Controlled Delivery System for Naltrexone

纳曲酮控释系统

• 批准号: 6700302
• 负责人: EMMANUEL O AKALA
• 金额: $ 15.1万
• 依托单位: HOWARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6700302
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse chemotherapy; biodegradable product; bioengineering /biomedical engineering; chemical synthesis; dosage forms; drug delivery systems; drug design /synthesis /production; high performance liquid chromatography; laboratory rat; male; microcapsule; naltrexone; nanotechnology; narcotic antagonists; pharmacokinetics; polymers; scanning electron microscopy; slow release drug; subcutaneous drug administration; transmission electron microscopy

DESCRIPTION (provided by applicant): The importance of the problem of alcoholism is shown by the report which indicates that approximately 7.5 percent of the U.S. population (about 14 million Americans) abuse and/or are dependent on alcohol. Alcohol-related deaths account for about five percent of all deaths in the U.S. Aside from human suffering, which is difficult to quantify, it is estimated that alcohol dependence costs the society about 116 billion dollars per year. There are medical complications from alcohol dependence: cardiovascular, neurological, gastrointestinal, immunologic, psychiatric, and obsteric complications. The main approaches to the treatment of alcoholism include detoxification, non-pharmacological, (psychosocial) treatment methods, and pharmacotherapy. The effectiveness of psychosocial treatment approaches has not been established: they have met with little or no success in treating alcoholism. The focus of medication development for addictive disorders, such as alcoholism, has moved from withdrawal to relapse prevention. The effectiveness of naltrexone (already approved by the Food and Drug Administration (FDA) is limited by problem with compliance: alcoholics show particularly low rates of medication compliance. Moreover, naltrexone is a highly extracted drug, with a low amount of the parent drug available in the brain. Consequently, there is need for the development of a controlled delivery system which can, not only sustain the release of the drug for a long time, but can maintain a constant blood level by releasing the drug at a constant rate at the site of absorption. If the delivery system is injectable, naltrexone can escape the first pass effect in the liver. In our preliminary studies, we have developed polymeric injectable nano- and microparticulate naltrexone controlled delivery systems capable of sustaining in vitro availability of naltrexone for a period greater than three months. Our goal is sustained delivery of naltrexone for six to twelve months. Synthesis of biodegradable and biocompatible copolymers and their use in optimizing the fabrication of naltrexone controlled delivery systems and their evaluation in rats are the focus of this proposal. The use of controlled release naltrexone preparations will ensure compliance because the need for the patient to decide to take his medication would be minimized; it may also increase the likelihood of a therapeutic response by yielding a more predictable and constant plasma concentration of the parent drug and making it available in the brain.

描述（由申请人提供）：问题的重要性

项目成果

Disposition of naltrexone after intravenous bolus administration in Wistar rats, low-alcohol-drinking rats and high-alcohol-drinking rats.

• DOI: 10.1159/000159776
• 发表时间: 2008
• 期刊: Neuropsychobiology
• 影响因子: 3.2
• 作者: Akala EO;Wang H;Adedoyin A
• 通讯作者: Adedoyin A