Next Generation Multipurpose Intravaginal Ring Technology Using Innovative CLIP 3D Printing

项目摘要 在全球范围内，50%以上的艾滋病毒感染者是妇女，每年约50%的怀孕是意外怀孕。 因此，迫切需要促进由女性控制的多用途预防和分娩方法 可以与性行为分离的策略。女性对阴道环的耐受性良好， 有效用于避孕和激素替代疗法，并具有高患者可接受性， 合规1-4。然而，由于目前的限制，开发有效的多用途IVR具有挑战性。 工程过程5-6，以及药物性质和释放速率的差异，因此要求药物特异性 定制的IVR设计。我们的目标是通过彻底改变 阴道环使用最先进的3D打印工艺，称为连续液体界面生产 (CLIP™）7.使用CLIP，我们可以设计具有复杂几何形状的IVR，这是传统的 注射成型或挤出成型。环内复杂的几何形状将使我们能够精确地微调扩散 和药物从IVR释放，并实现药物从IVR的几乎完全释放。更重要的是， 有了CLIP，我们可以制造多用途的IVRs，它可以整合2种或更多种药物， 意外怀孕和性传播感染（艾滋病毒，HSV-2，HPV）在一个快速和具有成本效益的单步过程。在这 NGM R 01赠款和我们现有的数据的基础上，我们提出了一个全面的评估这一创新 使用高度相关的动物模型作为宝贵的临床前工具来评估安全性和 3D CLIP MPT的药代动力学特征。将利用这一尖端组合方法来评估 我们建议在绵羊和猕猴中研究一种独特的， 高度创新的3D打印多用途IVR技术。

PROJECT SUMMARY Globally, over 50% of those infected with HIV are women, and annually, ~50% of all pregnancies are unintended. Therefore, there is a critical need to promote female-controlled methods of multipurpose prevention and delivery strategies that can be disassociated from the sex act. Intravaginal rings are well tolerated by women, are efficacious for contraception and hormone replacement therapy, and have high patient acceptability and compliance 1-4. However, developing effective multipurpose IVRs is challenging due to the limitations of current engineering processes 5-6, and differences in drug properties and release rates, thus mandating drug-specific customized IVR designs. Our goal is to address these limitations by revolutionizing the engineering process of intravaginal rings using a state-of-the-art 3D printing process known as the continuous liquid interface production (CLIP™)7. Using CLIP, we can engineer IVRs with complex geometries that cannot be achieved with traditional injection molding or extrusion. The complex geometries within the ring will allow us to precisely fine-tune diffusion and release of drugs from the IVR, and achieve near complete release of drugs from the IVR. More importantly, with CLIP, we can manufacture multipurpose IVRs that can integrate 2 or more drugs to prevent against unintended pregnancies and STIs (HIV, HSV-2, HPV) in a rapid and cost effective single-step process. In this NGM R01 grant and building on our existing data, we propose a comprehensive evaluation of this innovative approach using highly relevant animal models as invaluable preclinical tools to assess the safety and pharmacokinetic profiles of 3D CLIP MPT. This cutting edge combined approach will be utilized to evaluate the scientific premise of our proposal in sheep and macaques to investigate the safety and efficacy of a unique and highly innovative 3D printed multipurpose IVR technology.