DEVELOPMENT OF BIODEGRADABLE DRUG DELIVERY SYSTEM TO TREAT ADDICTION

申请人摘要： 目前治疗阿片成瘾的方法之一是使用阿片 拮抗剂，其化学结构通常与 鸦片类药物。治疗鸦片成瘾需要使用这些药物 在很长一段时间内吸毒。几年来，美沙酮， 纳曲酮和丁丙诺啡已被用于阿片类药物的治疗 独立的个体。这些药物的缓释制剂 将比目前需要剂量的剂型更有优势 每天或一周三次。因此，开发一种可生物降解的 阿片类拮抗剂的递送系统，能够维持 治疗有用的血浆浓度被认为是一种重要的 研究领域。可生物降解的缓释微胶囊 聚合物已被开发用于多种治疗剂。然而， 目前由单一药物组成的微胶囊技术 分散在聚合物基质中有几个缺点。这其中的一个 缺点就是所谓的“突发效应”。这是由于 释放被困在表面的药物 在制造过程中的聚合物。一旦这一快速释放 停止后，微囊能够以相当快的速度释放药物 恒定的速率，通常是可取的。这种“爆发效应”可能是 通过利用两个相间的相分离现象来最小化 不相容的聚合物溶解在相互的溶剂中。第二种聚合物 将在药物/聚合物基质上提供保护性涂层。这 一步法将提供稳定的涂层，即使是非常小的涂层 纳米粒子，并将有助于通过减少“爆发”而平滑 这些双层微囊将用 以下可生物降解的聚合物组合：聚乳酸和 聚苯乙烯；聚乳酸和聚乳酸-乙交酯共聚物(50：50)； 聚乳酸和聚乙交酯；聚苯乙烯和聚乳酸-聚乙交酯 (50：50)；聚乙交酯和聚乳酸-共聚乙交酯 聚乙交酯。在制备后，丁丙诺啡微囊 将评估颗粒大小分布、效率 包封率、微囊得率、药物释放动力学和 降解动力学。微胶囊的表面形态将 通过扫描电子显微镜进行评价。的稳定性 微胶囊将在0、15、20、25和30岁时进行长达一年的监测 C。

APPLICANT'S ABSTRACT: One of the current treatments for opiate addiction is to use opiate antagonists which generally have chemical structures similar to those of opiates. The treatment of opiate addiction requires the use of these drugs over an extended period of time. For several years, methadone, naltrexone, and buprenorphine have been used for the treatment of opiate dependent individuals. Sustained release preparations of these drugs will have an advantage over current dosage forms, which require dosing daily or three times a week. Thus, the development of a biodegradable delivery system of an opiate antagonist capable of maintaining a therapeutically useful plasma concentration is recognized as an important area of research. Sustained release microcapsules using biodegradable polymers have been developed for numerous therapeutic agents. However, the present microcapsule technology consisting of a single drug dispersed within a polymer matrix has several drawbacks. One of these drawbacks is the so called "burst effect". This is due to the rapid release of the drug which becomes trapped within the surface of the polymer during the manufacturing process. Once this rapid release has stopped, the microcapsules are able to release the drug at a fairly constant rate, as is usually desirable. This "burst effect" could be minimized by exploiting the phenomenon of phase separation between two immiscible polymers dissolved in a mutual solvent. The second polymer would provide a protective coating over the drug/polymer matrix. This one-step process would provide a consistent coating of even very small nanoparticles and would help to smooth out by lessening the "burst effect". These double-walled microcapsules will be prepared using the following biodegradable polymer combinations: polylactide and polystyrene; polylactide and polylactide-co-glycolide (50:50); polylactide and polyglycolide; polystyrene and polylactide-co-glycolide (50:50); polyglycolide and polylactide-co-glycolide; polystyrene and polyglycolide. Following the preparations, buprenorphine microcapsules will be evaluated for particle size distribution, efficiency of encapsulation, yield of microcapsules, drug release kinetics and degradation kinetics. The surface morphology of the microcapsules will be evaluated by scanning electron microscope. The stability of microcapsules will be monitored up to one year at 0, 15, 20, 25, and 30 C.