SUBDERMAL DELIVERY SYSTEMS FOR NARCOTIC ANTAGONISTS

从合成聚合物的受控药物递送是一种复杂的 药物给药方法，具有潜在的应用 研究和治疗药物滥用。为了便于从头开始 我们将继续探索各种方法， 估计药物在聚合物中的扩散率。 重点将 放置在识别装置上， 可以控制聚合物的降解性。为此中央 聚合物共混物、嵌段共聚物和共轭酸的性质 基地将被确定。扩散系数（D） 将测量一系列肽衍生物以建立 不同聚合物的D对药物MWt的依赖性。 制备和测试了L-1的一周递送系统， 美沙酮将通过测定L-美沙酮血液完成 在小鼠中的水平和功效评价。 过去的战略是 开发这种输送系统将适用于纳洛酮： 目标将是零订单交付纳洛酮，3毫克/天， 大约1个月。 微胶囊将由以下物质制备： 左旋乳酸聚酯的ε-共聚物和共混物， 羟基乙酸和ε-己内酯，所述组合物 操作以优化纳洛酮递送速率， 聚合物降解 在体外研究后， 将在体内进行测试。 麻醉药输送系统的可行性研究 拮抗剂，它是由吗啡的出现激活， 循环系统将继续。亲和力常数， 抗吗啡抗体结合的动力学和可逆性 交联脂肪族聚合物表面的吗啡残基 δ-戊内酯和ε-己内酯的聚酯将 测定 改变间隔臂和密度的影响 吗啡残留量将被确定。模型研究 间隔臂对半抗原可及性的影响 使用氮氧自旋标记进行。抗体的作用 交联脂肪酸的酶促表面侵蚀结合 聚酯，和伴随的释放纳洛酮，将是 在大鼠中测量。

Controlled drug delivery from synthetic polymers is a sophisticated method of drug administration, with potential application in the study and treatment of drug abuse. To facilitate the ab initio design of delivery systems, we will continue to explore methods of estimating the diffusivity of drugs in polymers. Emphasis will be placed on identifying means by which the permeability and degradability of polymers can be manipulated. To this end, the properties of polymer blends, block copolymers, and conjugate acids and bases will be determined. The diffusion coefficients (D) of a series of peptide derivatives will be measured to establish the dependence of D on the drug MWt for different polymers. The preparation and testing of a one week delivery system for L- methadone will be completed with determination of L-methadone blood levels and evaluation of efficacy in mice. The strategy used to develop this delivery system will be applied to naltrexone: the objective will be zero order delivery of naltrexone, 3 mg/day, for approximately 1 month. Microcapsules will be prepared from epsilon-copolymers and blends of polyesters of L-Tactic acid, glycolic acid and epsilon-caprolactone, the composition being manipulated to optimize the naltrexone delivery rate and the polymer degradation. After in vitro studies, the delivery system will be tested in vivo. Studies of the feasibility of a delivery system for narcotic antagonists that is activated by the appearance of morphine in the circulatory system will be continued. The affinity constant, kinetics, and reversibility of anti-morphine antibody binding to morphine residues at the polymer surface of crosslinked aliphatic polyesters of delta-valerolactone and epsilon-caprolactone will be determined. The effects of changing the spacer arm and the density of morphine residues will be determined. Model studies of the effect of the spacer arm on the accessibility of the hapten will undertaken using a nitroxide spin label. The effect of antibody binding on the enzymatic surface erosion of cross-linked aliphatic polyesters, and the concomitant release of naltrexone, will be measured in rat.