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：
10063935
负责人：
Soumya Rahima Benhabbour
金额：
$ 76.6万
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/10063935
关键词：
3-Dimensional 3D Print AIDS prevention Address Adherence Affinity Anatomy Animal Model Anti-Retroviral Agents Antiviral Agents Behavioral Biological Cervical Characteristics Complex Contraceptive Agents Contraceptive methods Custom 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 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 TMC120-R147681 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.

项目摘要在全球范围内，超过50％的感染艾滋病毒的人是女性，每年约有50％的怀孕是意想不到的。因此，迫切需要促进女性控制的预防和交付方法可以与性行为分离的策略。静脉内环由女性容忍，是有效的避孕和替代疗法，患者的可接受性高，并且合规性1-4。但是，由于当前的局限工程过程5-6，药物特性和释放率的差异，因此强制性药物特异性定制的IVR设计。我们的目标是通过彻底改变使用最先进的3D打印过程称为连续液体界面生产（clip™）7。使用剪辑，我们可以用传统的几何形状来设计IVRS的复杂几何形状注入成型或延伸。环内的复杂几何形状将使我们能够精确微调扩散并从IVR中释放药物，并几乎完全从IVR释放药物。更重要的是，使用剪辑，我们可以生产可以整合2种或更多药物以防止的多功能IVR 意外怀孕和性传播疾病（HIV，HSV-2，HPV）在快速且具有成本效益的单步过程中。在这个 NGM R01赠款并基于我们现有数据，我们提出了对这一创新性的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，以评估安全性和 3D夹MPT的药代动力学轮廓。这种尖端组合方法将用于评估我们对绵羊和猕猴提出的科学信念，以调查独特和效率的安全性和效率高度创新的3D印刷多功能IVR技术。