Maltoheptaose based nanotherapeutics for multidrug resistant bacterial infection

基于麦芽七糖的纳米疗法治疗多重耐药细菌感染

• 批准号: 8647713
• 负责人: MINGDI YAN
• 金额: $ 20.5万
• 依托单位: UNIVERSITY OF MASSACHUSETTS LOWELL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8647713
• 关键词: Adopted; Affect; Animals; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotics; Antimicrobial Resistance; Bacteria; Bacterial Infections; Biodistribution; Carbon; Cell Membrane Permeability; Cells; Clinical; Development; Disinfectants; Dose; Drug Delivery Systems; Drug resistance; Economics; Effectiveness; Encapsulated; Equus caballus; Escherichia coli; Evaluation; Exhibits; Health; Health Care Costs; Healthcare Systems; Human; In Vitro; Infection; Liposomes; Mammalian Cell; Marketing; Medical center; Metabolic; Micelles; Morbidity - disease rate; Multi-Drug Resistance; Mycobacterium tuberculosis; Nutrient; Pharmaceutical Preparations; Pseudomonas aeruginosa; Public Health; Reporting; Resistance; Risk; Source; Streptomycin; System; Technology; Testing; Therapeutic; Therapeutic Agents; Time; Toxic effect; Translations; Treatment Efficacy; Vancomycin resistant enterococcus; antimicrobial; antimicrobial drug; base; cost; drug resistant bacteria; effective therapy; improved; in vivo; innovation; killings; maltodextrin; maltoheptaose; methicillin resistant Staphylococcus aureus; microorganism; mortality; mouse model; nanoparticle; nanotherapeutic; pathogen; prevent; public health relevance; research study; uptake

DESCRIPTION (provided by applicant): Antimicrobial resistance has a major public health risk where drugs are no longer effective against microorganisms. Once powerful antimicrobial agents have now become virtually useless, and the situation is spreading rapidly over the globe. The objective of this proposal is to develop a new strategy for targeting multidrug-resistant bacteria, composed of therapeutics-encapsulated nanoparticles with maltoheptaose (G7) as the targeting agent. The key hypothesis is that G7 will greatly facilitate the uptake of nanoparticles by bacterial cells whereas the multivalent nanoparticles will deliver high local doses of therapeutics into bacterial cells to achieve significantly enhanced antibiotic potency. G7, a maltodextrin that is the largest carbon source for metabolic activity, will be used as the targetin agent as we have shown that it drastically increased the uptake of nanoparticles by bacterial cells whereas it had minimal impact on mammalian cells. In addition, we hypothesize that G7-tagged nanoparticles will improve considerably the efficacy of antibiotics in treating multidrug-resistant bacterial infection. During the two-year project period, we will synthesize and study the antimicrobial activities of antibiotics-encapsulated G7-liposomes and G7-micelles against multidrug-resistant Pseudomonas aeruginosa in vitro. We will also evaluate the in vivo efficacy of the new nanotherapeutics using a mice model. The completion of these studies will demonstrate that G7-based nanotherapeutics will improve appreciably the therapeutic efficacy of antibiotics and revert the antimicrobial resistance of P. aeruginosa. The proposal is innovative because it represents the first study to use a nutrient as the targeting strategy for drug delivery The project is significant because results from these studies can be readily applied to other systems, thus a universal platform can be envisioned for enhancing the delivery of a diverse class of therapeutic agents to treat multidrug-resistant bacterial infections.

描述(由申请人提供)：抗菌素耐药性是一种重大的公共健康风险，药物对微生物不再有效。曾经强大的抗菌剂现在几乎毫无用处，而且这种情况正在迅速蔓延到全球。这项提议的目的是开发一种新的靶向多药耐药细菌的策略，由以麦芽七糖(G7)为靶向剂的治疗药物包裹的纳米颗粒组成。关键假设是，G7将极大地促进细菌细胞对纳米粒子的摄取，而多价纳米粒子将向细菌细胞输送高局部剂量的治疗药物，以实现显着增强的抗生素效力。G7是代谢活动的最大碳源，它将被用作目标蛋白，因为我们已经证明，它显著增加了细菌细胞对纳米颗粒的摄取，而对哺乳动物细胞的影响很小。此外，我们假设G7标记的纳米颗粒将显著提高抗生素在治疗多重耐药细菌感染方面的疗效。在两年的项目期内，我们将综合和研究 抗生素包裹的G7脂质体和G7胶束对多重耐药铜绿假单胞菌的体外抗菌活性。我们还将使用小鼠模型评估新的纳米疗法的体内疗效。这些研究的完成将证明，基于G7的纳米疗法将显著提高抗生素的治疗效果，并逆转铜绿假单胞菌的抗药性。这项提议是创新的。 由于这是第一个使用营养素作为药物输送的靶向策略的研究，该项目具有重要意义，因为这些研究的结果可以很容易地应用于其他系统，因此可以设想一个通用平台，以加强不同类别的治疗剂的输送，以治疗耐多药细菌感染。