Hollow Fiber Catheter for Drug Delivery into the Prostate

用于将药物输送到前列腺的中空纤维导管

• 批准号: 7803534
• 负责人: Jim Stice
• 金额: $ 39.74万
• 依托单位: TWIN STAR MEDICAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7803534
• 关键词: Animal Model; Antibiotics; Area; Benign Prostatic Hypertrophy; Biological Assay; Bladder; Brain; Brain Neoplasms; Caliber; Canis familiaris; Caring; Cartoons; Catheters; Cisplatin; Clinical; Complication; Contrast Media; Convection; Data; Drug Delivery Systems; Dyes; Economics; Evaluation; Excision; FDA approved; Fiber; Fluoroscopy; Gel; Gene Transfer; Goals; Histocompatibility Testing; Human; Image; Imagery; In Vitro; Infusion procedures; Injection of therapeutic agent; Institutes; Lead; Left; Liquid substance; Lobe; Malignant neoplasm of prostate; Measures; Medical; Methods; Modeling; Morbidity - disease rate; Multicenter Trials; Needles; Operative Surgical Procedures; Pathway interactions; Patient Care; Patients; Pharmaceutical Preparations; Phase; Preclinical Testing; Preparation; Procedures; Property; Prostate; Prostate Ablation; Prostatic Diseases; Reflux; Relative (related person); Research Personnel; Research Proposals; Resources; Risk; Rodent Model; Small Business Innovation Research Grant; Solutions; Stroke; Surface; Technology; Testing; Time; Tissues; Tracer; Twin Multiple Birth; Validation; Work; aging population; body system; clinical efficacy; clinically relevant; commercialization; design; drug distribution; experience; improved; in vivo; men; minimally invasive; nervous system disorder; novel; pre-clinical; public health relevance; success; tissue phantom

DESCRIPTION (provided by applicant): Significance: Benign Prostatic Hyperplasia (BPH) will become an increasing burden on economic resources with the aging population. Surgical treatment is well established and has provided satisfactory results in 60 - 80% of men. However, it has been associated with significant morbidity and risk of complications; therefore considerable efforts have been directed toward developing alternative minimally invasive treatments. Ablation of the prostate by direct injection has the potential to significantly reduce expense and morbidity; drugs are available to chemically ablate the tissue. However, though direct injection is a seemingly straightforward approach to the problem, backflow along the needle track and uneven distribution of drug after injection are significant drawbacks to chemoablation. In contrast to conventional injection needles, the hollow fiber delivery catheter is completely porous; therefore the surface area of tissue in contact with infusate is considerably increased. Hypothesis: We hypothesize that use of a hollow fiber catheter for direct infusion into the prostate will result in elimination of backflow and greater volume of distribution than the standard-of-care needle injection. Preliminary Data: We have demonstrated that the hollow fiber eliminates shear plane and reflux in a tissue phantom gel model, and increases the amount of adenoviral gene transfer by ten times in rodent models (relative to needle infusion). Specific Aims: This project entails preclinical testing of the hollow fiber catheter for eventual application to human patients with prostate disorders. In Specific Aim 1, we will construct and validate human-scale hollow fiber catheters that are suitable for use in dogs. A widely used clinical injection needle will be directly compared to hollow fiber for delivery of dye in a gel model and ex vivo dog prostates. Reflux of infusate and delivery distribution will be quantified along with catheter transmittance properties. In Specific Aim 2, we will use the validated catheters and compare to needles with in vivo injections into a dog prostate. An antibiotic, dye, and contrast solution will be infused and distribution will be determined by evaluation of reflux into bladder by assay (antibiotic), reflux along needle track by fluoroscopy (contrast) and prostate distribution by dye visualization (post procedure prostate removal and sections). Together, these studies will demonstrate the utility of hollow fiber catheters for prostate injections and accelerate the commercialization of hollow fiber for clinical use. PUBLIC HEALTH RELEVANCE: Drug delivery into the prostate represents a significant obstacle to achieving clinical efficacy. We have developed a novel "hollow fiber" catheter and shown its potential with preliminary studies as a direct injection method for the prostate. In this project, we will conduct preclinical feasibility testing of the hollow fiber catheter in dog prostates in preparation for clinical use of this technology in human patients.

描述（由申请人提供）：意义：随着人口老龄化，良性前列腺增生（BPH）将成为经济资源日益增加的负担。手术治疗是公认的，并提供了令人满意的结果，在60 - 80%的男性。然而，它已与显着的发病率和并发症的风险，因此，相当大的努力已经指向开发替代微创治疗。通过直接注射消融前列腺有可能显著降低费用和发病率;药物可用于化学消融组织。然而，尽管直接注射是解决该问题的一种看似简单的方法，但沿着针道的回流和注射后药物的不均匀分布是化学消融的显著缺点。与传统的注射针相比，中空纤维输送导管是完全多孔的;因此，与输注液接触的组织的表面积显著增加。假设：我们假设使用中空纤维导管直接输注到前列腺中将导致消除回流和比标准护理针注射更大的分布容积。初步数据：我们已经证明，中空纤维消除了剪切平面和组织模型凝胶模型中的回流，并增加了腺病毒基因转移的啮齿动物模型中的量的十倍（相对于针输注）。具体目标：该项目需要对中空纤维导管进行临床前测试，以最终应用于前列腺疾病患者。在特定目标1中，我们将构建并验证适用于犬的人体规模中空纤维导管。将广泛使用的临床注射针直接与中空纤维进行比较，用于在凝胶模型和离体犬前列腺中递送染料。将沿着导管透射率特性量化输注液回流和输送分布。在特定目标2中，我们将使用经确认的导管，并与体内注射到犬前列腺中的针头进行比较。将输注抗生素、染料和造影剂溶液，并通过测定（抗生素）评价反流进入膀胱、通过荧光透视（造影剂）评价沿针道反流以及通过染料可视化（术后前列腺切除和切片）评价前列腺分布来确定分布。总之，这些研究将证明中空纤维导管用于前列腺注射的实用性，并加速中空纤维临床应用的商业化。 公共卫生相关性：药物输送到前列腺是实现临床疗效的一个重大障碍。我们开发了一种新型的“中空纤维”导管，并通过初步研究显示了其作为前列腺直接注射方法的潜力。在本项目中，我们将在犬前列腺中进行中空纤维导管的临床前可行性测试，为该技术在人类患者中的临床应用做准备。

项目成果

A pilot study in intraparenchymal therapy delivery in the prostate: a comparison of delivery with a porous needle vs standard needle.

前列腺实质内治疗递送的初步研究：多孔针与标准针递送的比较。

• DOI: 10.1186/s12894-018-0378-8
• 发表时间: 2018
• 期刊: BMC urology
• 影响因子: 2
• 作者: Brady,MartinL;Coffield,KingScott;Kuehl,ThomasJ;Raghavan,Raghu;SpeightsJr,VO;Patel,Belur;Wilson,Scott;Wilson,Mike;Odland,RickM
• 通讯作者: Odland,RickM