Long-acting multi prevention implant for 2-year contraception and HIV PrEP
用于 2 年避孕和 HIV PrEP 的长效多重预防植入物
基本信息
- 批准号:10619811
- 负责人:
- 金额:$ 83.07万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-04-01 至 2028-03-31
- 项目状态:未结题
- 来源:
- 关键词:AIDS preventionAcquired Immunodeficiency SyndromeAddressAdherenceAdoptedAgeAnti-Retroviral AgentsCause of DeathClinicalCold ChainsContraceptive AgentsContraceptive methodsDapivirineDeveloping CountriesDiffusionDoseDrug CombinationsDrug Delivery SystemsDrug KineticsDrug StabilityEtonogestrelExhibitsFDA approvedFormulationFutureGoalsHIVHIV InfectionsHIV antiretroviralHealthHormonalHumanImplantIndividualIon ChannelKineticsLeadMacaca nemestrinaMaternal MortalityMembraneMethodsModernizationOralPeripheral Blood Mononuclear CellPharmaceutical PreparationsPharmacodynamicsPharmacologyPolymersPositioning AttributePregnancyPreventionPrevention strategyPreventiveProdrugsProgestinsPumpRattusRecommendationRegimenReproductive HealthResearchResistanceRetrievalRiskSafetyScanning Electron MicroscopySexual HealthStigmatizationStructureTailTechnologyTestingTissuesVaginaVaginal RingVirus DiseasesWomanWorkWorld Health Organizationclinical developmentclinical translationcontraceptive efficacydesigndrug release kineticsefficacy evaluationexperiencehormonal contraceptionhydrophilicityimplantable deviceimplantationimprovedinnovationlow and middle-income countriesnanochannelnanofluidicnext generationnonhuman primatepatient orientedpharmacodynamic modelpillpre-clinicalpre-exposure prophylaxispreferencepregnancy preventionprophylacticpublic health relevancereproductiveresponsesexually activesimian human immunodeficiency virussocial stigmasubcutaneoustechnology platformunintended pregnancyuptakeviral transmission
项目摘要
PROJECT SUMMARY/ABSTRACT
Maternal mortality and AIDS are among the leading causes of death in reproductive-age women globally due to
unintended pregnancy and the disproportionate burden of HIV infection. While effective prevention methods
exist, only 21% of women have access to modern contraceptives and adherence to HIV PrEP regimen is poor
in many HIV-endemic regions. Multipurpose prevention technologies (MPT) aim to synchronize contraceptive
delivery with HIV PrEP, offering a patient-centered approach to provide dual coverage to sexually active women
in a single product. A long-acting unified delivery product that can be administered in a discreet manner could
reduce stigma around contraceptives and HIV PrEP, thereby improving uptake and adherence to combination
prevention products. Our goal is to develop a long-acting delivery implant of etonogestrel (ENG) and islatravir
(ISL) drugamer with an unprecedented 2-year release duration for pregnancy and HIV prevention that eliminates
further need of adherence. A new subcutaneous nanofluidic multipurpose implant (NanoMPI) will be brought
together with a new polymeric prodrug technology termed “drugamer”, to achieve this innovative product
candidate that delivers ultra-long acting ENG+ISL drug dosing durations. The NanoMPI leverages a nanofluidic
membrane with nanochannels and a single drugamer reservoir to achieve zero-order release kinetics through
passive diffusion without pumping mechanisms, permitting discreet, user-independent dosing. Key product
attributes will include drug stabilization on the multi-year timeframe, minimized early- and late-stage burst release
and pharmacokinetic (PK) tailing, zero-order drug release kinetics tailored to the individual drug PK/PD
(pharmacodynamic) requirements, user-independent dosing, and retrievability. The project is structured around
3 specific aims: 1) to develop optimized ENG-ISL drugamer formulations that stabilize the drugs and exhibit the
desired zero order release profiles, in concert with the optimization of the NanoMPI device for 2-year sustained
release; 2) to assess pharmacokinetics, tolerability, and safety of the lead ENG-ISL NanoMPI device for 2 years
in pigtail macaques; and 3) to evaluate contraception and HIV PrEP efficacy of ENG-ISL NanoMPI in pigtail
macaques via repeated low-dose vaginal challenge and develop a PK/PD model. We will use a milestone-driven
research approach to advance the ENG-ISL NanoMPI technology towards the ultimate goal of clinical translation,
leveraging the interdisciplinary team’s experience in drugamer technology, drug delivery, pre-clinical and clinical
HIV prevention studies, and hormonal contraceptive and antiretroviral pharmacology. Importantly, the NanoMPI
addresses user preferences for a dual prevention product, discretion and longer dosing duration. Successful
completion will generate a versatile MPT platform that could be adopted for other drug combinations and
preventative strategies.
