Engineered Polymer Nanoemulsions for Treatment of Wound Biofilm Infections

项目摘要 用于治疗伤口生物被膜感染的工程聚合物纳米乳液 这项拟议研究的目标是创造针对多重耐药生物被膜感染的新疗法。 这些感染很难治疗。生物被膜感染的耐受性使它们对 标准抗生素，这种情况因获得性抗菌素耐药性而加剧。 在我们的研究中，我们将Rotello的纳米医学能力与创伤生物膜的专业知识相结合 Patel开发使用交联型聚合物网络稳定的交联型纳米乳液(XNEs) 精油的纳米液滴。这些XNE在对宿主细胞影响最小的情况下杀死基于生物膜的细菌，并且可以 通过在XnE的油成分中加入抗菌剂来根除生物膜。XNE有好的一面 使用Patel开发的体内伤口生物膜模型的有效性(杀死生物膜中99%的≥细菌)。一致 然而，对于其他抗菌纳米材料，在体内的杀灭效果不如体外。 在我们提出的研究中，Rotello将开发新的嵌段共聚物来生成嵌段共聚物XnE(B-XnE) 治疗学。然后将B-XNEs加入水凝胶伤口敷料中，以提供受控释放 治疗伤口感染的B-XNE。伤口敷料中的B-XNEs和B-XNEs将在体外和体内进行测试 使用逼真且具有挑战性的伤口生物膜模型。 目标1：Rotello将合成嵌段共聚物，并使用这些嵌段共聚物来参数改变B-XNE的尺寸和电荷。 然后，这些B-XNEs将用于携带抗生素，提供与精油的协同活性。B-XNE将 使用发光的耐甲氧西林金黄色葡萄球菌(MRSA)生物膜筛选活性，以及 然后，罗特罗和帕特尔对其他细菌进行了测试。利用哺乳动物细胞的共培养模型 将被用于降低选择最大限度地提高抗菌活性和最大限度地减少哺乳动物细胞毒性的药物。 目标2：Rotello将在水凝胶中加入B-XNEs，以提供抗菌伤口敷料。B-XNE和 将共同设计水凝胶，以提供B-XNEs的受控释放。这些B-XnE将使用以下方法进行筛选 发光MRSA以确定有前景的B-XnE-水凝胶组合，并进一步由Rotello进行如Aim 1中的测试 还有帕特尔。 目的3：Rotello和Patel将使用小鼠伤口生物膜模型来测试B-XNEs和B-XnE创面敷料。 这些研究将结合使用Rotello的发光MRSA的参数试点实验和全面的临床前试验 帕特尔对MRSA和鲍曼不动杆菌创面生物膜的评价。在这些模型中的功效将是 通过减少细菌数量、促进伤口愈合和减少脓肿作为结果进行量化。

Project Summary Engineered Polymer Nanoemulsions for Treatment of Wound Biofilm Infections The goal of the proposed research to create new therapeutics targeting multidrug-resistant biofilm infections. These infections are difficult to treat. The refractory nature of biofilm infections make them non-responsive to standard antibiotics, a situation exacerbated by acquired antibacterial resistance. In our research, we have integrated the nanomedicine capabilities of Rotello with wound biofilm expertise of Patel to develop crosslinked nanoemulsions (XNEs) that use a crosslinked polymer network to stabilize nanodroplets of essential oils. These XNEs kill biofilm-based bacteria with minimal effects on host cells and can eradicate biofilms through incorporation of antimicrobials into the oil component of the XNE. XNEs have good efficacy (killing ≥99% of bacteria in biofilms) using the in vivo wound biofilm model developed by Patel. Consistent with other antimicrobial nanomaterials, however, killing is less effective in vivo than in vitro. In our proposed research, Rotello will develop new block copolymers to generate block copolymer XNE (B-XNE) therapeutics. The B-XNEs will then be incorporated into hydrogel wound dressings to provide controlled release of B-XNEs to treat wound infections. B-XNEs and B-XNEs in wound dressings will be tested in vitro and in vivo using realistic and challenging wound biofilm models. Aim 1: Rotello will synthesize block copolymers and use these to parametrically vary size and charge of B-XNEs. These B-XNEs will then be used to carry antibiotics, providing synergistic activity with essential oils. B-XNEs will be screened for activity using luminescent methicillin-resistant Staphylococcus aureus (MRSA) biofilms, and then tested against other bacterial species by Rotello and Patel. Co-culture models employing mammalian cells will be used to downselect agents that maximize antibacterial activity and minimize mammalian cell toxicity. Aim 2: Rotello will incorporate B-XNEs into hydrogels to provide antimicrobial wound dressings. B-XNEs and hydrogels will be co-engineered to provide controlled release of B-XNEs. These B-XNE will be screened using luminescent MRSA to identify promising B-XNE-hydrogel combinations, and further tested as in Aim 1 by Rotello and Patel. Aim 3: Rotello and Patel will use murine wound biofilm models to test B-XNEs and B-XNE wound dressings. These studies will combine parametric pilot experiments using luminescent MRSA by Rotello with full pre-clinical evaluation by Patel with MRSA and Acinetobacter baumannii wound biofilms. Efficacy in these models will be quantified by decreased bacterial counts, enhanced wound healing, and diminished purulence as outcomes.