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(申请人提供)：过量或滥用引起的药物毒性是一个主要的医疗保健问题。根据毒性暴露监测系统的数据，在每年12.3万起由治疗失误导致的中毒案例中，有42%与药物有关。国家卫生统计中心报告称，仅在2005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。急诊室一般采用心肺复苏、静注儿茶酚胺等维持体内平衡的抢救方法来救治药物中毒。这些支持性疗法在一定程度上起到了作用；但对于能够有效、迅速地降低过量药物的毒性浓度的替代紧急医学，显然还有一种尚未得到满足的需求。特别是，据报道，当地麻醉剂布比卡因意外过量导致许多心脏骤停和死亡。Intralipid是唯一一种临床证明在减轻过量亲脂性药物引起的毒性方面取得成功的治疗性清除剂。但需要改进，以提高隔离效率，减少投药量，缩短治疗周期。露娜建议开发核壳治疗纳米粒，这种纳米粒能够从体液中提取亲脂分子到其亲脂核心，从而隔离过量的药物，降低其有效浓度。我们推测，与Intralipid相比，露娜纳米粒的比表面积与体积比显著提高，从而显著提高了包封率，从而可以更有效、更迅速地改善药物毒性。露娜的纳米颗粒清除剂有可能成功地转化为临床上过量药物的解毒剂。这种治疗产品的成功将是对现有急诊室临床医疗设施的宝贵补充。