Engineered Polymer Nanoemulsions for Treatment of Wound Biofilm Infections

项目摘要 用于治疗伤口生物膜感染的工程聚合物纳米乳液 该研究的目标是创造针对多药耐药生物膜感染的新疗法。 这些感染很难治疗。生物膜感染的难治性使它们对抗生素无反应。 标准抗生素，获得性抗菌药物耐药性加剧了这种情况。 在我们的研究中，我们将Rotello的纳米医学能力与 Patel开发交联纳米乳液（XNE），使用交联聚合物网络来稳定 nanodroplets nanodroplets of essential精油.这些XNE杀死基于生物膜的细菌，对宿主细胞的影响最小， 通过将抗微生物剂掺入XNE的油组分中来消除生物膜。XNE具有良好的 使用由Patel开发的体内伤口生物膜模型测定疗效（杀死生物膜中≥99%的细菌）。一致 然而，使用其他抗微生物纳米材料，体内杀灭效果不如体外。 在我们提出的研究中，Rotello将开发新的嵌段共聚物，以生成嵌段共聚物XNE（B-XNE） 治疗学然后将B-XNE掺入水凝胶伤口敷料中以提供控释 B-XNE来治疗伤口感染将在体外和体内对伤口敷料中的B-XNE和B-XNE进行测试 使用现实的和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，并使用这些参数改变B-XNE的大小和电荷。 然后，这些B-XNE将用于携带抗生素，提供与精油的协同活性。B-XNE将 使用发光耐甲氧西林金黄色葡萄球菌（MRSA）生物膜筛选活性，和 然后由Rotello和Patel对其他细菌物种进行测试。采用哺乳动物细胞的共培养模型 将被用来向下选择最大化抗菌活性和最小化哺乳动物细胞毒性的试剂。 目标2：Rotello将B-XNE掺入水凝胶中，以提供抗菌伤口敷料。B-XNE和 水凝胶将被共同设计以提供B-XNE的受控释放。这些B-XNE将使用 发光MRSA，以鉴定有前景的B-XNE-水凝胶组合，并由Rotello如Aim 1中进一步测试 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-XNE和B-XNE伤口敷料。 这些研究将结合联合收割机参数试点实验，使用发光MRSA的Rotello与完整的临床前 由Patel用MRSA和鲍曼不动杆菌伤口生物膜进行评价。这些模型中的有效性将 通过减少的细菌计数、增强的伤口愈合和减少的化脓作为结果来量化。

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.