DEVELOPMENT OF DRUG DELIVERY SYSTEM TO TREAT DRUG ABUSE

开发药物输送系统来治疗药物滥用

• 批准号: 6318329
• 负责人: TARUN K MANDAL
• 金额: $ 5.71万
• 依托单位: XAVIER UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6318329
• 关键词: biotransformation; buprenorphine; drug addiction antagonist; drug design /synthesis /production; gel filtration chromatography; injection /infusion; laboratory rat; microcapsule; pharmacokinetics; polymers; scanning electron microscopy; slow release drug; surface coating

Improved pharmacotherapies for the opioid addiction treatment are needed to maintain addicts in treatment for extended periods. Development of a novel drug delivery system will also keep the addicts away from high-risk tuberculosis and HIV/AIDS transmission associated with the intravenous drug abuse. One of the current treatments for opioid addiction is to use opioid agonists and/or antagonists, which generally have chemical structures similar to those of opioid. One such opioid substitution agent on the treatment horizon is structures similar to those of opioid. One such opioid substitution agent on the treatment horizon is buprenorphine. Currently, sublingual administration of buprenorphine is an investigational pharmacotherapy for the treatment of opioid addiction. However, a sustained release preparation of buprenorphine will have an advantage over current dosage forms, which require dosing daily or three times a week. Thus, the development of a novel drug delivery system of buprenorphine capable of maintaining a therapeutically useful plasma concentration over an extended period is recognized as an important area of research. In order to delivery buprenorphine at a constant rate over a prolonged period, we proposed to develop biodegradable implant systems. These implant systems will include i) biodegradable microcapsules, and ii) in situ polymeric gel. These implant systems will be developed using several grades of poly(lactide-co-glycolide) and poly(caprolactone). The first delivery system, sustained release microcapsules, will be prepared by a novel biodegradable polymers in a water miscible biocompatible solvent, e.g., N-methyl-2- pyrrolidone, dimethyl sulfoxide, ethyl acetate, acetone, ethanol, and propylene glycol. This polymer solution containing buprenorphine will be injected into the body. The water miscible solvent will diffuse from the site of infection and water will permeate into the polymer matrix resulting in a solid implant. Buprenorphine, encapsulated into polymer matrix, will release slowly over an extended period. Following the preparation, these delivery systems will be evaluated for physicochemical characteristics. These preparations will be tested in rats for preclinical evaluations, which include pharmacokinetic studies and biological compatibility studies, Following the successful preclinical evaluations, these novel delivery systems can be used, in the future, for clinical trials. Thus, the development of these novel delivery systems will bring a new pharmacotherapy for opioid addiction treatment.

需要改进阿片类药物成瘾治疗的药物疗法，以使成瘾者长期接受治疗。开发一种新的药物输送系统也将使吸毒者远离与静脉注射药物滥用有关的高风险结核病和艾滋病毒/艾滋病传播。目前阿片类药物成瘾的治疗方法之一是使用阿片类药物激动剂和/或拮抗剂，它们通常具有与阿片类药物相似的化学结构。在治疗范围内的一种这样的阿片样物质替代剂是与阿片样物质类似的结构。在治疗范围内的一种这样的阿片样物质替代剂是丁丙诺啡。目前，丁丙诺啡舌下给药是一种用于治疗阿片类药物成瘾的研究药物疗法。然而，丁丙诺啡的持续释放制剂将具有优于当前剂型的优势，当前剂型需要每天或每周三次给药。因此，开发能够在延长的时间段内维持治疗上有用的血浆浓度的丁丙诺啡的新型药物递送系统被认为是重要的研究领域。为了在长时间内以恒定速率递送丁丙诺啡，我们提出开发可生物降解的植入系统。这些植入物系统将包括i）可生物降解的微胶囊，和ii）原位聚合物凝胶。这些植入物系统将使用几个等级的聚（丙交酯-共-乙交酯）和聚（己内酯）开发。第一种递送系统，缓释微胶囊，将通过在水混溶性生物相容性溶剂中的新型生物可降解聚合物制备，例如，N-甲基-2-吡咯烷酮、二甲亚砜、乙酸乙酯、丙酮、乙醇和丙二醇。这种含有丁丙诺啡的聚合物溶液将被注射到体内。水混溶性溶剂将从感染部位扩散，并且水将渗透到聚合物基质中，从而产生固体植入物。丁丙诺啡包封在聚合物基质中，将在较长时间内缓慢释放。制备后，将评价这些输送系统的理化特性。这些制剂将在大鼠中进行临床前评价，其中包括药代动力学研究和生物相容性研究。在成功的临床前评价之后，这些新型递送系统将来可用于临床试验。因此，这些新型给药系统的开发将为阿片类药物成瘾的治疗带来新的药物疗法。