SR Drug Delivery for the Treatment of Drug Abuse

用于治疗药物滥用的 SR 药物输送

• 批准号: 6555563
• 负责人: TARUN K MANDAL
• 金额: $ 6.81万
• 依托单位: XAVIER UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6555563
• 关键词: buprenorphine; drug abuse therapy; drug delivery systems; drug vehicle; high performance liquid chromatography; histochemistry /cytochemistry; laboratory rabbit; laboratory rat; method development; microcapsule; pharmacokinetics; scanning electron microscopy; slow release drug

DESCRIPTION (provided by applicant): The long-term objective of this project is to develop a novel treatment for drug abuse. Buprenorphine is a highly lipophilic partial mu-opiate agonist, which is being tested for opiate maintenance program. In order to provide long-term constant buprenorphine delivery, it is desirable to develop a sustained release formulation, which could be implanted subcutaneously. In order to deliver buprenorphine at a constant rate over a prolonged period, we propose to develop sustained release microcapsules. We hypothesize that subcutaneous administration of buprenorphine microcapsules will deliver long-term therapeutic plasma concentrations of buprenorphine. The specific aims of this proposal are to: (1) develop sustained release microcapsules of buprenorphine, (2) evaluate in vitro drug release characteristics of the microcapsules, (3) evaluate in vivo performance of the microcapsules, and (4) evaluate the long-term stability of the microcapsules. Buprenorphine microcapsules will be prepared using poly(lactide-co-glycolide) by a novel microencapsulation technique. This unique microencapsulation technique has been developed in the PI's laboratory, where the active ingredients are incorporated within a hydrogel followed by microencapsulation within a synthetic biodegradable polymer. Preliminary experiments just completed in our laboratory revealed that the use of a crosslinked hydrogel, before the microencapsulation, could significantly increase the drug loading. It also revealed that the drug was present within the hydrogel in the dissolved state. As a result, incorporation of the hydrogel significantly reduced the burst effect and overall dissoluation of the drug. The buprenorphine microcapsules will be tested in rabbits for in vivo release and biocompatibility. The microcapsules will also be tested in a rat model for agonist effect and heroin dose effect. Following the successful preclinical evaluations in rabbits and rats, this novel delivery system can be used, in the future, for evaluation in monkeys followed by human clinical trials.

描述（由申请人提供）：该项目的长期目标是开发一种新的药物滥用治疗方法。丁丙诺啡是一种高度亲脂性的部分多阿片激动剂，目前正在进行阿片维持计划的试验。为了提供长期稳定的丁丙诺啡给药，需要开发一种可皮下植入的缓释制剂。为了使丁丙诺啡在长时间内以恒定速率释放，我们建议开发缓释微胶囊。我们假设皮下注射丁丙诺啡微胶囊将提供长期治疗的丁丙诺啡血浆浓度。本课题的具体目的是：(1)研制丁丙诺啡缓释微胶囊；(2)评价微胶囊的体外释药特性；(3)评价微胶囊的体内性能；(4)评价微胶囊的长期稳定性。丁丙诺啡微胶囊是一种新型的微胶囊化技术。这种独特的微胶囊技术是在PI的实验室开发的，其中活性成分被掺入水凝胶中，然后被微胶囊化在合成的可生物降解聚合物中。我们实验室刚刚完成的初步实验表明，在微胶囊化之前使用交联水凝胶可以显著增加药物的负载。它还揭示了药物以溶解状态存在于水凝胶中。结果，水凝胶的掺入显著降低了药物的破裂效应和总溶出度。丁丙诺啡微胶囊将在家兔体内进行释放和生物相容性测试。微胶囊还将在大鼠模型中进行激动剂效应和海洛因剂量效应的测试。在兔子和大鼠的临床前评估成功之后，这种新型的递送系统可以在未来用于猴子的评估，然后进行人体临床试验。