Innovative 3D Printed Intravaginal Rings: Reengineering Multipurpose Intravaginal Rings for Prevention of HIV, STIs and Unintended Pregnancy

摘要： 在全球范围内，超过50%的艾滋病毒感染者是女性，每年约50%的孕妇是 不是故意的。因此，迫切需要促进控制妇女的多用途方法。 可与性行为分离的预防和交付策略。阴道内环很好 女性耐受，对避孕和激素替代治疗有效，并有很高的 患者依从性[1-4]。然而，由于IVR的复杂性，开发有效的多功能IVR是具有挑战性的 目前的工程工艺[5，6]，以及药物特性和释放速率的差异，因此要求 针对特定药物的定制IVR设计。该提案的最终目标是通过以下方式解决这些限制 使用已知的最先进的3D打印工艺革新阴道内环的工程工艺 作为连续的液体界面生产(CLIP™)[7]。使用CLIP，我们可以设计复杂的IVR 传统注塑或挤出无法实现的几何形状。复杂的几何图形 环内将允许我们精确微调药物从IVR的扩散和释放，并实现接近 从IVR中完全释放药物。更重要的是，有了CLIP，我们就可以制造多用途的IVR 可以整合2种或更多药物来预防意外怀孕和性传播感染(HIV、HSV-2、HPV) 一种快速且经济高效的单步流程。我们建议对这一创新进行全面评估 使用高度相关的猴/人类免疫缺陷病毒黏膜模型的方法 (SHIV162p3)作为评估静脉注射受体对抗SIV获得的有效性的宝贵的临床前工具[8- 10]。这一先进的综合方法将被用来评估我们提议的 调查是否可以在持续提供服务的同时实现对艾滋病毒感染的持续预防 使用独特和高度创新的3D打印多用途IVR的避孕药。

Abstract: 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 compliance [1-4]. However, developing effective multipurpose IVRs is challenging due to the complexity of current engineering processes [5, 6], and differences in drug properties and release rates, thus mandating drug-specific customized IVR designs. The ultimate goal of this proposal 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. We propose a comprehensive evaluation of this innovative approach using a highly relevant macaque model of mucosal simian/human immunodeficiency virus (SHIV162p3) as an invaluable preclinical tool to assess the efficacy of the IVRs against SHIV acquisition [8- 10]. This cutting edge combined approach will be utilized to evaluate the scientific premise of our proposal to investigate whether sustained protection against HIV acquisition can be achieved along with sustained delivery of a contraceptive drug using a unique and highly innovative 3D printed multipurpose IVR.