Autonomous Treatment of Opioid Abuse

阿片类药物滥用的自主治疗

• 批准号: 7712500
• 负责人: Roger J Narayan
• 金额: $ 14.56万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7712500
• 关键词: Agonist; Animals; Award; Behavior; Biocompatible; Biological; Biosensor; Blood; Blood specimen; Brain; Buprenorphine; Calibration; Chemicals; Chronic; Chronic Disease; Clinical; Clinical Research; Country; Data; Dependence; Dependency; Development; Devices; Drug Delivery Systems; Drug Formulations; Drug abuse; Environment; Exhibits; Exploratory/Developmental Grant; Fingerprint; Fracture; Frequencies; HIV Seropositivity; Hepatitis; Heroin; Hybrids; Individual; Intercellular Fluid; Intramuscular; Intramuscular Injections; Joints; Laboratories; Life; Maintenance; Malignant Neoplasms; Mechanics; Medical Device; Methanol; Modality; Molecular; Monitor; Mus; Opiate Addiction; Opioid; Ormocer; Outcome; Outpatients; Pain management; Patients; Phase; Property; Public Health; Pump; Quality of life; Research; Resistance; Risk-Taking; Safety; Series; Shapes; Social Functioning; Structure; Techniques; Technology; Time; United States; Variant; Withdrawal; Withdrawal Symptom; Work; addiction; base; compliance behavior; criminal behavior; improved; in vivo; medical appointment; opioid abuse; painful neuropathy; physical conditioning; polymerization; programs; psychologic; public health relevance; research study; skills; two-photon

DESCRIPTION (provided by applicant): Opioid abuse is a common problem in the United States. It is estimated that 2.4 million people in this country use heroin at some time in their lives. Addiction to heroin has several long-term consequences, including molecular changes in the brain, hepatitis-risk taking behavior, HIV-risk taking behavior, and criminal behavior. Buprenorphine is a partial opioid agonist that has been commercially available since 1978 in sublingual form for outpatient treatment of opioid dependence. A transdermal patch is preferable to intramuscular or sublingual formulations for treatment of opioid dependence because it (a) increases patient compliance, (b) minimizes diversion of the buprenorphine for illicit use, (c) reduces the frequency of medical appointments, and (d) provides buprenorphine in a controlled manner, which minimizes fluctuations in blood concentration and limits withdrawal symptoms. However, conventional buprenorphine patches suffer from peak-and-trough variations in drug delivery. We hypothesize that two photon polymerization may be used to create fracture-resistant, biocompatible microneedle structures that can be used on a daily basis over several months for autonomous treatment of opioid addiction. An exploratory program is needed to assess the structural and functional properties of microneedle-based "smart" patches created using two photon polymerization. The proposed research plan contains four overlapping phases. Phase I will involve chemical characterization of Ormocer(R) materials created using two photon polymerization. Phase II will involve biological and functional characterization of Ormocer(R) microneedles. Phase III will involve integrating microneedles with pumping devices in autonomous "smart" patch devices. Phase IV will include a series of in vivo studies in mice to examine the predictive validity of the "smart" patch. The Phase IV experiments will build upon ongoing experiments within the co-PI's laboratory, which are examining the antinociceptive effects of opioid agonists as well as the development of tolerance and dependence following chronic opioid administration. The PI and the co-PI have already started developing preliminary studies; we have found that our complementary skills and facilities have allowed this joint research effort to progress at a much faster rate than would otherwise be possible. The proof-of-concept in vivo data from this award will form the basis for comprehensive in vivo animal and clinical studies that will examine the safety and efficacy of Ormocer(R) microneedles in a clinical environment. For example, comparison of "smart" patch against conventional patch, intramuscular injection, and other treatment modalities will be performed. We anticipate that an autonomous "smart" patch device could contribute to an improved quality of life, including improved social functioning, reduced HIV-risk taking behavior, reduced criminality, improved physical health, and improved psychological status, for patients seeking treatment for drug abuse. PUBLIC HEALTH RELEVANCE: In the proposed work, we will integrate microneedles with pumps in "smart" patches that may be used to provide autonomous management of opioid dependency and verification of compliance in a private setting. We envision several important public health outcomes from the proposed work. The data from this award will form the basis for in vivo animal and clinical studies that will examine the safety and efficacy of microneedle- based "smart" patches in a clinical environment. "Smart" patches may be used for active monitoring and treatment of patients undergoing maintenance withdrawal therapy; "phased" induction onto buprenorphine and other opioid addiction treatment agents; and management of pain resulting from cancer or other chronic conditions (e.g., neuropathic pain). Microneedles may also be integrated with multiple biosensors to provide autonomous blood sampling, analysis, calibration, and drug delivery for individualized treatment of patients with multiple chronic conditions (e.g., HIV positive status and opioid addiction). We anticipate that an autonomous "smart" patch device could contribute to an improved quality of life, including improved social functioning, reduced HIV-risk taking behavior, reduced criminality, improved physical health, and improved psychological status, for individuals seeking drug abuse treatment.

