Crosslinked Nanosponges for the Topical Treatment of Wound Biofilms

项目摘要/摘要 用于伤口生物膜局部治疗的交联型纳米微球 这项拟议的研究的目标是创造对抗多重耐药的治疗方法。 生物被膜感染。这些感染很难治疗：生物被膜的难治性 感染使他们对标准抗生素产生高度抗药性，这种情况因 抗生素耐药细菌的发展。 在我们的研究中，我们将协同地将Rotello的纳米医学能力与 帕特尔的生物膜专业知识。在初步研究中，罗特洛研制出了交联型 吸附了精油抗菌剂的纳米棒可以穿透并杀死生物被膜 对宿主细胞影响最小的细菌。Patel创造了有效的伤口生物膜模型 允许对治疗学进行有效评估。 在我们提出的研究中，我们将开发新的纳米疗法并对其进行测试。 在体外，在与哺乳动物细胞的共培养中，最后在体内抗生物膜。 目标1：Rotello将制备和表征聚合物纳米微球，并优化其活性 对抗多重耐药生物被膜，包括金黄色葡萄球菌(MRSA)生物被膜模型。这些 纳米粒子将在共培养模型中与哺乳动物细胞进行测试，目标是 最大限度地提高抗菌效果，最大限度地降低哺乳动物细胞毒性。 目标2：罗特罗将筛选治疗药物，包括抗生素、群体感应抑制剂和 铁载体创造第二代组合抗菌剂。 目标3：Patel将对优化的第一代进行剂量和临床前小鼠研究 和2个配方，确定伤口愈合活性。罗特洛将筛选出 发炎。

Project Summary/Abstract Crosslinked Nanosponges for the Topical Treatment of Wound Biofilms The goal of the proposed research is the creation of therapeutics against multidrug-resistant biofilm infections. These infections are very difficult to treat: The refractory nature of biofilm infections make them highly resistant to standard antibiotics, a situation exacerbated by the development of antibiotic-resistant bacteria. In our research we will synergistically integrate the nanomedicine capabilities of Rotello with biofilm expertise of Patel. In preliminary research Rotello has developed crosslinked nanosponges imbibed with essential oil antimicrobials that penetrate and kill biofilm-based bacteria with minimal effect on host cells. Patel has created effective wound biofilm models that allow efficient assessment of therapeutics. In our proposed research we will develop new nanosponge therapeutics and test them against biofilms in vitro, in co-culture with mammalian cells, and finally in vivo. Aim 1: Rotello will fabricate and characterize polymeric nanosponges and optimize their activity against multi-drug resistant biofilms including S. aureus (MRSA) biofilm models. These nanosponges will be tested against mammalian cells in co-culture models, with the goal of maximizing antibacterial efficacy and minimizing mammalian cell toxicity. Aim 2: Rotello will screen therapeutics including antibiotics, quorum sensing inhibitors, and siderophores to create Generation 2 combination antibacterial agents. Aim 3: Patel will perform dosing and pre-clinical mouse studies of the optimized Generation 1 and 2 formulations, determining wound healing activity. Rotello will screen for inflammation.