SBIR-STTR Award

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.

Thesaurus Terms:
(Sp-4-2)-Diamminedichloroplatinum; Abscission; Animal Model; Animal Models And Related Studies; Antibiotic Agents; Antibiotic Drugs; Antibiotics; Apoplexy; Area; Assay; Benign Prostatic Hypertrophy; Bioassay; Biologic Assays; Biological Assay; Bladder; Body Tissues; Brain; Brain Neoplasia; Brain Neoplasms; Brain Tumors; Cddp; Caliber; Cancer Of Prostate; Canine Species; Canis Familiaris; Caring; Cartoons; Catheters; Cerebral Stroke; Cerebrovascular Apoplexy; Cerebrovascular Stroke; Cerebrovascular Accident; Cis-Diammine-Dichloroplatinum; Cis-Diamminedichloridoplatinum; Cis-Diamminedichloro Platinum (Ii); Cis-Dichloroammine Platinum (Ii); Cis-Platinous Diamine Dichloride; Cis-Platinum Ii; Cis-Platinum Ii Diamine Dichloride; Cisplatin; Cisplatina; Cisplatinum; Clinical; Coloring Agents; Complication; Contrast Agent; Contrast Drugs; Contrast Media; Convection; Crossmatching, Tissue; Cysplatyna; Ddp; Data; Diameter; Dichlorodiammineplatinum; Dogs; Drug Delivery; Drug Delivery Systems; Drug Targeting; Drug Targetings; Drugs; Dyes; Economics; Encephalon; Encephalons; Evaluation; Excision; Extirpation; Fda Approved; Fiber; Fluoroscopy; Gel; Gene Transfer; Genital System, Male, Prostate; Goals; Histocompatibility Testing; Human; Human Prostate; Human Prostate Gland; Human, General; Image; Imagery; In Vitro; Infusion; Infusion Procedures; Injection Of Therapeutic Agent; Injections; Institutes; Investigators; Lead; Left; Liquid Substance; Lobe; Malignant Tumor Of The Prostate; Malignant Neoplasm Of Prostate; Malignant Prostatic Tumor; Mammals, Dogs; Man (Taxonomy); Man, Modern; Measures; Medical; Medication; Methods; Miscellaneous Antibiotic; Modeling; Morbidity; Morbidity - Disease Rate; Multicenter Trials; Needles; Nervous System Diseases; Nervous System, Brain; Neurologic Disorders; Neurological Disorders; Operation; Operative Procedures; Operative Surgical Procedures; Organ System; Pathway Interactions; Patient Care; Patient Care Delivery; Patients; Pb Element; Peyrone's Chloride; Peyrone's Salt; Pharmaceutic Preparations; Pharmaceutical Preparations; Phase; Platinum Diamminodichloride; Platinum, Diaminedichloro-, Cis- (8ci); Platinum, Diamminedichloro-, (Sp-4-2)-; Preclinical Testing; Preparation; Procedures; Property; Property, Loinc Axis 2; Prostate; Prostate Ablation; Prostate Ca; Prostate Cancer; Prostate Disease; Prostate Gland; Prostatic Cancer; Prostatic Diseases; Prostatic Gland; Prostatic Hyperplasia, Benign; Prostatic Hypertrophy, Benign; Radiopaque Media; Reflux; Relative; Relative (Related Person); Removal; Research Personnel; Research Proposals; Research Resources; Researchers; Resources; Risk; Rodent Model; Sbir; Sbirs (R43/44); Small Business Innovation Research; Small Business Innovation Research Grant; Solutions; Stroke; Surface; Surgical; Surgical Interventions; Surgical Procedure; Surgical Removal; Tag; Technology; Testing; Time; Tissue Crossmatchings; Tissue Typing; Tissues; Tracer; Twin Multiple Birth; Twins; Urinary System, Bladder; Validation; Vascular Accident, Brain; Visualization; Work; Aging Population; Benign Prostate Hyperplasia; Body System; Brain Attack; Canine; Cerebral Vascular Accident; Cis Dichlorodiammineplatinum; Cis Platinum Compound; Cis-Diaminedichloroplatinum; Cis-Diamminedichloroplatinum; Cis-Diamminedichloroplatinum(Ii); Cis-Dichlorodiammineplatinum(Ii); Cis-Platinum; Clinical Efficacy; Clinical Relevance; Clinically Relevant; Commercialization; Design; Designing; Domestic Dog; Drug Distribution; Drug/Agent; Experience; Fluid; Heavy Metal Pb; Heavy Metal Lead; Histocompatibility Typing; Imaging; Improved; In Vivo; Liquid; Men; Men's; Minimally Invasive; Model Organism; Nervous System Disorder; Neurological Disease; Novel; Pathway; Pre-Clinical; Preclinical; Prostate Disorder; Public Health Relevance; Resection; Stroke; Success; Surgery; Tissue Phantom; Transfer Of A Gene; Tumors In The Brain; Urinary Bladder

