Hydrodynamic method and apparatus for delivering fluids to kidney tissues
Inventors
Assignees
Indiana University Research and Technology Corp • US Department of Veterans Affairs
Publication Number
US-10980985-B2
Publication Date
2021-04-20
Expiration Date
2034-09-02
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Abstract
The invention provides a catheter and control box apparatus and related methods that are useful in delivering liquids, including liquids comprising nucleic acid molecules into cells. In particular, the invention provides a catheter that stabilizes fluid flow within a vein to deliver a volume, pressure charge of saline solution, exogenous compositions, and isolated vectors to kidney cells, using the renal vein as a guide and under hydrodynamic pressure. The catheter and control box apparatus and related methods described herein are useful to research, prognose, ameliorate symptoms of kidney injury, and treat kidney pathologies.
Core Innovation
The invention provides a catheter and control box apparatus and related methods for delivering liquids, including nucleic acid molecules, into cells of the kidney. It uses the renal vein as a guide to administer a fluid volume and pressure charge of saline solution, exogenous compositions, and isolated vectors under hydrodynamic pressure to kidney cells. This method stabilizes fluid flow within the vein for effective delivery.
The problem being solved is the difficulty in achieving efficient gene transfer to kidney cells in live animals, due to the structural and permeability characteristics of kidney vascular beds, which present challenges to nucleic acid molecule delivery. Existing methods have shown varied and limited gene expression, and issues with injury and low reliability. There is a need for an improved approach that enhances distribution, extent, and duration of gene expression while minimizing injury.
The invention addresses these issues by providing an augmented hydrodynamic method involving retrograde pressure delivery of fluid into the kidney via the renal vein with temporary renal blood vessel occlusion. The method enables delivery of various forms of isolated nucleic acid molecules and therapeutic vectors resulting in nucleic acid expression in kidney cells, widespread delivery to renal cortex and medulla, and affects multiple kidney cell types with limited injury. The invention also includes various embodiments of hydrodynamic pressure delivery catheters with stabilizers to dampen vibratory forces during fluid delivery, and a controlled system to maintain efficacious fluid volumes and pressures for gene transfer.
Claims Coverage
The patent includes twelve inventive features spread across independent claims related to a catheter for fluid delivery, a system comprising the catheter and pump, and methods for delivering fluids to the kidney via the renal vein under controlled hydrodynamic pressure.
Catheter with injection lumen, occluding balloon, stabilizer, and pressure sensor
A catheter comprising a body with an injection lumen terminating at an insertion end for fluid delivery, an occluding balloon spaced apart from the insertion end, a stabilizer with a multi-legged inflatable structure configured to dampen vibratory pulsations of the insertion end during fluid delivery, and at least one pressure sensor near the insertion end for measuring pressures and providing feedback.
Inflatable fluid stabilizer with radial expansion
The stabilizer is a fluid inflatable structure with one or more radially extendable and contractible balloons sized to contact the lumen wall, connected via an actuating lumen for inflation and deflation.
Occluding balloon inflation control
The catheter includes an actuating lumen fluidly connected to the occluding balloon to conduct inflation fluid for balloon deployment to occlude the vessel.
Pressure sensor feedback control unit integration
The catheter's pressure sensor communicates with a control unit to measure blood pressure, fluid delivery pressure, and internal kidney pressure, providing feedback for controlling fluid delivery and occlusion.
System comprising catheter, fluid vessel, pump, control unit, and sensors
A fluid delivery system with a catheter featuring an injection lumen, pressure sensor, occluding balloon, and stabilizer; at least one fluid containment vessel in communication with the catheter; one or more pumps controlled by a control unit; and pressure sensors that provide input to the control unit to regulate fluid delivery into the kidney.
Control of fluid delivery using pressure/time curve
The control unit executes control algorithms using pressure/time profiles to regulate delivery pressure and flow through the catheter to maintain efficacious fluid volumes and pressures during infusion.
Stabilizer inflation control via control algorithm
The stabilizer's inflation is controlled via a lumen connected to an inflation fluid source and regulated by a control algorithm to maintain the catheter insertion end centered within the blood vessel lumen during delivery.
Occluding balloon inflation control via control algorithm
The occluding balloon's inflation is similarly controlled to maintain vessel occlusion during delivery as per feedback from pressure sensors and controlled by the system's algorithms.
Method of renal vein fluid delivery with catheter insertion, stabilization, occlusion, pressure measurement, and controlled infusion
A method comprising inserting the catheter into the renal vein, stabilizing the insertion end using the multi-legged inflatable stabilizer, occluding the vein with the occluding balloon, measuring pressures, and delivering fluid through the injection lumen at flow rates sufficient to maintain target internal kidney pressures over selected durations.
Fluid volume and pressure parameters for method
Delivering fluid volumes ranging approximately from 25 ml to 250 ml, producing hydrodynamic pressures between about 5 mm Hg to 140 mm Hg or causing pressure increases relative to baseline from 100% to 1,000% over time.
Delivered fluid composition
The fluid delivered may comprise nucleic acids, viral vectors, cells, organelles, proteins, peptides, drugs, or saline-based solutions, among others, as enumerated in the patent.
Therapeutic method for treating acute kidney injury
Use of the method of delivering fluid through the renal vein catheter system to ameliorate symptoms of, or treat, acute kidney injury within about 1 to 24 hours following onset.
The claims cover a catheter with a specifically configured stabilizer and occluding balloon for controlled hydrodynamic fluid delivery, an integrated system including pumps and controllers for precise pressure and flow regulation, and methods of delivering therapeutic fluids via the renal vein using these devices. The invention focuses on stabilizing catheter placement, controlling delivery pressures, and achieving effective fluid uptake by kidney cells, claiming specific structural features, control algorithms, and treatment methods especially for acute kidney injury.
Stated Advantages
The method provides rapid and reliable delivery of multiple exogenous genes to various nephron segments with minimal injury.
It achieves widespread, stable, and lengthy transgene expression in vascular, tubular, and glomerular kidney cells.
The catheter stabilizer reduces vibratory pulsations during fluid delivery, minimizing tissue damage and fluid losses.
The system allows precise control of fluid pressure and volume to maintain efficacious delivery conditions.
The method facilitates therapeutic treatment of acute kidney injuries and ischemia/reperfusion injury.
Documented Applications
Research applications for inducing and monitoring exogenous transgene expression in live mammalian kidneys.
Gene therapy for treating or preventing kidney diseases including acute kidney injury and ischemia/reperfusion injury.
Use in ameliorating symptoms or treating kidney pathologies through hydrodynamic delivery of nucleic acids and therapeutic fluids.
Drug discovery and assay development involving kidney-targeted nucleic acid and protein delivery.
Use of kits, formulations, and compositions involving the described methods and apparatus for kidney treatments.
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