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

项目总结 在全球范围内，超过50%的艾滋病毒感染者是女性，每年约有50%的怀孕是意外怀孕。 因此，迫切需要促进妇女控制的多用途预防和分娩方法。 可以从性行为中分离出来的策略。女性对阴道内环的耐受性很好， 对避孕和激素替代治疗有效，患者可接受性和 合规性1-4。然而，由于当前的局限性，开发有效的多功能IVR是具有挑战性的 工程流程5-6，以及药物特性和释放率的差异，从而授权特定的药物 定制的IVR设计。我们的目标是通过革命性的工程流程解决这些限制 阴道内环使用最先进的3D打印工艺，称为连续液体界面生产 (CLIP™)7.使用CLIP，我们可以设计复杂几何形状的IVR，这是传统方法无法实现的 注塑或挤出。环内的复杂几何结构将使我们能够精确地微调扩散 以及从IVR释放药物，并实现从IVR几乎完全释放药物。更重要的是， 有了CLIP，我们可以制造多用途的IVR，可以集成两种或两种以上的药物来预防 意外怀孕和性传播感染(艾滋病毒、单纯疱疹病毒2型、人乳头瘤病毒)在快速和具有成本效益的一步过程中。在这 NGM R01授权并基于我们现有的数据，我们建议对这一创新进行全面评估 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 3DCLIP MPT的药动学研究这一前沿综合方法将被用来评估 科学前提下，我们建议在绵羊和猕猴身上调查一种独特的和有效的 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.