Development and Evaluation of Dual Compartment Combination Microbicides

双室组合杀菌剂的开发与评价

• 批准号: 8374028
• 负责人: Robert Walter Buckheit
• 金额: $ 322.4万
• 依托单位: IMQUEST BIOSCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-22 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8374028
• 关键词: Development; Evaluation; Dual; Compartment; Combination

We propose to bring a well-established team of Investigators with diverse multidisciplinary backgrounds in virology, toxicology, clinical infectios disease, pharmacology, pharmaceutics, physiology, psychology/behavioral science, materials science, and biomedical engineering to develop a combination microbicide product formulated for delivery to both the vaginal and the colorectal compartments. The rationally designed products will include dual compartment gels (DuoGels) and Smart Suppositories that will function as delivery vehicles for two highly potent antiretroviral agents - tenofovir and IQP-0528. Our program will integrate in vitro and ex vivo evaluations of product efficacy, safety, pharmacokinetics and pharmacodynamics, as well as PK/PD/safety/efficacy evaluations in nonhuman primates and pre-Phase 1 safety and PK studies in humans. Our proposal also incorporates advancements in microbicide science, including the development of a novel in vitro method for determination of API dosing levels, behavioral studies extended to the rectal compartment and dual compartment products, and imaging and modeling that will enhance our ability to predict the interactions between formulated microbicide products, virus, biological matrices, and target fluids and tissue in the vagina and rectum. Our project will culminate in the creation of effective and acceptable, dual compartment use gels (DuoGels) and solid dosage vehicles (Smart Suppositories) for clinical development. We will create and apply advanced means to formulate and deliver these novel compounds (alone or in combinations) in coitally-dissociated ways. Pursuit of the two different delivery modalities (DuoGels versus Smart Suppositories) will account for both differences in microbicide functionality against HIV-1 and different product preferences amongst women. The time course of product development will include concomitant studies that define acceptability to women and men, so that cooptimization of biological functionality and behavioral acceptability is achieved. Through our industrial partnership with ImQuest Pharmaceuticals our methodology and products will have an immediate outlet to further clinical development.

我们建议携带一个成熟的研究人员团队，具有多种多样的多学科背景，毒理学，毒理学，临床感染疾病，药理学，药理学，药物学，生理学，心理学/行为科学，材料科学和生物医学工程，以开发组合微生物剂产物，以供应到阴道主义和色素构成。理性设计的产品将包括双隔室凝胶（Duogels）和智能栓剂，这些栓剂将用作两种高效抗逆转录病毒剂的运输车辆-Tenofovir和IQP -0528。 我们的计划将在非人类灵长类动物和人类中的相遗传学和相期前的安全和PK研究中对产品疗效，安全性，药代动力学和药效学以及PK/PD/安全/效率评估的体外评估进行整合。我们的建议还纳入了杀菌剂科学的进步，包括开发一种新型的体外方法，用于确定API给药水平，行为研究扩展到直肠室和双隔室产品，以及成像和建模，从而增强了我们预测配方型微生物产物，病毒，病毒，生物矩阵和目标流体和靶心和组织的能力。我们的项目将在创建有效且可接受的双隔间使用凝胶（Duogels）和固体剂量车（智能栓剂）进行临床开发方面达到顶峰。我们将创建和应用先进的手段，以共同划分的方式制定和传递这些新颖的化合物（单独或组合）。追求两种不同的交付方式（Duogels vess smart Supsitories）将构成对HIV-1的菌心功能的差异，以及女性中不同产品的偏好。产品开发的时间过程将包括伴随的研究，以定义男女的可接受性，以便实现生物功能和行为可接受性的合作。通过与Imquest Pharmaceuticals的工业合作伙伴关系，我们的方法论和产品将立即提供进一步的临床开发。