Urea Filtration Device Comprising Nanofiber Composition

Abstract

Provided herein are compositions, devices, and methods comprising a nanofiber composition comprising a polymer and nanoparticles comprising one or more of nickel, cobalt, silver, and tetraphenylborate, wherein the composition is capable of binding targets in the blood associated with a hematological disorder symptomatic of kidney disease and / or kidney failure.

Description

[Technical field]

[0001] The compositions and methods provided herein relate to nanotechnology and its medical applications. [Background technology]

[0002] The kidneys regulate the ion concentration of blood by removing harmful particles from the blood while retaining essential ions. Harmful particles absorbed from the blood and excess water are excreted from the body in urine. Under certain conditions, kidney function declines. When the kidneys lose nearly 90% of their blood purification capacity, the condition is called chronic kidney disease (CKD) and commonly leads to "end-stage renal disease (ESRD)". If left untreated, patients die from the accumulation of toxic substances in the body.

[0003] Treatment for CKD / ESRD is dialysis and / or kidney transplantation. Dialysis is the process of cleaning the blood using machines, such as hemodialysis machines, that perform the functions of the kidneys outside the body. Peritoneal dialysis is a form of hemodialysis that uses the peritoneum in a person's abdomen as a membrane to filter blood in the body.

[0004] Hemodialysis involves an average patient undergoing three to four treatments per week, with each treatment lasting three to four hours or more. Despite major advances in hemodialysis technology and the management of its complications, morbidity and mortality in dialysis patients remains high.

[0005] There remains a need to reduce patients' hemodialysis treatment times to improve patient compliance and quality of life. Summary of the Invention

[0006] In one aspect, provided herein is a nanofiber composition comprising a polymer and nanoparticles comprising one or more of nickel, cobalt, silver, and tetraphenylborate.

[0007] In one aspect, provided herein is a cartridge comprising one or more membranes, each membrane comprising a nanofiber composition comprising a polymer and one or more nanoparticles comprising nickel, cobalt, silver, and tetraphenylborate nanoparticles.

[0008] In one aspect, provided herein is a device that includes a filtration chamber configured to receive blood containing urea and one or more membranes disposed within the filtration chamber, each membrane comprising a nanofiber composition that includes a polymer and nanoparticles that include one or more of nickel, cobalt, silver, and tetraphenylborate, and the nanofibers are capable of binding urea, converting the urea to ammonia, and then binding the ammonia.

[0009] In one aspect, provided herein is a method of reducing urea concentration from blood, the method comprising: a) providing blood containing urea to a device including a cartridge, the cartridge including one or more membranes, each membrane including a nanofiber composition including a polymer and one or more of nickel, cobalt, silver, and tetraphenylborate nanoparticles; b) contacting the blood with the membranes for a sufficient amount of time to allow binding of urea and conversion of urea to ammonia; and c) pumping the blood through the cartridge at a pressure sufficient to allow binding of ammonia to the membranes, thereby reducing the concentration of urea in the blood.

[0010] In one aspect, provided herein is a method of treating a subject having a disease condition characterized by elevated blood urea levels, the method comprising: a) obtaining a blood sample from the subject; b) pumping the sample through a nanofiber composition comprising a polymer and nanoparticles comprising one or more of nickel, cobalt, silver, and tetraphenylborate for a sufficient time to allow the nanofiber composition to bind urea, convert the urea to ammonia, and then bind with the ammonia, thereby producing a filtered blood sample; and c) returning the filtered blood sample to the subject, thereby treating the subject.

[0011] In one aspect, provided herein is a method of treating a mammal for elevated blood urea levels comprising: a) delivering blood containing urea to a device comprising one or more membranes, each membrane comprising a nanofiber composition, the nanofiber composition comprising a polymer and nanoparticles comprising one or more of nickel, cobalt, silver, and tetraphenylborate, the nanofiber composition capable of binding urea, converting the urea to ammonia, and subsequently binding ammonia; b) contacting the blood with the membranes for a sufficient amount of time to allow for binding of urea and conversion to ammonia; and c) pumping the blood through a cartridge at a pressure and flow rate sufficient to allow binding of ammonia to the nanofibers, thereby reducing the concentration of urea in the blood.

