤表面，并会渗透到表皮/真皮交界处 它将被局部组织酶消化，释放出牛磺酸，一种具有广泛抗菌作用的氨基酸衍生物 对革兰氏阳性和革兰氏阴性细菌、分枝杆菌和一些临床相关真菌的作用。CorMedex‘s 建议的产品将结合牛磺酸利定已被证明的防腐能力和有效地输送到 感染，允许预防和治疗感染，包括那些由已经被 被发现对目前使用的防腐剂具有抗药性。 CorMedex将开发这种拟议的产品，并展示牛磺酸利定成功地渗透到感染部位 通过两个具体目标。在具体目标#1中，含有牛磺酸利定纳米粒的凝胶配方将是 通过(1)选择在纳米系统制造过程中促进牛磺酸核苷稳定性的缓冲液； (2)纳米系统表面材料的选择(3)；纳米系统对皮下组织酶的敏感性测试； (4)纳米颗粒悬浮液凝胶基质的选择。在具体目标#2中，制定的配方将是 使用Franz细胞模型进行体外测试。

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.