Engineered Polymer Nanoemulsions for Treatment of Wound Biofilm Infections

用于治疗伤口生物膜感染的工程聚合物纳米乳液

• 批准号: 10655643
• 负责人: Robin Patel
• 金额: $ 37.8万
• 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 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10655643
• 关键词: Acinetobacter baumannii; Adhesions; Affect; Anti-Bacterial Agents; Antibiotic Therapy; Antibiotics; Architecture; Bacteria; Bacterial Counts; Bacterial Drug Resistance; Bacterial Infections; Biocompatible Materials; Biological Assay; Cells; Charge; Clinical Treatment; Coculture Techniques; Coupled; Disease; Dose; Drug resistance; Elderly; Emulsions; Engineering; Environment; Excision; Foundations; Gel; Goals; Hydrogels; Hydrophobicity; Immune response; In Vitro; Infection; Infiltration; Mammalian Cell; Methods; Microbial Biofilms; Modeling; Multi-Drug Resistance; Mus; Nature; Oils; Operative Surgical Procedures; Outcome; Pathogenicity; Penetration; Persons; Phytochemical; Polymers; Population; Refractory; Research; Resistance; Serial Passage; Sterile coverings; Surface Properties; System; Testing; Therapeutic; Tissues; Toxic effect; Video Microscopy; Volatile Oils; Wound Infection; Wound models; antimicrobial; antimicrobial drug; bactericide; biomaterial compatibility; chronic infection; chronic wound; controlled release; copolymer; cost; crosslink; design; di-block copolymer; experimental study; extracellular; healing; in vitro activity; in vitro testing; in vivo; in vivo evaluation; luminescence; methicillin resistant Staphylococcus aureus; nanoDroplet; nanoemulsion; nanomaterials; nanomedicine; nanoparticle; nanopolymer; new therapeutic target; particle; preclinical evaluation; scaffold; self assembly; uptake; wound; wound biofilm; wound dressing; wound environment; wound healing; wound treatment

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.

项目概要 用于治疗伤口生物膜感染的工程聚合物纳米乳液 拟议研究的目标是创造针对多重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 标准抗生素，这种情况因获得性抗菌药物耐药性而加剧。 在我们的研究中，我们将 Rotello 的纳米医学能力与伤口生物膜专业知识相结合 Patel 开发使用交联聚合物网络来稳定的交联纳米乳液 (XNE) 精油的纳米液滴。这些 XNE 杀死基于生物膜的细菌，对宿主细胞的影响最小，并且可以 通过在 XNE 的油成分中加入抗菌剂来消除生物膜。 XNE 具有良好的 使用 Patel 开发的体内伤口生物膜模型进行功效（杀死生物膜中≥99% 的细菌）。持续的 然而，对于其他抗菌纳米材料，体内杀灭效果不如体外有效。 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） 疗法。然后，B-XNE 将被纳入水凝胶伤口敷料中，以提供控制释放 B-XNE 治疗伤口感染。 B-XNE 和伤口敷料中的 B-XNE 将进行体外和体内测试 使用现实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，并使用它们来参数化地改变 B-XNE 的尺寸和电荷。 然后，这些 B-XNE 将用于携带抗生素，与精油提供协同活性。 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 Rotello 和 Patel 对其他细菌进行了测试。采用哺乳动物细胞的共培养模型 将用于筛选能够最大化抗菌活性并最小化哺乳动物细胞毒性的药物。 目标 2：Rotello 将把 B-XNE 融入水凝胶中，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 的控制释放。这些 B-XNE 将使用 发光 MRSA 来识别有前景的 B-XNE-水凝胶组合，并按照 Rotello 的目标 1 进行进一步测试 和帕特尔。 目标 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。 这些研究将使用 Rotello 的发光 MRSA 进行参数试验与完整的临床前研究相结合。 Patel 对 MRSA 和鲍曼不动杆菌伤口生物膜进行了评估。这些模型的功效将是 通过减少细菌数量、增强伤口愈合和减少化脓来量化结果。

项目成果

Biodegradable Poly(lactic acid) Stabilized Nanoemulsions for the Treatment of Multidrug-Resistant Bacterial Biofilms.

• DOI: 10.1021/acsami.1c11265
• 发表时间: 2021-09-01
• 期刊: ACS applied materials & interfaces
• 影响因子: 9.5
• 作者: Oz Y;Nabawy A;Fedeli S;Gupta A;Huang R;Sanyal A;Rotello VM
• 通讯作者: Rotello VM

Antimicrobial polymer-siRNA polyplexes as a dual-mode platform for the treatment of wound biofilm infections.

抗菌聚合物-siRNA 复合物作为治疗伤口生物膜感染的双模式平台。

• DOI: 10.1039/d3mh01108a
• 发表时间: 2023
• 期刊: Materials horizons
• 影响因子: 13.3
• 作者: Jeon,Taewon;Makabenta,JessaMarieV;Park,Jungmi;Nabawy,Ahmed;Cicek,YagizAnil;Mirza,SarahS;Welton,Janelle;Hassan,MuhammadAamir;Huang,Rui;Mager,Jesse;Rotello,VincentM
• 通讯作者: Rotello,VincentM

Activity of Biodegradable Polymeric Nanosponges against Dual-Species Bacterial Biofilms.

• DOI: 10.1021/acsbiomaterials.0c01433
• 发表时间: 2021-05-10
• 期刊: ACS biomaterials science & engineering
• 影响因子: 5.8
• 作者: Nabawy A;Makabenta JM;Li CH;Park J;Chattopadhyay AN;Schmidt-Malan S;Gupta A;Patel R;Rotello VM
• 通讯作者: Rotello VM

Polymeric Nanoparticles Active against Dual-Species Bacterial Biofilms.

• DOI: 10.3390/molecules26164958
• 发表时间: 2021-08-16
• 期刊: Molecules (Basel, Switzerland)
• 作者: Makabenta JMV;Park J;Li CH;Chattopadhyay AN;Nabawy A;Landis RF;Gupta A;Schmidt-Malan S;Patel R;Rotello VM
• 通讯作者: Rotello VM

Nanomaterial-based therapeutics for antibiotic-resistant bacterial infections.

• DOI: 10.1038/s41579-020-0420-1
• 发表时间: 2021-01
• 期刊: Nature reviews. Microbiology
• 作者: Makabenta JMV;Nabawy A;Li CH;Schmidt-Malan S;Patel R;Rotello VM
• 通讯作者: Rotello VM