[0012] In one aspect, provided herein is a method of treating a subject having a disease condition characterized by elevated blood urea levels, comprising: a) subjecting the subject to ex vivo hemofiltration by removing blood from the subject and filtering it through a device including a filtration chamber (1) configured to receive blood characterized by elevated urea levels and (2) one or more membranes, each membrane including a nanofiber composition, the nanofiber composition including one or more membranes including a polymer and one or more nanoparticles of nickel, cobalt, silver, and tetraphenylborate; b) incubating the blood with the one or more membranes for a time sufficient to allow binding of urea to the nanofiber composition, conversion of urea to ammonia, and subsequent binding of ammonia to the nanofiber composition; c) pumping the blood through the device at a pressure and flow rate sufficient to filter the blood and produce a volume of filtered blood; and d) returning the filtered blood, with at least 50% reduced urea levels, to the subject.

[0013] Provided herein is the use of any of the compositions, cartridges, and devices described herein in reducing the concentration of urea in a blood sample. [Brief description of the drawings]

[0014] [Figure 1] FIG. 1 is a schematic diagram of a typical layout of a dialysis treatment. [Diagram 2] An example of particle size analyzer results is shown, demonstrating that the particle radius of cobalt colloidal nanoparticles is approximately 96.6 nanometers. [Diagram 3] 1 shows an example of the analysis results of the zeta potential of silver nanoparticles. [Figure 4] 1 shows an example of a field emission scanning electron microscope image of silver and cobalt nanofibers with sodium tetraphenylborate. [Diagram 5] 1 shows an example of a field emission scanning electron microscope image of silicon dioxide and cobalt nanofibers with sodium tetraphenylborate. [Figure 6]1 shows an example of a field emission scanning electron microscope image of silicon dioxide and silver nanofibers with sodium tetraphenylborate. [Figure 7] 1 shows example field emission scanning electron microscope images of copper and silver nanofibers with sodium tetraphenylborate. [Figure 8] 1 shows microscopic images of blood cells exposed to silver and cobalt nanoparticles and tetraphenylborate materials. [Figure 9] 1 shows an example of an XRD pattern obtained for nickel nanofibers in a polycarbonate material. [Figure 10] 1 shows an example of an XRD pattern obtained for cobalt nanofibers in a polycarbonate material. [Figure 11] Shown are microscopic images of blood cells.The left panel is an untreated control, the middle panel is blood cells after dialysis through the dialyzer of the present disclosure at a rate of 200 ml / min, and the right panel is blood cells after dialysis through the dialyzer of the present disclosure at a rate of 300 ml / min. [Figure 12A] FIG. 1 shows an example CAD design of an example of a prototype housing for a dialyzer, showing the inside and side views of the housing. [Figure 12B] FIG. 1 shows a CAD design example of an example of a prototype housing for a dialyzer, showing the bottom side of the housing. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] definition The practice of the present technology employs, unless otherwise indicated to the contrary, conventional methods of chemistry, biochemistry, organic chemistry, molecular biology, microbiology, recombinant DNA technology, genetics, immunology and cell biology within the skill of those in the art, many of which are described below for purposes of illustration, and such techniques are fully explained in the literature.

[0016] All patents, patent applications, articles and publications cited herein supra and infra are hereby expressly incorporated by reference in their entirety.

[0017] Unless otherwise defined herein, all technical and scientific terms used herein have the same meaning as commonly understood by ordinary skilled artisans in the technical field to which this disclosure belongs. Various scientific dictionaries, including the terms contained herein, are well known and available to those skilled in the art. Although any method and material similar or equivalent to those described herein can be used in the practice or testing of this disclosure, some preferred methods and materials are described. Therefore, the terms defined below are more fully explained by referring to the entire specification. It should be understood that this disclosure is not limited to the specific methodology, protocols, and reagents described, as these may vary depending on the context in which they are used by those skilled in the art.

[0018] As used herein, the singular terms "a," "an," and "the" include plural references unless the context clearly dictates otherwise.

