Combination Therapeutic for Chronic Opioid Use Disorder Relapse

慢性阿片类药物使用障碍复发的联合治疗

• 批准号: 10706844
• 负责人: TREVOR P. CASTOR
• 金额: $ 33.57万
• 依托单位: APHIOS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10706844
• 关键词: Acids; Address; Adherence; Adult; Adverse effects; Aftercare; Alcohol consumption; Alcohol dependence; Alcohols; Animal Model; Animals; Arousal; Behavior; Binding; Biological Availability; Buprenorphine; Cannabidiol; Cannabinoids; Cannabis sativa plant; Chronic; Clinical; Clinical Trials; Conduct Clinical Trials; Cue-induced relapse; Cues; Cyclic GMP; Dependence; Development; Dose; Drug Combinations; Economic Burden; Economics; Encapsulated; Epidemic; FDA approved; Female; Formulation; Frequencies; Friends; Funding; Future; Health Care Costs; Hemp; Heroin; Human; Hydrophobicity; In Vitro; Individual; Industry; Insulin; Intramuscular; Legal patent; Licensing; Marijuana; Medical; Methadone; Morphine; Motivation; Mus; Naltrexone; Nanosphere; Narcotics; Opiate Addiction; Opioid; Opioid Antagonist; Opioid abuser; Opioid agonist; Patients; Personal Satisfaction; Persons; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Substance; Phase; Polymers; Prevention; Proteins; Public Health; Regulatory Pathway; Relapse; Reporting; Research; Risk; Safety; Sister; Stomach; Stress; Technology; Therapeutic; Treatment Efficacy; United States; Wistar Rats; Withdrawal; Withdrawal Symptom; addiction; age group; biodegradable polymer; bryostatin; clinical development; craving; delta opioid receptor; experience; improved; in vivo; in vivo evaluation; lofexidine; male; manufacture; manufacturing scale-up; mu opioid receptors; nano; nanoencapsulated; nanoformulation; nanoparticle; nanopolymer; non-compliance; non-opioid analgesic; novel; opioid epidemic; opioid overdose; opioid use; opioid use disorder; opioid withdrawal; pain symptom; pandemic disease; programs; relapse prevention; research and development; response; scale up; side effect; social; success; treatment adherence; treatment duration; uptake

PROJECT SUMMARY Few therapeutics are available for individuals trying to recover from opioid use disorder. Buprenorphine and methadone, opioid receptor agonists, are approved by the FDA to treat Opioid Use Disorder (OUD) but long- term efficacy and treatment adherence are sub-optimal. Extended-release naltrexone (Vivitrol®, Alkermes), a full µ-opioid receptor antagonist, was approved by the FDA in 2010 for the prevention of relapse to opioid dependence but initiation and adherence to treatment are low. There is an urgent need for improved treatments for chronic relapsing opioid use disorder that has serious public health consequences. For the treatment of chronic relapsing OUD, we propose to develop an extended-release combination of low- dose naltrexone and cannabidiol (CBD) by nanoencapsulating them in biodegradable polymer nanospheres using an environmental-friendly proprietary SuperFluids™ technology. CBD has been shown to inhibit cue- induced heroin seeking in animals, and subsequent human clinical trial studies have revealed its potential utility and safety. Animal studies have shown that low-dose naltrexone, when combined with CBD, is better than either of the two in isolation to improve motivation and alcohol consumption in mice. This combination is promising, considering that naltrexone primarily targets the μ opioid receptor, and CBD binds the μ and δ opioid receptors. Lowering the dose of naltrexone will be impactful since it will reduce the side effects of Vivitrol®, and improve safety and compliance. This novel formulation will significantly enhance the bioavailability and pharmacodynamics of the two therapeutics, reduce dose frequency, and improve addiction treatment adherence. In Phase I, we will develop nanoformulations of CBD and low-dose naltrexone/CBD in biodegradable polymer nanospheres, and assess the intramuscular administration of the nanoparticles to reduce OUD relapse compared to Vivitrol® in an animal model of OUD relapse. In Phase II, we will conduct a more extensive R&D program that includes scale-up of cGMP manufacturing, GLP in vitro and in vivo product characterization, and establish the regulatory pathway for clinical development. In Phase III, with strategic corporate partners and/or investors, we will conduct clinical trials of CBD/naltrexone PLGA nanoparticles in patients suffering from chronic relapsing opioid use disorder.

项目摘要 试图从阿片类药物使用障碍中恢复的个人很少有治疗。丁丙诺啡和 FDA批准了阿片类药物受体激动剂，用于治疗阿片类药物使用障碍（OUD），但长期 期限效率和治疗依从性是最佳的。扩展释放纳曲酮（Vivitrol®，Alkermes），A FDA于2010年批准了全µ-Apoid受体拮抗剂，以防止继电器与卵毒素 依赖性但主动性和对治疗的依从性很低。迫切需要改进治疗 对于具有严重公共卫生后果的慢性复发型阿片类药物使用障碍。 为了治疗慢性复发Oud，我们建议开发低释放的组合 通过在可生物降解的聚合物纳米球中对纳米封闭的剂量纳曲酮和大麻二醇（CBD） 使用环境友好的专有Superfluids™技术。 CBD已被证明抑制提示 诱导动物寻求海洛因的诱导海洛因，随后的人类临床试验揭示了其潜在的效用 和安全。动物研究表明，低剂量纳曲酮与CBD结合时，比任何一个要好 在孤立的两者中，以改善小鼠的动力和饮酒。这种组合是有希望的， 考虑到纳曲酮主要靶向μOiOID受体，并且CBD结合μ和δoioid受体。 降低纳曲酮的剂量将产生影响，因为它将减少Vivitrol®的副作用，并改善 安全和合规性。这个新颖的公式将显着增强生物利用度和 两种治疗剂的药物动力学，降低剂量频率并改善成瘾治疗依从性。 在第一阶段，我们将开发可生物降解聚合物中CBD和低剂量纳曲酮/CBD的纳米制剂 纳米球，并评估纳米颗粒的肌内给药以减少OUD退休 与Oud浮雕动物模型中的Vivitrol®相比。在第二阶段，我们将进行更广泛的研发 程序包括扩大CGMP制造，体外和体内产品表征的GLP以及 建立临床发展的调节途径。在第三阶段，与战略公司合作伙伴和/或 投资者，我们将对患有慢性的患者进行CBD/Naltrexone PLGA纳米颗粒的临床试验 复发阿片类药物使用障碍。