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

采用创新 CLIP 3D 打印的下一代多用途阴道环技术

基本信息

批准号：
10308467
负责人：
Soumya Rahima Benhabbour
金额：
$ 77.44万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-12-01 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10308467
关键词：
3-Dimensional 3D Print AIDS prevention Address Adherence Affinity Anatomy Animal Model Anti-Retroviral Agents Behavioral Biological Cervical Characteristics Complex Contraceptive Agents Contraceptive methods Custom Dapivirine Data Development Development Plans Device Designs Device Removal Devices Diffusion Drug Delivery Systems Drug Design Drug Kinetics Effectiveness Engineering Epidemic Epidemiology Etonogestrel Evaluation Excision Female Formulation Fostering Geometry Goals Grant HIV HIV/STD Health Benefit Histology Hormone replacement therapy Human Herpesvirus 2 Human Papillomavirus In Vitro Infection Injections Lead Link Liquid substance Macaca Measures Methodology Methods Molds Patients Pattern Perception Performance Permeability Persons Pharmaceutical Preparations Pharmacodynamics Pharmacology Physiology Plasma Population Heterogeneity Prevention Process Production Property Prophylactic treatment Public Health Recording of previous events Regimen Safety Sensory Sheep Steroids Surface Properties Tail Technology Testing Time Tissues User Compliance Vagina Vaginal Ring Woman controlled release cost effective design drug release kinetics efficacy evaluation experience high risk implementation design in vitro Assay in vivo innovation mechanical properties microbicide multidisciplinary next generation nonhuman primate older women pharmacodynamic model pre-clinical preference prevent prophylactic prototype quality assurance sex simian human immunodeficiency virus sound success tool transmission process unintended pregnancy vaginal microbiome willingness young woman

项目摘要

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.

项目概要在全球范围内，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，迫切需要推广女性控制的多用途预防和分娩方法女性可以很好地耐受与性行为无关的策略。对避孕和激素替代治疗有效，患者接受度高合规性 1-4. 然而，由于当前的限制，开发有效的多功能 IVR 具有挑战性。工程流程 5-6，以及药物特性和释放速率的差异，从而要求针对特定药物我们的目标是通过彻底改变 IVR 的工程流程来解决这些限制。使用最先进的 3D 打印工艺（称为连续液体界面生产）制造阴道环 (CLIP™)7. 使用 CLIP，我们可以设计具有传统无法实现的复杂几何形状的 IVR。注塑或挤压环内的复杂几何形状将使我们能够精确地微调扩散。并从IVR中释放药物，并实现药物从IVR中接近完全的释放。通过 CLIP，我们可以制造多用途 IVR，可以集成 2 种或多种药物来预防通过快速且经济有效的单步过程来预防意外怀孕和性传播感染（HIV、HSV-2、HPV）。 NGM R01 资助并根据我们现有的数据，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 3D CLIP MPT 的药代动力学特征将利用这种尖端的组合方法来评估我们在绵羊和猕猴身上研究一种独特且有效的药物的安全性和有效性的建议的科学前提高度创新的 3D 打印多用途 IVR 技术。