[0019] Throughout this specification, for example, reference to "one embodiment," "an embodiment," "another embodiment," "particular embodiment," "related embodiment," "an embodiment," "additional embodiment," or "further embodiment," or combinations thereof, means that the particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the disclosure. Thus, the appearances of such phrases in various places throughout this specification do not necessarily all refer to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

[0020] As used herein, the term "about" or "approximately" refers to a quantity, level, value, concentration, measurement, number, frequency, percentage, dimension, size, amount, weight, or length that varies by 30, 25, 20, 25, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1% from a reference quantity, level, value, concentration, measurement, number, frequency, percentage, dimension, size, amount, weight, or length. In certain embodiments, the term "about" or "approximately" when preceding a numerical value indicates a value within a range of plus or minus 15%, 10%, 5%, or 1%.

[0021] Throughout this specification, unless the context requires otherwise, the words "comprise, comprise, and / or comprising" are to be understood as meaning the inclusion of the recited step or element, or group of steps or elements, but not the exclusion of other steps or elements, or group of steps or elements. "Consisting of" means including and limited to what follows the phrase "consisting of". Thus, the phrase "consisting of" indicates that the recited elements are necessary or mandatory, and other elements may not be present. "Consisting essentially of" means including any elements recited after the phrase, and is limited to other elements that do not interfere with or contribute to the activity or action specified in the disclosure for the recited elements. Thus, the phrase "consisting essentially of" indicates that the recited elements are necessary or mandatory, but that other elements are not optional, and that other elements may or may not be present depending on whether they affect the activity or action of the recited elements.

[0022] As used herein, a "nanoparticle" is a particle having a longest dimension of 1000 nanometers or less. The longest dimension of a nanoparticle may be referred to herein as the length of the nanoparticle. The shortest dimension of a nanoparticle may be referred to herein as the width of the nanoparticle. A nanoparticle may be composed of any suitable material. For example, the nanoparticle core may comprise a suitable metal and its metal oxide (e.g., metal nanoparticle core), carbon (e.g., organic nanoparticle core), silicon and its oxide (e.g., silicon nanoparticle core), or boron and its oxide (e.g., boron nanoparticle core), or mixtures thereof. In embodiments, the nanoparticle has a shape of a sphere, rod, cube, triangle, hexagon, cylinder, spherocylinder, or ellipsoid. A nanoparticle may have a diameter. In the case of a disk-shaped nanoparticle, diameter as used herein refers to the length from one end of the disk to the other. The influence of particle morphology is intertwined with many physiochemical parameters such as size, elasticity, surface chemistry, and biological persistence. In embodiments, the nanoparticles have a diameter of about 10 to about 1000 nanometers, about 100 to about 900 nanometers, about 200 to about 800 nanometers, about 300 to about 700 nanometers, or about 400 to about 600 nanometers. In some embodiments, the nanoparticles have a diameter of about 10 to about 300 nanometers. In some embodiments, the nanoparticles have a diameter of about 30 to about 150 nanometers. In some embodiments, the nanoparticles have a diameter of about 40 to about 70 nanometers.

[0023] "Inorganic nanoparticles" is used according to its plain ordinary meaning and refers to nanoparticles that do not contain carbon. For example, inorganic nanoparticles can include metals or their metal oxides (e.g., gold nanoparticles, iron nanoparticles), silicon and its oxides (e.g., silicon dioxide nanoparticles), or titanium and its oxides (e.g., titanium dioxide nanoparticles). In an embodiment, the inorganic nanoparticles are silicon dioxide nanoparticles. In an embodiment, the inorganic nanoparticles are metal nanoparticles. In an embodiment, the nanoparticles are nickel. In an embodiment, the nanoparticles are cobalt. In an embodiment, the nanoparticles are silver. In an embodiment, the nanoparticles are tetraphenylborate. In an embodiment, the inorganic nanoparticles further include a moiety that includes carbon.

[0024] The term "silica" is used according to its plain ordinary meaning and is used interchangeably with "silicon dioxide" to refer to a composition (e.g., a solid composition such as a crystal, nanoparticle, or nanocrystal) that includes an oxide of silicon, such as a Si atom with two oxygen atoms surrounding the central Si atom (e.g., tetrahedral coordination). A nanoparticle may be composed of at least two different materials, one material (e.g., an insoluble drug) forming a core and the other material forming a shell (e.g., silica) surrounding the core. When the shell includes Si atoms, the nanoparticle may be referred to as a silica nanoparticle. Silica nanoparticles may refer to particles that include a matrix of silicon-oxygen bonds, the longest dimension of which is typically 1000 nanometers or less.

