LASER ART for PreP

PreP 激光艺术

基本信息

批准号：
10259156
负责人：
Benson Edagwa
金额：
$ 71.02万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-12 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10259156
关键词：
AIDS prevention Adherence Adverse event Animal Model Animals Anti-Retroviral Agents Area Arts Biological Availability Biological Models CD4 Positive T Lymphocytes Cell Count Cells Characteristics Chemicals Chemistry Conscious Creativeness Data Data Set Development Dose Drug Design Drug Formulations Drug Kinetics Drug or chemical Tissue Distribution Esterification Esters Female Formulation Freeze Drying Frequencies Funding Future Gap Junctions Goals HIV Infections HIV-1 Half-Life Health Healthcare Hematology Histology Human Hydrolysis Hydrophobicity Immunologics Individual Industry Infection Injections Interdisciplinary Study Intramuscular Injections Investigational New Drug Application Laboratories Lasers Lead Letters Life Link Lipids Macaca mulatta Measures Medicine Metabolic Modification Mus Names Nebraska Nucleotides Pathway interactions Penetrance Personal Satisfaction Pharmaceutical Preparations Pharmacodynamics Pharmacologic Substance Pharmacology Pharmacy (field)Plants Plasma Powder dose form Preclinical Testing Prevention Process Prodrugs Production Publications Publishing Quality Control Rattus Reproducibility Research Research Design Research Personnel Research Project Grants Rest Reticuloendothelial System Rodent Safety Savings Scheme Science Scientist Sex Differences Site Substance Use Disorder Suspensions Tenofovir Test Result Testing Tissues Toxicology Treatment Protocols United States Food and Drug Administration Universities Validation Viral Load result Viral reservoir Virus Virus Replication Work antiretroviral therapy base bench to bedside biomaterial compatibility chemical synthesis cost design disease transmission drug modification emtricitabine expectation high risk humanized mouse improved innovation interdisciplinary approach large scale production lipophilicity macrophage male multidisciplinary nanocrystal nanoformulation nanomedicine novel novel strategies nucleoside monophosphate particle pharmacokinetics and pharmacodynamics pill pre-exposure prophylaxis prevent product development scale up surfactant tool translational study uptake viral resistance viral transmission virology

项目摘要

Abstract This project contains a highly collaborative investigative team with interdisciplinary expertise with significant potential impact for HIV/AIDS prevention. The proposal includes pharmacologic, virologic, animal and product development studies designed to halt disease transmission through novel long-acting (LA) antiretrovirals. These are named LA slow effective release antiretroviral therapies (LASER ART) designed to facilitate HIV-1 prevention by intense bench to the clinic translational studies. Innovative interdisciplinary approaches contain a detailed research plan, extensive preliminary and broadly published supportive data. Creativity and innovativeness are offered placed at higher risk than a conventional research project. The work builds on the development of parenteral nanoformulations of chemically modified antiretroviral drugs designed to improve adherence. The drugs are currently offered once/day in pill form but will be converted to up to once a year administration. Support from expert pharmacologists and pharmaceutical scientists with University researchers are operative. The drugs include dolutegravir (DTG), emtricitabine (FTC) and tenofovir (TFV) created to extend their apparent drug half-life, efficacy and abilities to target viral reservoirs. They are, in measure, DTG and FTC and TFV prodrug + nucleotide (ProTides) designated “N” for nanoformulation, “M” for esterification and “P” for ProTides. The created NPFTC and NPTFV and NM2DTG demonstrate sustained plasma and tissue drug concentrations of > 90% inhibitory concentration from months to a year. Based on encouraging results, we seek funds to facilitate large scale development that would facilitate future human studies. The final formulations would be characterized by sustained prodrug hydrolysis with reduced injection volumes. The pathway forward follows established partnership with the Clinton Health Access Initiative and oversight by ViiV Healthcare and Gilead Sciences. The overarching goal is safety, reproducibility and “scale-up” that follows US Food and Drug Administration-approved current good manufacturing practices (cGMP). The specific aims are each supported by extensive published data sets forged through the multidisciplinary research. Creation and characterization focus on prodrug formulations, toxicology, and pharmacokinetics profiles follow a safe developmental action plan. The work is facilitated by a fully operational cGMP facility and rhesus macaque validations. The lead formulation will be developed with our CHAI partners. We posit that the creation of LASER ART DTG or FTC and TFV will have a profound impact on HIV prevention.

抽象的该项目包含一个高度协作的调查团队，跨学科专家具有重要的对艾滋病毒/艾滋病预防的潜在影响。该提案包括药理，病毒，动物和产品开发研究旨在通过新型长效（LA）抗逆转录病毒停止疾病的传播。这些被命名为LA缓慢释放抗逆转录病毒疗法（激光ART），旨在促进HIV-1 强烈的基准预防诊所翻译研究。创新的跨学科方法包含详细的研究计划，广泛的初步和广泛发布的支持数据。创造力和与传统研究项目相比，提供的创新性具有更高的风险。作品建立在旨在改善的化学修饰抗逆转录病毒药物的父母纳米制造的开发坚持。这些药物目前每天以药丸形式提供一次，但每年最多可转换一次行政。大学研究人员的专家药理学家和药学科学家的支持正在运行。这些药物包括Dolutegravir（DTG），Emtricitabine（FTC）和Tenofovir（TFV），以扩展他们明显的药物半衰期，效率和针对病毒储层的能力。它们是在测量中，DTG和FTC 和TFV前药 +核苷酸（蛋白酶）指定为纳米成型的“ N”，用于酯化的“ M”，用于“ P”，用于“ P” protides。创建的NPFTC和NPTFV和NM2DTG表现出持续的血浆和组织药物从月到一年的抑制浓度> 90％。基于令人鼓舞的结果，我们寻求资金来托管大规模发展，以托管未来的人类研究。决赛公式将以持续的前药水解为特征，并减少注射体积。这前进的途径是在与克林顿健康访问计划和VIIV的监督的建立伙伴关系之后医疗保健和吉利德科学。总体目标是安全性，可重复性和跟随我们的“扩展” 食品和药物管理局批准的当前良好制造实践（CGMP）。具体目的是每个人都在多学科研究中忘记了大量已发表的数据集的支持。创造和表征着重于前药公式，毒理学和药代动力学概况，安全发展行动计划。这项工作是由完全运行的CGMP设施和恒河猴准备的验证。铅配方将与我们的柴合作伙伴一起开发。我们指出的是激光ART DTG或FTC和TFV将对预防HIV产生深远的影响。