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: 9891431
• 负责人: Ryan Donnelly
• 金额: $ 83.35万
• 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 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9891431
• 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 environment; 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.

项目摘要 微阵列贴片（MAPs），也称为微针贴片，是一种新型的无针递送 用于药物和疫苗的技术。地图包含一系列溶解的微米级 突出，并适用于像绷带，无痛刺穿角质层，以促进 皮内给药由于其易于使用和可接受性，MAP可能会提高依从性 治疗，尤其是儿童。 我们建议开发一种含有长效抗逆转录病毒药物的MAP， 治疗儿童HIV感染的药物递送系统，特别关注年轻人的适用性 孩子MAP的设计要求佩戴时间短（少于1小时）， 药物提供每月（或频率较低）给药方案。与其他长效剂量相比 MAP的形式，如注射剂和植入剂，将是无痛的，可以在家里管理 由父母或看护者。 该项目的第一阶段将侧重于确定儿科MAP要求， 抗逆转录病毒MAP制剂。在头两年，项目小组计划： 1.确定目标产品概况目标和首选用户特征，确定利益相关者的需求， 并评估潜在的可接受性，以告知产品开发。 2.通过基于生理学的药代动力学建模确定MAP参数。 3.设计、制造和表征纳米悬浮液负载的溶解MAP。 假设第一阶段的结果令人鼓舞，在项目的第二阶段，我们将重点关注 在临床前和最终用户研究中验证MAP性能。在过去的三年里，项目组 计划： 4.评估体内药物递送和药代动力学外推。 5.评估非人灵长类动物的药代动力学和抗病毒疗效。 6.对MAP原型进行以用户为中心的设计开发，进行风险分析， 最终用户的可接受性。