[0025] As used herein, functionalized silica nanoparticles may refer to the subsequent conjugation of moieties to the hydroxyl surface of the nanoparticle (i.e., conjugation after the formation of the silica nanoparticle). For example, the silica nanoparticles may be further functionalized to include additional atoms (e.g., nitrogen) or chemical entities (e.g., polymeric moieties or bioconjugate groups). For example, when the silica nanoparticles are further functionalized with a nitrogen-containing compound, one of the surface oxygen atoms surrounding the Si atom may be replaced with a nitrogen-containing moiety.

[0026] The term "polymer" refers to a molecule that includes repeating subunits (e.g., polymerized monomers). For example, the polymer molecule may be based on polyethylene glycol (PEG), poly[amino(1-oxo-1,6-hexanediyl)], poly(oxy-1,2-ethanediyloxycarbonyl-1,4-phenylenecarbonyl), tetraethylene glycol (TEG), polyvinylpyrrolidone (PVP), poly(xylylene), or poly(p-xylylene).

[0027] The term "poloxamer" is used according to its meaning in the art of polymer chemistry to refer to a triblock copolymer composed of a central hydrophobic block (e.g., polyoxypropylene) flanked by two hydrophilic blocks (e.g., polyoxyethylene). Poloxamers can be customized by adjusting the degree of hydrophobicity and / or hydrophilicity by extending or shortening the length of the blocks.

[0028] The term "polymerizable monomer" is used according to its meaning in the art of polymer chemistry to refer to a compound that can be chemically covalently bonded to other monomer molecules (such as other polymerizable monomers, whether the same or different) to form a polymer.

[0029] The term "branched polymer" is used according to its meaning in the art of polymer chemistry to refer to a molecule that includes repeating subunits, where at least one repeating subunit (e.g., a polymerizable monomer) is covalently linked to an additional subunit substituent (e.g., resulting from reaction with a polymerizable monomer). For example, a branched polymer can have the formula: [ka] where "A" is a first repeating subunit and "B" is a second repeating subunit. In embodiments, the first repeating subunit (e.g., polyethylene glycol) is optionally different from the second repeating subunit (e.g., polymethylene glycol).

[0030] The term "block copolymer" is used according to its ordinary meaning and refers to two or more moieties (e.g., blocks) of polymerized monomers linked by covalent bonds. In embodiments, a block copolymer is a repeating pattern of polymers. In embodiments, a block copolymer includes two or more monomers in a periodic (e.g., repeating pattern) arrangement. For example, a diblock copolymer has the formula: -BBBBBBAAAAA-, where "B" is the first subunit and "A" is the second subunit, covalently bonded together. Thus, a triblock copolymer is a copolymer having three different blocks, two of which may be the same (e.g., -AAAAABBBBBBAAAAA-) or all three of which may be different (e.g., -AAAAABBBBBBCCCCC-), where "A" is the first subunit, "B" is the second subunit, and "C" is the third subunit, covalently bonded together.

[0031] As used herein, the term "electrospinning" is used according to its plain and ordinary meaning to refer to a fiber production method in which electrical forces are used to spin electrically charged threads of a polymer solution or melt into fiber diameters on the order of a few hundred nanometers. Electrospinning combines features of both electrospraying of fibers and traditional solution dry spinning. The process does not require the use of solidification chemistry or high temperatures to produce solid threads from solution. This makes the process particularly suitable for producing fibers using large, complex molecules. Electrospinning from molten precursors has also been practiced. In this method, no solvent is carried over into the final product.

