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

创新的 3D 打印阴道环：重新设计多用途阴道环，用于预防艾滋病毒、性传播感染和意外怀孕

• 批准号: 9761451
• 负责人: Soumya Rahima Benhabbour
• 金额: $ 45.58万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-08 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9761451
• 关键词: 3-Dimensional; 3D Print; AIDS prevention; Address; Animal Model; Anti-Retroviral Agents; Complex; Contraceptive Agents; Contraceptive methods; Custom; Development; Diffusion; Drug Delivery Systems; Drug Kinetics; Drug usage; Engineering; Epidemic; Ethics; Evaluation; Female; Formulation; Geometry; Goals; HIV; HIV Infections; Hormone replacement therapy; Human; Human Herpesvirus 2; Human Papillomavirus; In Vitro; Inbred BALB C Mice; Infection; Injections; Liquid substance; Local Microbicides; Low income; Macaca; Macaca nemestrina; Measures; Methods; Modeling; Molds; Mucous Membrane; Pharmaceutical Preparations; Pharmacology; Phase; Placebos; Plant Resins; Plasma; Pre-Clinical Model; Prevention; Prevention approach; Preventive Intervention; Printing; Process; Production; Property; Prophylactic treatment; Regimen; Reproductive Health; Research; Route; SIV; Safety; Sexually Transmitted Diseases; Simplexvirus; Technology; Tissues; Unsafe Sex; Vagina; Vaginal Douching; Vaginal Ring; Virus; Woman; biomaterial compatibility; cervicovaginal; compliance behavior; cost effective; cytotoxicity; design; drug release kinetics; efficacy evaluation; experimental study; high risk; human subject; improved; in vivo; in vivo evaluation; innovation; nonhuman primate; pre-clinical; pre-exposure prophylaxis; preclinical efficacy; prevent; prophylactic; rectal; safety assessment; screening; sex; simian human immunodeficiency virus; targeted treatment; technique development; tool; transmission process; trial design; unintended pregnancy

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.

摘要： 在全球范围内，50%以上的艾滋病毒感染者是妇女，每年约有50%的孕妇是 无意的。因此，迫切需要促进由女性控制的多用途避孕方法。 可以与性行为无关的预防和实施策略。阴道环 女性耐受，可有效用于避孕和激素替代疗法， 患者依从性[1-4]。然而，由于复杂性，开发有效的多用途IVRs具有挑战性 目前的工程工艺[5，6]，以及药物性质和释放速率的差异，因此要求 药物特定的定制IVR设计。本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打印过程来革命性地改变阴道内环的工程过程， 作为连续液体界面生产（CLIP™）[7]。使用CLIP，我们可以设计具有复杂 这是传统注塑或挤出无法实现的几何形状。几何结构比较复杂 环内将使我们能够精确地微调药物从IVR的扩散和释放， 药物从IVR中完全释放。更重要的是，有了CLIP，我们可以制造多用途的IVRs， 可以整合2种或多种药物，以预防意外怀孕和性传播感染（HIV，HSV-2，HPV）， 一种快速且成本有效的单步方法。我们建议全面评估这一创新 使用粘膜猿猴/人类免疫缺陷病毒的高度相关猕猴模型的方法 （SHIV 162 p3）作为一种宝贵的临床前工具，用于评估IVR对SHIV感染的有效性[8- 10]。这种尖端的综合方法将被用来评估我们的建议的科学前提， 调查在持续提供服务的同时，是否可以沿着持续预防艾滋病毒感染 使用独特且高度创新的3D打印多用途IVR的避孕药。