Innovative 3D Printed Intravaginal Ring AnelleO-PRO, the first Single Administration of Progesterone for Infertility

创新 3D 打印阴道环 AnelleO-PRO，首个单次注射黄体酮治疗不孕症

基本信息

批准号：
10323463
负责人：
Soumya Rahima Benhabbour
金额：
$ 86.29万
依托单位：
ANELLEO, INC.
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-19 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10323463
关键词：
3-Dimensional 3D Print Accelerated Phase Address Adherence Affect Age Animal Model Assisted Reproductive Technology Atopobium vaginae Behavioral Biological Cervical Characteristics Computer-Aided Design Contraceptive methods Couples Custom Data Development Development Plans Devices Diffusion Dimensions Drug Controls Drug Delivery Systems Drug Kinetics Drug Targeting Engineering Evaluation FDA approved Fertilization in Vitro Formulation Fostering Geometry Goals Hormone replacement therapy In Vitro Infertility Injections Intramuscular Injections Investigation Link Liquid substance Macaca Macaca nemestrina Mechanics Medical Methods Modality Modeling Molds Names Pain Patients Perception Performance Pharmaceutical Preparations Pharmacodynamics Pharmacology Phase Placebos Plasma Pregnancy Preparation Process Production Progesterone Property Quality Control Regimen Resource Development Safety Schedule Sheep Site Small Business Innovation Research Grant Small Business Technology Transfer Research Solid Supplementation Surface Surface Properties Systems Development Technology Testing Tissues Toxic effect Vagina Vaginal Discharge Vaginal Gel Vaginal Ring Woman base compliance behavior controlled release cost effective design drug release kinetics global health improved in vitro testing in vivo infertility treatment innovation innovative technologies manufacturing process mechanical properties meetings multidisciplinary novel pre-clinical preference quality assurance reproductive side effect skills stability testing treatment duration vaginal fluid

项目摘要

PROJECT SUMMARY Infertility is a global health problem. In the US alone, ~1.7 million women are treated for infertility every year. To improve infertility treatment, there is a strong need to promote patient-friendly methods for progesterone supplementation in assisted reproductive technology (ART). Intravaginal rings, which are well tolerated by women, are efficacious for contraception and hormone replacement therapy, and have high patient compliance, are now in development for ART. However, developing effective IVRs to deliver progesterone beyond 7 days is challenging due to limitations of current engineering processes, and difficulty in controlling release rates, thus mandating drug-specific customized IVR designs. Our goal is to address these limitations by revolutionizing the engineering and manufacturing processes for intravaginal rings, using a state-of-the-art 3D printing process known as continuous liquid interface production (CLIP™). Using the automated CLIP process, we can engineer and manufacture IVRs with surface geometries not achievable with traditional injection molding or extrusion, which help control drug release. CLIP enables us to precisely fine-tune diffusion and release of drugs, to achieve near complete release, and independently control IVR mechanical properties. Importantly, using CLIP, we can manufacture IVRs that provide sustained release of progesterone to cover the entire ART treatment period in a rapid and cost-effective single-step process. In this Phase II SBIR project, we propose to build on our existing data from Phase I to optimize a progesterone IVR named AnelleO-PRO, test its efficacy in a relevant macaque model, and conduct IND-enabling studies to support an IND-application. We will implement comprehensive rational IVR design, using the highly relevant preclinical sheep and macaque models to characterize the safety, pharmacokinetic profiles, and efficacy of optimized AnelleO-PRO. This multidisciplinary, cutting-edge approach will develop a unique and highly innovative 3D printed CLIP IVR – AnelleO-PRO, delivering progesterone in a long-acting, single administration treatment of infertility.

项目概要不孕不育是一个全球性的健康问题，仅在美国，每年就有约 170 万名女性接受不孕不育治疗。改善不孕症治疗，迫切需要推广对患者友好的黄体酮方法辅助生殖技术（ART）的补充，阴道环具有良好的耐受性。女性，对避孕和激素替代疗法有效，并且患者依从性高，目前正在开发 ART 然而，开发有效的 IVR 来提供 7 天以上的黄体酮是很困难的。由于当前工程工艺的限制以及难以控制释放速率，因此具有挑战性我们的目标是通过彻底改变药物特定的定制 IVR 设计来解决这些限制。使用最先进的 3D 打印工艺进行阴道环的工程和制造工艺称为连续液体界面生产 (CLIP™) 使用自动化 CLIP 流程，我们可以进行设计。并制造具有传统注塑或挤压无法实现的表面几何形状的 IVR，这有助于控制药物释放，使我们能够精确调整药物的扩散和释放，以实现接近完全释放，并独立控制 IVR 机械性能重要的是，使用 CLIP，我们可以。制造可持续释放黄体酮的 IVR，以覆盖整个 ART 治疗期在这个第二阶段 SBIR 项目中，我们建议以我们现有的方式为基础。来自第一阶段的数据，用于优化名为 AnelleO-PRO 的黄体酮 IVR，并在相关猕猴中测试其功效模型，并进行 IND 支持研究以支持 IND 申请。合理的IVR设计，利用高度相关的临床前绵羊和猕猴模型来表征安全性，优化的 AnelleO-PRO 的药代动力学特征和功效。这种多学科的尖端方法。将开发独特且高度创新的 3D 打印 CLIP IVR – AnelleO-PRO，在长效、单次给药治疗不孕症。