[0032] As used herein, the term "nanofiber" is used according to its plain and ordinary meaning and refers to fibers with diameters in the nanometer range. Nanofibers can be produced from different polymers and therefore have different physical properties and application possibilities. Examples of natural polymers include collagen, cellulose, silk fibroin, keratin, gelatin, polysaccharides such as chitosan and alginate. Examples of synthetic polymers include polylactic acid (PLA), polycaprolactone (PCL), polyurethane (PU), poly(lactic-co-glycolic acid) (PLGA), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), poly(ethylene-co-vinyl acetate) (PEVA), etc. The polymer chains are linked by covalent bonds. The diameter of the nanofibers depends on the type of polymer used and the method of production. All polymer nanofibers are characterized by a large surface area to volume ratio, high porosity, considerable mechanical strength, and flexible functionalization compared to the corresponding microfibers. There are various methods to create nanofibers, including drawing, electrospinning, self-assembly, template synthesis, thermally induced phase separation, etc. Electrospinning is the most commonly used method to generate nanofibers due to its simple setup, ability to mass-produce continuous nanofibers from a variety of polymers, and ability to generate ultra-fine fibers with controllable diameter, composition, and orientation.

[0033] In an embodiment, the nanofiber composition includes a polymer that provides stability. In an embodiment, the nanofiber composition includes a polymer that provides stability, the polymer being one or more of silicon dioxide, polyurethane prepolymer (PUP), polylactic acid (PLA), polycarbonate, polyvinyl alcohol (PVA), polyacrylic acid (PAA), polyethylene glycol (PEG), and polyvinylpyrrolidone (PVP). In an embodiment, the nanofiber composition includes a polymer that can bind ammonia. In an embodiment, the nanofiber composition includes a polymer that can bind ammonia, the polymer being a silicon dioxide polymer.

[0034] In embodiments described herein, nanofibers are provided that are comprised of one or more nanoparticles capable of binding urea and / or converting urea to ammonia. In embodiments described herein, nanofibers are provided that are comprised of one or more nanoparticles capable of binding urea and / or converting urea to ammonia, wherein the one or more nanoparticles are nickel nanoparticles, cobalt nanoparticles, silver nanoparticles, and / or tetraphenylborate nanoparticles.

[0035] As used herein, the term "membrane" is used according to its plain ordinary meaning to refer to a selective barrier; it allows some to pass while blocking others. Such may be molecules, ions, or other small particles. Biological membranes include cell membranes (the outer covering of cells and organelles that allows the passage of certain components), nuclear membranes that cover cell nuclei, and tissue membranes such as mucous membranes and serous membranes. Synthetic membranes are made by man for use in laboratories and industries (such as chemical plants). In the embodiments described herein, the membrane comprises a composite of nanofibers composed of polymers and nanoparticles.

[0036] As used herein, the term "cartridge" refers to a configuration or housing that can enclose the nanofibers or membranes described herein.

[0037] As used herein, the term "target" is used according to its plain and ordinary meaning and refers to a cell or molecule or region of interest that is captured by any one or more of the nanoparticles, polymers, nanofibers, compositions, and combinations thereof described herein. In an embodiment, the target is a molecule. In an embodiment, the target is a compound. In an embodiment, the target is urea. In an embodiment, the target is ammonia.

[0038] As used herein, the terms "disease" or "condition" are used according to their plain and ordinary meaning and refer to a state or condition of a patient or subject that can be treated with the compounds or methods provided herein. The disease can be a kidney disease. The disease can be a blood disease. The disease can be a condition characterized by elevated concentrations of a compound in the blood. The disease can be a condition characterized by elevated concentrations of urea in the blood.

[0039] As used herein, the term "blood disorder" or "blood disease" is used according to its plain and ordinary meaning and refers to a condition that affects one or more parts of the blood and prevents the blood from performing its role. They may be acute or chronic. Many blood disorders are hereditary. Other causes include other diseases, side effects of medicines, and deficiencies of certain nutrients in the diet. In an embodiment, the blood disorder refers to elevated urea levels.

[0040] As used herein, the term "dialysis" is used according to its plain and ordinary meaning and refers to a treatment that uses a machine to filter and purify the blood. The kidneys filter the blood by removing waste products and excess fluids from the body. This waste is sent to the bladder and passed out of the body as urine. Dialysis performs the function of the kidneys when they are not functioning properly or have failed. This helps maintain fluid and electrolyte balance when the kidneys are unable to perform their role. There are three different types of dialysis: hemodialysis, peritoneal dialysis, and continuous renal replacement therapy.