描述（由申请人提供）：阿片类药物滥用是美国常见的问题。据估计，这个国家的240万人在生活中的某个时候使用海洛因。对海洛因的成瘾会产生多种长期后果，包括大脑的分子变化，肝炎风险采取行为，艾滋病毒风险采取行为和犯罪行为。丁丙诺啡是一种部分阿片类药物激动剂，自1978年以来以舌下形式以商业形式可用，用于门诊阿片类药物依赖性。透皮斑块比肌肉内或舌下制剂可比治疗阿片类药物依赖性的治疗，因为它（a）提高了患者的依从性，（b）最大程度地减少丁丙诺啡的转移以供非法使用，（c）降低医疗预约的频率，（c）（d）在受控的良好范围中驱动buprenorphine，以降低了浓度的浓度，并限制了浓度的浓度。但是，常规的丁丙诺啡斑块遭受了药物输送的峰值和下流差异。我们假设可以使用两种光子聚合来创建抗裂缝，生物相容性的微针结构，这些结构可在几个月内每天使用，以自主治疗阿片类药物成瘾。需要一个探索性程序来评估使用两个光子聚合创建的基于微针的“智能”贴片的结构和功能特性。拟议的研究计划包含四个重叠阶段。第一阶段将涉及使用两个光子聚合产生的Ormocer（R）材料的化学表征。第二阶段将涉及Ormocer（R）微针的生物学和功能表征。第三阶段将涉及将微针与自动“智能”补丁设备中的泵送设备集成。第四阶段将包括一系列在小鼠中的体内研究，以检查“智能”斑块的预测有效性。 IV期实验将基于Co-Pi实验室中正在进行的实验，该实验正在研究阿片类药物激动剂的抗伤害感受作用，以及慢性阿片类药物给药后的耐受性和依赖性的发展。 PI和COPI已经开始开发初步研究。我们发现，我们的互补技能和设施使这项共同的研究工作能够以比以前可能更快的速度进步。该奖项的体内数据证明将构成综合体内动物和临床研究的基础，该研究将检查临床环境中Ormocer（R）微针的安全性和功效。例如，将进行“智能”斑块与常规贴片，肌肉注射和其他治疗方式的比较。我们预计，一种自主的“智能”补丁装置可能会改善生活质量，包括改善社交功能，减少艾滋病毒风险采取行为，犯罪降低，身体健康的改善和改善的心理状况，以寻求治疗药物滥用治疗的患者。公共卫生相关性：在拟议的工作中，我们将将微针与“智能”补丁中的泵整合在一起，这些泵可用于在私人环境中提供对阿片类药物依赖性和合规性验证的自主管理。我们设想了拟议工作的几个重要公共卫生结果。该奖项的数据将构成体内动物和临床研究的基础，该研究将研究基于微针的“智能”斑块在临床环境中的安全性和功效。 “智能”补丁可用于主动监测和治疗接受维持戒断疗法的患者；对丁丙诺啡和其他阿片类成瘾治疗剂的“分阶段”诱导；以及由癌症或其他慢性疾病（例如神经性疼痛）引起的疼痛的治疗。微孔系也可以与多个生物传感器集成，以提供自主抽样，分析，校准和药物递送，以对具有多种慢性疾病的患者进行个性化治疗（例如HIV阳性状态和阿片类药物成瘾）。我们预计，一种自主的“智能”补丁设备可以改善生活质量，包括改善社会功能，减少艾滋病毒风险行为，犯罪降低，身体健康的改善和改善心理状况，以寻求滥用药物治疗的人。