Crosslinked Nanosponges for the Topical Treatment of Wound Biofilms

用于局部治疗伤口生物膜的交联纳米海绵

• 批准号: 10189492
• 负责人: Robin Patel
• 金额: $ 38.77万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-24 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10189492
• 关键词: Anti-Bacterial Agents; Antibiotic Therapy; Antibiotics; Antimicrobial Resistance; Bacteria; Bacterial Antibiotic Resistance; Bacterial Infections; Bypass; Cells; Coculture Techniques; Development; Disease; Dose; Emulsions; Engineering; Evaluation; Excision; Exhibits; Fibroblasts; Formulation; Generations; Goals; Immune response; In Vitro; Infection; Inflammation; Laboratories; Mammalian Cell; Methods; Microbial Biofilms; Microcapsules drug delivery system; Modeling; Multi-Drug Resistance; Mus; Nature; Oils; Operative Surgical Procedures; Pathogenicity; Phytochemical; Polymers; Property; Pseudomonas aeruginosa; Refractory; Research; Resistance; Resistance Process; Siderophores; Solubility; Staphylococcus aureus; Structure; System; Testing; Therapeutic; Tissues; Topical application; Toxic effect; Volatile Oils; Wound Infection; Wound models; antimicrobial; antimicrobial drug; aqueous; bacterial resistance; bactericide; base; biomaterial compatibility; cell growth; chronic infection; cost; crosslink; cytokine; dose information; healing; in vivo; in vivo evaluation; inhibitor/antagonist; interest; methicillin resistant Staphylococcus aureus; microbicide; nanomaterials; nanomedicine; non-healing wounds; pre-clinical; prevent; quorum sensing; self assembly; systemic inflammatory response; therapeutic evaluation; wound biofilm; wound healing; wound treatment

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.

项目概要/摘要 用于局部治疗伤口生物膜的交联纳米海绵 拟议研究的目标是创造针对多重耐药性的治疗方法 生物膜感染。这些感染非常难以治疗：生物膜的难治性 感染使他们对标准抗生素具有高度耐药性，这种情况因 抗生素耐药细菌的发展。 在我们的研究中，我们将协同整合 Rotello 的纳米医学能力 帕特尔的生物膜专业知识。在初步研究中，Rotello 开发出了交联 纳米海绵吸收了精油抗菌剂，可以渗透并杀死生物膜 对宿主细胞影响最小的细菌。帕特尔创建了有效的伤口生物膜模型 允许有效评估治疗方法。 在我们提出的研究中，我们将开发新的纳米海绵疗法并对其进行测试 体外对抗生物膜，与哺乳动物细胞共培养，最后在体内。 目标 1：Rotello 将制造和表征聚合物纳米海绵并优化其活性 针对多重耐药生物膜，包括金黄色葡萄球菌 (MRSA) 生物膜模型。这些 纳米海绵将在共培养模型中针对哺乳动物细胞进行测试，目的是 最大限度地提高抗菌功效并最大限度地降低哺乳动物细胞毒性。 目标 2：Rotello 将筛选治疗药物，包括抗生素、群体感应抑制剂和 铁载体创建第二代组合抗菌剂。 目标 3：帕特尔将对优化的第一代进行给药和临床前小鼠研究 和 2 种制剂，测定伤口愈合活性。罗泰洛将筛选 炎。