[0041] As used herein, the term "hemodialysis" is used according to its plain and ordinary meaning and refers to the process of using an artificial kidney (hemodialyzer) to remove waste products and excess fluids from the blood. Blood is drained from the body and filtered by the artificial kidney. The filtered blood is returned to the body with the help of a dialyzer. To send blood to the artificial kidney, a doctor performs surgery to create an inlet (vascular access) in the blood vessels. There are three types of inlets: 1) an arteriovenous (AV) fistula, which connects an artery to a vein; 2) an AV graft, which is a loop of tubing; and 3) a vascular access catheter, which can be inserted into a large vein in the neck. Both AV fistulas and AV grafts are designed for long-term dialysis treatment. People with AV fistulas are healed and ready to start hemodialysis in 2-3 months after surgery. People with AV grafts are ready in 2-3 weeks. The catheters are designed for short-term or temporary use. Hemodialysis treatments usually last 3-5 hours and are performed about three times a week.

[0042] As used herein, the term "peritoneal dialysis" is used according to its plain and ordinary meaning to refer to dialysis that involves surgery to implant a peritoneal dialysis (PD) catheter in the abdomen. The catheter helps filter blood through a membrane in the abdomen called the peritoneum. During treatment, a special fluid called dialysate flows into the peritoneum. The dialysate absorbs waste products. Once the dialysate has removed the waste products from the bloodstream, the waste products are drained out of the abdomen. This process takes several hours and must be repeated four to six times a day. However, the exchange of fluid can be done while the subject is asleep or awake.

[0043] As used herein, the term "continuous renal replacement therapy" or "hemofiltration" is used according to its plain and ordinary meaning and refers to a therapy used primarily in intensive care units for people with acute kidney failure. A machine pumps blood through tubes. Filters then remove waste products and water. The blood is returned to the body along with replacement fluids. The procedure is performed 12-24 hours a day, typically every day.

[0044] As used herein, the term "filtration" is used according to its plain and ordinary meaning to refer to a physical or chemical separation process in which a filter medium is used to separate solid materials and liquids from a mixture. Biological filtration may occur within an organism or may involve growing biological components on a medium in the material to be filtered. Removal of solids, emulsified components, organic chemicals, and ions is accomplished by ingestion and digestion, adsorption, or absorption. In mammals, reptiles, and birds, the kidneys function by renal filtration, where the glomeruli selectively remove undesirable components such as urea and then selectively reabsorb many substances essential to the maintenance of homeostasis in the organism. This complete process is called excretion.

[0045] As used herein, the term "urea," also known as "carbamide," has the chemical formula CO(NH 2 ) 2 The amide is an organic compound having two -NH 2 Urea plays an important role in the metabolism of nitrogen-containing compounds by animals and is the major nitrogen-containing substance in mammalian urine. It is a colorless, odorless solid that is highly soluble in water and practically non-toxic (LD 50 15 g / kg in rats. It is water-soluble and neither acidic nor alkaline. It is used in many processes in the body, especially in nitrogen excretion. The liver converts two ammonia molecules (NH 3 ) to carbon dioxide (CO 2 ) molecule to form urea.

[0046] As used herein, the term "potassium" is a mineral and an electrolyte. Potassium helps muscles, such as those that control the heartbeat and breathing, work. The body uses the potassium it needs. Any excess potassium that the body does not need is removed from the blood by the kidneys. If a subject has kidney disease, the kidneys may not be able to remove the excess potassium in an adequate manner, and too much potassium may remain in the blood. Hyperkalemia, which is too much potassium in the blood, is dangerous as it can cause a heart attack.

[0047] As used herein, the term "inhibitor" is used according to its plain and ordinary meaning to refer to a compound (e.g., a compound described herein) that reduces activity when compared to a control, such as the absence of the compound or a compound with known inactivity.

[0048] As used herein, the terms "inhibition, inhibit, inhibiting" refer to an interaction that adversely affects (e.g., reduces or inactivates or kills) the activity or function of a target. Inhibition can mean a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or more decrease in functional or viable target compared to a control in the absence of inhibitor. In some cases, expression or activity is 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 10-fold or less compared to expression or activity in the absence of antagonist.

