DEVELOPMENT OF DRUG DELIVERY SYSTEM TO TREAT DRUG ABUSE

需要改进阿片类药物成瘾治疗的药物疗法，以维持成瘾者的长期治疗。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。目前治疗阿片类药物成瘾的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。一种这样的阿片类药物替代剂在治疗领域是类似于阿片类药物的结构。一种这样的阿片类药物替代剂是丁丙诺啡。目前，丁丙诺啡舌下给药是治疗阿片类药物成瘾的一种研究性药物疗法。然而，丁丙诺啡的缓释制剂将比目前的剂型有优势，目前的剂型需要每天给药或每周给药三次。因此，开发一种新的丁丙诺啡给药系统，使其能够在较长时间内维持治疗用的血浆浓度，被认为是一个重要的研究领域。为了在长时间内以恒定速率递送丁丙诺啡，我们建议开发可生物降解的植入系统。这些植入系统将包括i)可生物降解的微胶囊和ii)原位聚合凝胶。这些植入系统将使用几种等级的聚（乳酸-羟基乙酸酯）和聚（己内酯）来开发。第一种递送系统，缓释微胶囊，将由一种新型的可生物降解聚合物在水混溶的生物相容性溶剂中制备，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。水混溶溶剂将从感染部位扩散，水将渗透到聚合物基质中，从而形成固体植入物。丁丙诺啡被封装在聚合物基质中，在较长时间内缓慢释放。在制备之后，将对这些输送系统的物理化学特性进行评估。这些制剂将在大鼠身上进行临床前评估，包括药代动力学研究和生物相容性研究。在成功的临床前评估之后，这些新的给药系统可以在未来用于临床试验。因此，这些新型给药系统的发展将为阿片类药物成瘾治疗带来新的药物治疗方法。

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.