MAPs for Peds: Development of a Microarray Patch for Delivery of Long-Acting Antiretrovirals for Treatment of Pediatric HIV Infection

儿童 MAP：开发用于递送长效抗逆转录病毒药物以治疗儿童 HIV 感染的微阵列贴片

• 批准号: 10546215
• 负责人: Robert Kwai Ming Choy
• 金额: $ 94.06万
• 依托单位: PATH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-16 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10546215
• 关键词: Adherence; Adolescent; Age; Anatomy; Animal Model; Anti-Retroviral Agents; Bandage; Caregivers; Characteristics; Child; Childhood; Development; Dosage Forms; Dose; Drug Delivery Systems; Drug Kinetics; Ensure; Family suidae; Formulation; Geometry; HIV; Health; Height; Home; Hour; Human; Implant; In Vitro; Infant; Injectable; International; Interview; Intramuscular Injections; Kinetics; Macaca; Maintenance; Measures; Needles; Neonatal; Oral; Outcome; Output; Painless; Parents; Performance; Pharmaceutical Preparations; Phase; Physiological; Plasma; Polymers; Process; RNA-Directed DNA Polymerase; Rattus; Regimen; Risk; Route; Safety; Sampling; Skin; Solid; Standardization; Stratum corneum; Target Populations; Technology; Time; Vaccines; Viral; Virus; Work; age group; anti-viral efficacy; antiretroviral therapy; aqueous; base; clinically relevant; design; drug development; efficacy study; engineering design; hazard; improved; in vivo; nanoparticle drug; non-drug; nonhuman primate; novel; pediatric human immunodeficiency virus; pediatric human immunodeficiency virus infection; pediatric patients; pharmacokinetic model; pre-clinical; product development; prototype; service delivery; simian human immunodeficiency virus; user centered design

PROJECT SUMMARY Microarray patches (MAPs), also known as microneedle patches, are a novel, needle-free delivery technology in development for drugs and vaccines. MAPs contain an array of dissolving micron-scale projections and are applied like a bandage, painlessly piercing the stratum corneum to facilitate intradermal delivery. Due to their ease of use and acceptability, MAPs can potentially improve adherence to treatment, particularly for children. We propose to develop a MAP containing long-acting antiretrovirals as an age-appropriate, long-acting drug delivery system to treat pediatric HIV infection, with a particular focus on suitability for use in young children. The MAP would be designed to require a short wear time (less than 1 hour) and deliver enough drug to provide a monthly (or less frequent) dosing regimen. In contrast to other long-acting dosage forms, such as injectables and implants, the MAP would be painless and could be administered at home by parents or caregivers. The first phase of the project will focus on defining pediatric MAP requirements and optimizing antiretroviral MAP formulations. In the first two years, the project team plans to: 1. Define target product profile targets and preferred user characteristics, identify stakeholder needs, and evaluate potential acceptability to inform product development. 2. Determine MAP parameters through physiologically-based pharmacokinetic modeling. 3. Design, manufacture, and characterize nanosuspension-loaded dissolving MAPs. Assuming promising results from the first phase, during the second phase of the project we will focus on verifying MAP performance in preclinical and end user studies. In the last three years, the project team plans to: 4. Assess in vivo drug delivery and pharmacokinetic extrapolation. 5. Assess pharmacokinetics and antiviral efficacy in non-human primates. 6. Conduct user-centered design development of MAP prototypes, conduct a risk analysis, and assess end user acceptability.

项目总结 微阵列贴片(MAP)，也称为微针贴片，是一种新型的无针递送方式 药物和疫苗开发中的技术。地图包含一组可分解的微米级 突出物和绷带一样贴着，无痛地刺穿角质层，方便 皮内给药。由于地图的易用性和可接受性，地图可能会提高遵从性 特别是对儿童的治疗。 我们建议开发一种包含长效抗逆转录病毒药物的MAP，作为一种适合年龄的长效 治疗儿童艾滋病毒感染的药物输送系统，特别注重适合年轻人使用 孩子们。地图将被设计为需要较短的磨损时间(不到1小时)并提供足够的信息 提供每月(或不太频繁)给药方案的药物。与其他长效剂量不同 通过注射和植入物等形式，映射将是无痛的，可以在家中进行 由父母或照顾者。 该项目的第一阶段将侧重于确定儿科地图要求和优化 抗逆转录病毒MAP制剂。在头两年，项目组计划： 1.定义目标产品简介目标和首选用户特征，确定利益相关者需求； 并评估潜在的可接受性，以便为产品开发提供信息。 2.通过基于生理的药代动力学模型确定MAP参数。 3.设计、制造和表征纳米悬浮液加载的溶解图谱。 假设第一阶段取得了有希望的结果，在项目的第二阶段，我们将重点放在 在临床前和终端用户研究中验证MAP的性能。在过去的三年里，项目团队 计划： 4.评价体内给药和药代动力学外推。 5.评估非人灵长类动物的药代动力学和抗病毒疗效。 6.以用户为中心进行地图原型设计开发，进行风险分析，评估 最终用户的可接受性。