A Nanotherapeutic Device for Effective Non-Surgical Female Sterilization

用于有效非手术女性绝育的纳米治疗装置

基本信息

批准号：
9284285
负责人：
Ulrike Gesa Katharina Wegst
金额：
$ 23.78万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-03 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9284285
关键词：
Ablation Address Aftercare Animal Model Area Cervix Uteri Cicatrix Contraceptive Agents Contrast Media Development Device Removal Devices Diffusion Disadvantaged Dose Ectopic Pregnancy Embryo Transfer Endometrial Family Felidae Felis catus Female Sterilization Fertilization in Vitro Fiber Fibrosis Foreign Bodies Frequencies Future Gel General Anesthesia Germany Goals Greater sac of peritoneum Healthcare Heating Horns Human Hypersensitivity Hysterosalpingography Hysteroscopes Immobilization Implant In Situ In Vitro Inflammation Investigation Magnetic nanoparticles Mammalian Oviducts Metals Methods Modeling Morbidity - disease rate Mucous Membrane Operative Surgical Procedures Organ Outpatients Paste substance Perforation Performance Pharmacologic Substance Polymers Pregnant Women Procedures Property Risk Safety Silicones Site Speed Spontaneous abortion Sterilization Surgical incisions System Techniques Technology Temperature Testing Tissues Tubal Ligation Tubal Occlusion Tube United States Food and Drug Administration Uterus Vagina Viscosity Withdrawal Woman base birth control comparative efficacy cost cost effective design efficacy testing experience flexibility implantation improved in vivo innovation magnetic field manufacturing process migration nanotherapeutic novel particle public health relevance reproductive tissue phantom tumor

项目摘要

DESCRIPTION (provided by applicant): The Essure system is one type of effective, permanent birth control for women that relies on the insertion of a polymer-coated metal or fiber coil into the Fallopian tube to cause inflammation and through it their irreversible blockage with scar tissue. Advantages over tubal ligation are that the insertion of the device through the vagina, the cervix and the uterus into the Fallopian tube with a hysteroscope (a flexible tube equipped with a camera) is an effective (<1% women pregnant during first year after implantation), permanent, low-cost, non-surgical procedure which typically takes less than 30 min. Disadvantages are that Essure takes 3 months to become effective, that allergies to the contrast-agent used in hysterosalpingography to confirm tubal blockage is a contraindication, that electrosurgical procedures (e.g. endometrial ablation) may no longer be possible, and that complications, when they occur, can be very serious, such as ectopic pregnancies, miscarriages and the perforation of the uterus or fallopian tubes by the metal coils and their migration into other organs. Increasing concerns surrounding Essure highlight the need for a new, improved device that offers Essure's advantages without its risks. We propose a novel device that uses precisely dosed, site-specifically delivered magnetic nanoparticles (MNP) and their temporary immobilization in the Fallopian tubes for heating with an externally applied alternating magnetic field (AMF) to cause initial physical blockage, localized heating and inflammation, followed by scar formation and permanent tube blockage. Such a MNP-based device has never been demonstrated. Our preliminary results illustrate the great promise of this approach through: i) the homogeneous distribution of a well-defined concentration of MNPs in a non-penetrating, flexible device for ii) targeted placement and uniform heating during treatment that iii) allows fo the delivery of a well-controlled heat dose and, after treatment, iv) removes itself by controlled degradation v) whose components have been proven not to be toxic, vi) has shown tubal occlusion in only thirty days in an animal model, and vii) which will not preclude in vitro fertilization by the presence of a foreign body in the uterus. For the study of the proposed MNP-enabled device, we will use NT-01 particles (Micromod GmbH, Rostock, Germany) that have been manufactured by the Good Manufacturing Process (GMP) are currently under review for approval by the U.S. Food and Drug Administration for human use. We will determine the optimal material composition and consistency (e.g. gel, paste) for MNP delivery, device heating and degradation. While we propose the use of a specific type of MNP for this study, because of considerable experience with them, the device will be particle independent; in fact, we anticipate that further studies beyond the scope of this one will show that the combination of several different MNP types with different heating and diffusion properties may be advantageous. Key to the proposed approach is the hypothesis that MNP can be carefully dosed and site-specifically placed for sterilization and then safely be removed by device degradation. The hypotheses will be addressed in three interrelated aims. In Aim 1, we will develop a MNP-based device with well-defined heating properties for placement into the Fallopian tube with a hysteroscope. In Aim 2, we will in in vitro studies systematically determine the heating performance of different device options developed in Aim 1. Finally, in Aim 3 we will systematically test in vivo in cats th efficacy of the device. The successful completion of the project will be transformative to the field, offering new, low cost sterilization options, with all of Essure's advantages and significanly reduced risks.

