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

项目总结 不孕不育是一个全球性的健康问题。仅在美国，每年就有约170万女性因不孕不育接受治疗。至 改善不孕症的治疗，迫切需要推广对患者友好的黄体酮治疗方法 辅助生殖技术(ART)的补充。阴道内环，这是耐受性良好的 女性，在避孕和激素替代治疗方面有效，患者依从性高， 现在正在为艺术而发展。然而，开发有效的静脉注射受体来提供超过7天的黄体酮是 由于当前工程工艺的限制以及难以控制发布速度，因此具有挑战性 强制要求针对特定药物的定制IVR设计。我们的目标是通过使 使用最先进的3D打印工艺的阴道内环的工程和制造工艺 称为连续液体界面生产(CLIP™)。使用自动剪裁过程，我们可以设计 并制造具有传统注射成型或挤出不能实现的表面几何形状的IVR， 这有助于控制药物的释放。CLIP使我们能够精确微调药物的扩散和释放，以实现 接近完全释放，并独立控制IVR的机械性能。重要的是，使用CLIP，我们可以 制造IVR，提供黄体酮的持续释放，以覆盖整个ART治疗期 快速且经济实惠的单步工艺。在这个第二期SBIR项目中，我们建议在现有的基础上 来自第一阶段的数据优化了名为AnelleO-PRO的黄体酮IVR，在相关的猕猴身上测试了它的有效性 模型，并进行支持IND的研究，以支持IND应用。我们将全面实施 合理的IVR设计，使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疗效。这种多学科、尖端的方法 将开发一种独特且高度创新的3D打印剪辑IVR-AnelleO-PRO，在 长效、单次给药治疗不孕不育。

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.