Nanoparticle scavengers for in vivo sequestration of overdosed drug molecules

用于体内隔离过量药物分子的纳米颗粒清除剂

• 批准号: 8524099
• 负责人: Zhiguo Zhou
• 金额: $ 12.84万
• 依托单位: LUNA INNOVATIONS, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8524099
• 关键词: Accident and Emergency department; Affinity; Antidotes; Area; Attenuated; Binding; Blood; Blood Circulation; Body Fluids; Bupivacaine; Cardiac Death; Cardiopulmonary Resuscitation; Catecholamines; Clinical; Complement; Data; Dissociation; Dose; Drug Kinetics; Drug toxicity; Effectiveness; Emergency Medicine; Emulsions; Extravasation; Fat emulsion; Goals; Government; Healthcare; Heart Arrest; Homeostasis; Human; In Vitro; Information Systems; Intoxication; Intravenous; Investigational New Drug Application; Lead; Link; Lipids; Local Anesthetics; Medical; Mycotoxins; Overdose; Particle Size; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology and Toxicology; Phase; Plasma; Poisoning; Process; Property; Public Health; Relative (related person); Reporting; Safety; Supportive care; Surface; Technology; Therapeutic; Toxic effect; Toxicant exposure; Toxin; Translations; United States National Center for Health Statistics; Whole Blood; Work; animal efficacy; base; biocompatible polymer; clinical application; clinically relevant; crosslink; improved; in vivo; innovation; interest; nanoparticle; nanoscale; particle; pre-clinical; prevent; programs; public health relevance; success; therapeutic development; tool; treatment duration

DESCRIPTION (provided by applicant): Drug toxicity due to either overdose or abusive use represents a major healthcare problem. According to the Toxic Exposure Surveillance System data pharmaceuticals are implicated in 42% of all poisoning cases with >123,000 annual cases caused by therapeutic errors. The National Center for Health Statistics report that 22,000 people died of drug overdose in the U.S. in 2005 alone, and the number is growing rapidly. General rescue therapies such as cardiopulmonary resuscitation, intravenous catecholamines to support homeostasis are used to treat drug intoxications in emergency room. These supportive therapies work to some extent; but there is a clearly unmet need for alternative emergency medicine that can effectively and rapidly lower the toxic concentrations of overdosed drugs. In particular, accidental overdose of bupivacaine, a local anesthetic has been reported to cause many cases of cardiac arrest and death. Intralipid is the only therapeutic scavenger with demonstrated clinical success in attenuating toxicities induced by overdosed lipophilic drugs. However improvements are needed to enhance the sequestration efficiency, reduce the dosing volume, and shorten the treatment period. Luna proposes to develop core-shell therapeutic nanoparticles that are capable of extracting lipophilic molecules from body fluids to its lipophili core, and thus overdosed drug is sequestered and its effective concentration is lowered. We hypothesized that the significantly enhanced surface area to volume ratio of Luna's nanoparticles relative to Intralipid will dramatically improve the sequestration efficiency, so tha drug toxicities can be ameliorated more effectively and rapidly. Luna's nanoparticle scavenger has the potential for a successful clinical translation as an antidote to overdosed drugs. Success of such a therapeutic product would be a valuable addition to the existing clinical armamentarium in emergency room.

描述（由申请人提供）：由于过量或滥用导致的药物毒性是一个主要的医疗保健问题。根据有毒物质接触监测系统的数据，42%的中毒病例与药物有关，每年有超过123，000例病例是由治疗错误引起的。国家卫生统计中心报告说，仅在2005年，美国就有22,000人死于药物过量，而且这个数字还在迅速增长。一般的抢救治疗，如心肺复苏，静脉注射儿茶酚胺，以支持体内平衡，用于治疗药物中毒在急诊室。这些支持疗法在一定程度上起作用;但对替代急诊医学的需求显然没有得到满足，这种替代急诊医学可以有效和快速地降低过量药物的毒性浓度。特别是，意外过量的布比卡因，一种局部麻醉剂已被报道导致许多心脏骤停和死亡的病例。Intraperoid是唯一的治疗性清除剂，在减轻过量亲脂性药物诱导的毒性方面取得了临床成功。然而，需要改进以提高封存效率，减少投加体积，并缩短处理周期。Luna提出开发核-壳治疗性纳米颗粒，其能够从体液中提取亲脂性分子到其亲脂性核心，从而隔离过量的药物并降低其有效浓度。我们假设，Luna纳米颗粒相对于Intraperoid的显著增加的表面积与体积比将显著提高螯合效率，从而可以更有效和更快速地改善药物毒性。Luna的纳米颗粒清除剂具有成功的临床转化潜力，可作为过量药物的解毒剂。这种治疗产品的成功将是对急诊室现有临床设备的有价值的补充。