描述（由适用提供）：Essure系统是一种有效的，永久性的避孕措施，用于依赖于将聚合物涂层的金属或纤维线圈插入输卵管，以引起炎症，并通过其不可逆的疤痕组织引起炎症。优于管子结扎的优势是，通过阴道，子宫颈和子宫插入带有宫腔镜（与摄像机等效的柔性管）的输卵管中的插入是有效的（植入后第一年怀孕的1％女性），永久性，低成本的，低成本的，非表面性的手术少于30分钟。 Disadvantages are that Essure takes 3 months to become effective, that allergies to the contrast-agent used in hysterosalpingography to confirm tubal blockage is a contraindication, that electrosurgical procedures (e.g. endometrial ablation) may no longer be possible, and that complications, when They occur, can be very serious, such as ecopic pregnancy, miscarriages and the perforation of the uterus or fallopian tubes通过金属线圈及其迁移到其他器官。越来越多的涉及Essure的担忧强调了对新的，改进的设备的需求，该设备提供了Essure的优势而没有其风险。我们提出了一种新型设备，该设备使用精确服用的位点特异性磁性纳米颗粒（MNP）及其在输卵管中的临时固定化，并使用外部施加的替代磁场（AMF）进行加热，以引起初始物理阻塞，局部加热，局部加热和入射，然后进行疤痕形成和永久性管封闭。这种基于MNP的设备从未被证明。 Our preliminary results illustrate the great promise of this approach through: i) the homogeneous distribution of a well-defined concentration of MNPs in a non-penetrating, flexible device for ii) targeted placement and uniform heating during treatment that iii) allows fo the delivery of a well-controlled heat dose and, after treatment, iv) removes itself by controlled degradation v) whose components have been proven not to be toxic, vi）在动物模型中仅在三十天内显示了输卵管阻塞，而VII）并不能阻止子宫中异物的存在在体外受精。为了研究拟议的以MNP为基础的设备，我们将使用良好的制造过程（GMP）制造的NT-01颗粒（Micromod GmbH，Rostock，德国），目前正在接受美国食品和药物管理局的批准。我们将确定用于MNP输送，设备加热和降解的最佳材料组成和一致性（例如凝胶，糊状）。尽管我们建议使用特定类型的MNP进行本研究，但由于对其进行了考虑，该设备将独立于粒子。实际上，我们预计，超出该范围的进一步研究将表明，几种不同的MNP类型具有不同的加热和差异性能的组合可能是有利的。提出的方法的关键是假设可以仔细给予MNP并特异性地放置进行灭菌，然后通过设备降解安全去除。这些假设将以三个相互关联的目的来解决。在AIM 1中，我们将开发一个具有明确定义的加热特性的基于MNP的设备，以使用宫腔镜放置在输卵管中。在AIM 2中，我们将体外研究系统地确定AIM 1中开发的不同设备选项的加热性能。最后，在AIM 3中，我们将在猫中系统地在体内测试该设备的有效性。该项目的成功完成将对该领域进行变革，提供新的低成本灭菌选择，并具有所有优势，并大大降低了风险。