Therapeutics Core (Page 286)

治疗核心（第286页）

• 批准号: 8436273
• 负责人: Howard E Gendelman
• 金额: $ 17.41万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8436273
• 关键词: AIDS neuropathy; AIDS/HIV problem; Address; Aging; Anti-Retroviral Agents; Biological Availability; Biological Models; Cells; Central Nervous System Agents; Chronic; Delayed-Action Preparations; Development; Dose; Drug Delivery Systems; Drug Formulations; Foundations; Goals; HIV; HIV Infections; Immune; Injectable; Instruction; Investigation; Laboratory Animal Models; Lead; Modeling; Monkeys; Mus; Nervous system structure; Neuraxis; Neurodegenerative Disorders; Penetrance; Pharmaceutical Preparations; Research; Research Personnel; Safety; Testing; Therapeutic; Therapeutic Agents; Therapeutic Intervention; Tissues; Viral; Water; Work; antiretroviral therapy; bench to bedside; combat; human disease; improved; monocyte; nanoformulation; novel; response; success

PR0JECT SUMMARY (See instructions): The goals of the Therapeutics core are to provide nanoformulations to invesfigators pursuing nanoformulated ntiretroviral and neuroprotective therapies for increased central nervous system (CNS) penetrance. The formulations developed address how monocytes and other immune cells may be harnessed for drug delivery. Before such novel therapies can be administered to people, we will determine, in well-validated laboratory and animal models, the optimal doses and formulation administration. The crux of the problem facing the Core, namely can nanoformulated antiretroviral therapy show sustained antiretroviral responses and slow release of drug in tissues, has now been addressed. The Core addresses a specific and important issue in the treatment of HIV and neuroAIDS, with broader implications for therapeutic interventions to other neurodegenerative diseases. Through this project, we will identify and manufacture candidate Nanoformulations of currently used efficacious antiretrovirals. These will be tested model systems of human disease, ranging from cultured monocytes to mice to monkeys, to examine pharmacokinefic, safety and efficacy. This Core, overall, represents work that may prove to be a major advance in the development of long-lasting therapeutic agents that can lead to real treatments both systemic and CNS human disease.

概要（参见说明）： Therapeutics核心的目标是为追求纳米抗逆转录病毒和神经保护疗法的研究者提供纳米制剂，以增加中枢神经系统（CNS）的抗逆转录病毒能力。开发的制剂解决了单核细胞和其他免疫细胞如何用于药物递送。在这种新疗法可以施用于人之前，我们将在经过充分验证的实验室和动物模型中确定最佳剂量和制剂施用。核心所面临的问题的关键，即纳米抗逆转录病毒疗法能否显示持续的抗逆转录病毒反应和药物在组织中的缓慢释放，现在已经得到解决。核心解决了艾滋病毒和神经艾滋病治疗中的一个具体而重要的问题，对其他神经退行性疾病的治疗干预具有更广泛的意义。通过这个项目，我们将确定和生产候选纳米目前使用的有效的抗逆转录病毒药物。这些将是人类疾病的测试模型系统，从培养的单核细胞到小鼠到猴子，以检查药物代谢、安全性和有效性。总体而言，该核心代表了可能被证明是开发长效治疗剂的重大进展的工作，这些治疗剂可以导致真实的治疗全身性和CNS人类疾病。