项目概要/摘要
孕产妇死亡率和艾滋病是全球育龄妇女死亡的主要原因之一
意外怀孕和艾滋病毒感染造成的负担不成比例,同时采取有效的预防方法。
存在,只有 21% 的女性能够获得现代避孕药具,并且 HIV PrEP 方案的依从性较差
在许多艾滋病毒流行地区,多用途预防技术(MPT)旨在同步避孕。
HIV PrEP 分娩,提供以患者为中心的方法,为性活跃的女性提供双重覆盖
可以以谨慎的方式施用的长效统一递送产品。
减少避孕药具和 HIV PrEP 的耻辱感,从而提高组合用药的采用率和依从性
我们的目标是开发依托孕烯 (ENG) 和 islatravir 的长效递送植入物。
(ISL) 药物制造者,具有史无前例的 2 年释放期,用于怀孕和艾滋病毒预防,消除了
将带来新的皮下纳米流体多用途植入物(NanoMPI)的进一步需求。
与称为“drugamer”的新型聚合物前药技术一起,实现了这一创新产品
NanoMPI 利用纳米流体提供超长效 ENG+ISL 药物给药持续时间。
具有纳米通道和单个药物储存器的膜,通过以下方式实现零级释放动力学
无泵送机制的被动扩散,允许谨慎、独立于用户的剂量关键产品。
特性将包括多年时间框架内的药物稳定性、最大限度地减少早期和晚期突释
和药代动力学 (PK) 拖尾、针对单个药物 PK/PD 定制的零级药物释放动力学
(药效学)要求、独立于用户的剂量和可回收性。
3 个具体目标:1) 开发优化的 ENG-ISL 药物制剂,以稳定药物并表现出
所需的零级释放曲线,与 NanoMPI 设备的 2 年持续优化相结合
发布;2) 评估领先的 ENG-ISL NanoMPI 设备的药代动力学、耐受性和安全性,为期 2 年
在猪尾猕猴中;3) 评估 ENG-ISL NanoMPI 在猪尾中的避孕和 HIV PrEP 功效
我们将通过重复低剂量阴道挑战来研究猕猴并开发 PK/PD 模型。
研究方法推动 ENG-ISL NanoMPI 技术实现临床转化的最终目标,
利用跨学科团队在药物技术、药物输送、临床前和临床方面的经验
HIV 预防研究、激素避孕药和抗逆转录病毒药理学。重要的是 NanoMPI。
满足用户对双重预防产品、自由裁量权和更长给药持续时间的偏好。
完成后将产生一个多功能的 MPT 平台,可用于其他药物组合和
预防策略。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Alessandro Grattoni其他文献
Alessandro Grattoni的其他文献
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{{ truncateString('Alessandro Grattoni', 18)}}的其他基金
Ultra-long Acting Transcutaneously Refillable Islatravir Nanofluidic Implant for HIV Pre-Exposure
用于 HIV 暴露前的超长效经皮可再填充 Islatravir 纳米流体植入物
- 批准号:
10481727 - 财政年份:2022
- 资助金额:
$ 83.07万 - 项目类别:
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血管化胰岛移植 NICHE 结合局部免疫抑制治疗 1 型糖尿病
- 批准号:
10656255 - 财政年份:2022
- 资助金额:
$ 83.07万 - 项目类别:
Ultra-long Acting Transcutaneously Refillable Islatravir Nanofluidic Implant for HIV Pre-Exposure
用于 HIV 暴露前的超长效经皮可再填充 Islatravir 纳米流体植入物
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10605334 - 财政年份:2022
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$ 83.07万 - 项目类别:
Vascularized Islet transplantation NICHE with local immunosuppression for the treatment of type 1 diabetes
血管化胰岛移植 NICHE 结合局部免疫抑制治疗 1 型糖尿病
- 批准号:
10417410 - 财政年份:2022
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$ 83.07万 - 项目类别:
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带有局部免疫抑制的血管化 NICHE 用于细胞替代治疗 1 型糖尿病
- 批准号:
10704182 - 财政年份:2022
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$ 83.07万 - 项目类别:
Vascularized NICHE with local immunosuppression for cell replacement for Type 1 diabetes
带有局部免疫抑制的血管化 NICHE 用于细胞替代治疗 1 型糖尿病
- 批准号:
10704182 - 财政年份:2022
- 资助金额:
$ 83.07万 - 项目类别:
Vascularized NICHE with local immunosuppression for cell replacement for Type 1 diabetes
带有局部免疫抑制的血管化 NICHE 用于细胞替代治疗 1 型糖尿病
- 批准号:
10511952 - 财政年份:2022
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