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）：药物过量或滥用引起的毒性是一个主要的医疗问题。根据毒物暴露监测系统的数据，42%的中毒病例与药物有关，每年有123,000例病例是由治疗错误引起的。美国国家卫生统计中心报告称，仅2005年一年，美国就有2.2万人死于药物过量，而且这个数字还在迅速增长。一般抢救治疗方法如心肺复苏、静脉注射儿茶酚胺维持体内平衡等用于急诊室药物中毒的治疗。这些支持性疗法在一定程度上起作用；但是，对于能够有效和迅速降低过量药物毒性浓度的替代急诊药物的需求显然没有得到满足。特别是，意外过量使用布比卡因（一种局部麻醉剂）已被报道造成许多心脏骤停和死亡病例。脂质内是唯一的治疗性清除剂，在减轻过量的亲脂性药物引起的毒性方面取得了临床成功。但在提高固存效率、减少给药量、缩短处理周期等方面仍需改进。Luna提议开发一种核-壳治疗性纳米粒子，能够将体液中的亲脂分子提取到其亲脂核中，从而隔离过量药物并降低其有效浓度。我们假设Luna’s纳米颗粒相对于Intralipid的表面积体积比的显著增强将显著提高固相效率，从而更有效、更快速地改善药物毒性。Luna的纳米颗粒清除剂有可能成功地在临床转化为过量药物的解毒剂。这种治疗产品的成功将是对现有急诊室临床设备的宝贵补充。