The significance of the proposed research is based on the growing demand for healthcare resources to treat and manage prostatic disease, particularly benign prostatic hyperplasia (BPH) and cancer. Both the incidence and cost of treatment for BPH, and its complications, are growing rapidly with the aging U.S. population; prostate cancer is the second-leading cause of cancer deaths among men in the U.S. There is a clear need for minimally invasive, cost-effective therapies to match the outcomes of surgical treatment options, which are associated with significant morbidity and complications. Prostate injections have not become standard of care due to inadequate drug distribution with needles. The Applicants have developed a microporous hollow fiber catheter (MiHFC) for improved injection distribution in the prostate. Phase II innovations focus on further developing MiHFC and combining existing treatment planning methods for drug delivery injections into human prostates with the objective to develop a system that is ready for human clinical use. The same MiHFC device with small changes would be adaptable for use in many other human clinical applications needing improved injection systems, such as liver, kidney and other solid organs. This would allow researchers to use MiHFC devices for other research projects involving human drug injections, either with or without treatment planning. Hypothesis: The MiHFC injection system being developed in Phase II will give urologists and researchers a more reliable tool to plan and deliver injection therapies into the human prostate. Preliminary Data: In Phase I research, the innovative use of applicant's MiHFC to improve injection drug delivery into the prostate was successful with MiHFC significantly improving ethanol distribution in canine prostates as compared to needle injections. Specific Aims: The objective of this Phase II proposal is to further develop the applicant's innovative drug delivery system for improved prostate disease therapies and to provide the bench and animal study data to accelerate its clinical use. Aim 1: Finalize human use MiHFC design. The Phase I MiHFC design will be optimized to meet human use specifications established from user requirements. Aim 2: Infusion studies and analysis. Human ex vivo and baboon in vivo studies will be conducted to assess MiHFC safety and agent distribution and to develop of a prostate specific treatment planning system. Aim 3: Design verification and 510(k) submission. Design verification test data and FDA 510(k) clearance will facilitate clinical adoption and commercialization.

Public Health Relevance Statement:


Public Health Relevance:
There is a significant demand for healthcare resources to treat and manage prostate diseases. The objective of this Phase II proposal is to develop an innovative drug delivery system for improved prostate disease therapies and to provide the bench and animal study data to accelerate its clinical use.

Project Terms:
Adoption; Aging; aging population; Animals; Area; base; Benign Prostatic Hypertrophy; Cancer Etiology; Canis familiaris; Catheters; Cessation of life; Clinical; clinical application; clinical practice; commercialization; Computer software; cost effective; Data; design; Development; Devices; Disease; Drug Delivery Systems; drug distribution; Dyes; effective therapy; Ethanol; Evaluation; Fiber; Healthcare; Human; human study; Image; improved; in vivo; Incidence; Infusion procedures; Injection of therapeutic agent; innovation; insight; Kidney; Knowledge; Lead; Light; Liver; Magnetic Resonance; Malignant neoplasm of prostate; Malignant Neoplasms; meetings; men; Methods; Methylene blue; minimally invasive; Modeling; Modification; Morbidity - disease rate; Needles; Operative Surgical Procedures; Oral; Organ; Outcome; Papio; Performance; Pharmaceutical Preparations; Phase; Population; Prostate; Prostatic Diseases; public health relevance; Research; Research Methodology; Research Personnel; Research Project Grants; Resources; Safety; Science; Solid; standard of care; Structure; System; Testing; Therapeutic; Time; tool; Treatment Cost; treatment planning; Urethra; Urologist