An Implantable Semiannual Antipsychotic Delivery System

植入式半年一次抗精神病药物输送系统

基本信息

批准号：
8197709
负责人：
STEVEN J SIEGEL
金额：
$ 39万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-12-15 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8197709
关键词：
Absorbable Implants Advanced Development Adverse effects Adverse event Affect Affinity Amphetamines Animal Model Antipsychotic Agents Attenuated Behavior Behavioral Binding Biochemical Blood Brain Catalepsy Chemistry Chronic Clinical Data Development Dopamine Dose Environment Enzymes Event-Related Potentials Family Fostering Funding GTP-Binding Proteins Generations Glucose Glycolic-Lactic Acid Polyester Goals Health Implant In Vitro Infusion procedures Intervention Ligands Liver Long-Term Effects Measures Medicine Messenger RNA Metabolism Modeling Molecular Motor Motor Activity Mus Neurons Oral Oral Administration Outcome Patients Pattern Performance Pharmaceutical Preparations Placebos Polymers Prolactin Proteins Quality of life Rattus Relapse Relative (related person)Risperidone Rodent Saline Schizophrenia Second Messenger Systems Serotonin Serum Signal Transduction Social Interaction Sterility Synapses System Testing Therapeutic Time Variant Western Blotting behavior measurement biodegradable polymer conditioned fear improved in vivo medication compliance novel object recognition prepulse inhibition protein activation public health relevance receptor receptor expression receptor function safety net second messenger

项目摘要

DESCRIPTION (provided by applicant): Rationale: Medication nonadherence is the highest determinant of relapse in schizophrenia. Interventions that help patients remain on medication for extended periods could substantially improve clinical outcomes. Significance: The revised R01 renewal application will advance the development of an implantable long-term risperidone delivery system to improve medication adherence in schizophrenia. Achieving this goal could improve the health and quality of life for millions of people with schizophrenia and their families. Progress: We completed both Aims during the previous period by performing in vitro-in vivo correlation (IVIVC) modeling for sterile, biodegradable implants. In the previous 2-year funding period, we developed a long-term risperidone delivery system using the biodegradable polymer poly-lactide-co-glycolide (PLGA). First, we determined in vitro risperidone release from multiple types of implants by varying lactide to glycolide ratios. We then determined in vivo serum risperidone concentration from a New Hypothesis: We propose that the benefits of long term delivery systems extend beyond a safety net against relapse. Preliminary data suggest that steady state infusion of antipsychotic medication from implants could provide consistent modulation of dopaminergic tone intermittent oral administration allowing the brain to remodel in a stable therapeutic environment. Studies in this application would test this hypothesis using animal models of antipsychotic efficacy and side effects. Proposed Studies: The current application would determine how constant risperidone infusion from implants affects behavioral (Aim 1), biochemical (Aim 2) and molecular (Aim 3) measures of efficacy and side effects comparison to three times daily oral administration in rodents. PUBLIC HEALTH RELEVANCE: Medication nonadherence is the highest cause of relapse in schizophrenia. Interventions that help patients remain on medicine would substantially improve quality of life for millions of patients and their families. We will advance the development of an implantable long-term antipsychotic delivery system to improve medication adherence in schizophrenia. We will also determine how constant infusion of antipsychotic medication from implants improves behavior and brain function in comparison to oral administration rodents.

描述（由申请人提供）：理由：不遵守药物是精神分裂症中复发的最高决定因素。帮助患者长期服用药物的干预措施可以大大改善临床结果。意义：修订后的R01更新应用将推动开发可植入的长期利培酮递送系统，以改善精神分裂症的药物依从性。实现这一目标可以改善数百万人精神分裂症及其家人的健康和生活质量。进度：我们在上一个时期完成了两个目标，通过对无菌，可生物降解的植入物进行体外体内相关（IVIVC）建模。在前两年的资金期间，我们使用可生物降解的聚合物聚合物聚合物 - 糖糖苷（PLGA）开发了长期利培酮递送系统。首先，我们通过改变乳酸和糖苷比例来确定体外利培酮从多种类型的植入物中释放出来。然后，我们从一个新的假设中确定体内血清利培酮的浓度：我们建议长期递送系统的好处超出了安全网，而不是复发。初步数据表明，从植入物中稳态输注抗精神病药物可以提供多巴胺能张力的间歇性口服给药的一致调节，从而使大脑在稳定的治疗环境中重塑。该应用中的研究将使用抗精神病药和副作用的动物模型检验该假设。拟议的研究：当前的应用将确定植入物的恒定利培酮输注如何影响行为（AIM 1），生化（AIM 2）和分子分子（AIM 3）疗效和副作用的测量值与啮齿动物的每日口服三次。公共卫生相关性：药物不遵守是精神分裂症复发的最高原因。帮助患者继续服药的干预措施将大大改善数百万患者及其家人的生活质量。我们将发展一个可植入的长期抗精神病药递送系统，以改善精神分裂症的药物依从性。我们还将确定与口服啮齿动物相比，植入物中抗精神病药的持续输注如何改善行为和大脑功能。