[0049] As used herein, the term "contacting" refers to allowing two species to react, interact, or come into physical contact, where the two species can be a nanoparticle, nanofiber, nanofiber composition, or polymer described herein and a cell, a protein, an antibody, an aptamer, or another compound.

[0050] The term "treat" or "treatment" refers to indications of success in a therapy or improvement of an injury, disease, condition, or condition, including objective or subjective parameters. Objective or subjective parameters include palliative, remission, reduction of symptoms or making the injury, disease, condition, or condition more tolerable to the patient, slowing the rate of degeneration or deterioration, making the final stage of degeneration less debilitating, improving the physical or mental well-being of the patient, and the like. Treatment or improvement of symptoms can be based on objective or subjective parameters, including the results of a physical exam, a neuropsychiatric exam, and / or a psychiatric evaluation. The term "treat" and its conjugations can include prevention of an injury, disease, condition, or disease. In an embodiment, treating is preventing. In an embodiment, treating does not include preventing.

[0051] As used herein, "treating" or "treatment" (as is well understood in the art) broadly includes any approach to obtain beneficial or desired results in a subject's condition, including clinical results. Beneficial or desired clinical results may include, but are not limited to, alleviation or amelioration of one or more symptoms or pathology, reduction in the extent of disease, stabilization (i.e., not worsening) of a disease state, prevention of disease transmission or spread, delay or slowing of disease progression, improvement or palliation of a disease state, reduction in disease recurrence, and remission, whether partial or total, and whether detectable or undetectable. In other words, as used herein, "treatment" includes any cure, amelioration, or prevention of disease. Treatment may prevent the onset of disease, inhibit the spread of disease, alleviate symptoms of disease, completely or partially eliminate the underlying cause of disease, shorten the duration of disease, or a combination thereof.

[0052] As used herein, the term "prevent" refers to reducing the occurrence of disease symptoms in a patient. Prevention may be complete (no detectable symptoms) or partial, where symptoms are observed that are less severe than would likely occur in the absence of treatment. As used herein, "prevent" refers to the reduction of a target (e.g., urea) to prevent a patient from experiencing the harmful effects of elevated blood urea levels.

[0053] As used herein, the term "patient" or "subject in need thereof" refers to a living organism suffering from or susceptible to a disease or condition that can be treated by the methods or compositions provided herein. Non-limiting examples include humans, other mammals, cows, rats, mice, dogs, monkeys, goats, sheep, dairy cows, deer, and other non-mammals. In some embodiments, the patient is a human. In some embodiments, the patient is a canine. In some embodiments, the patient is a feline.

[0054] As used herein, the term "effective amount" refers to an amount of the composition described herein sufficient to achieve the stated purpose compared to the absence of the composition (e.g., achieve the effect for which it is administered, prevent infection, reduce target activity, etc.). An example of an "effective amount" is an amount sufficient to contribute to the prevention or reduction of one or more symptoms of a disease, which may also be referred to as a "therapeutically effective amount." "Reduction" of one or more symptoms (and grammatical equivalents of this phrase) refers to a decrease in the severity or frequency of symptoms associated with, for example, an increase in blood urea concentration. In embodiments, an effective amount refers to the number of nanofibers, nanoparticles, and / or membranes comprising nanofibers described herein to affect a decrease in blood urea concentration and / or bind ammonia. The exact amount will vary depending on the purpose of the treatment and will be ascertainable by one of skill in the art using known techniques.

[0055] For any of the compositions described herein, a therapeutically effective amount can be initially determined from assays that are target and filter complex concentrations that can be achieved by the methods described herein, as measured using methods described herein or known in the art.

[0056] As used herein, the term "therapeutically effective amount" refers to an amount of a therapeutic agent sufficient to improve a disorder, as described above. For example, for a given parameter, a therapeutically effective amount may exhibit an increase or decrease of at least 5%, 10%, 15%, 20%, 25%, 40%, 50%, 60%, 75%, 80%, 90%, or at least 100%. Therapeutic efficacy may also be expressed as a "fold" increase or decrease. For example, a therapeutically effective amount may have at least a 1.2-fold, 1.5-fold, 2-fold, 5-fold, or greater effect over a control.

[0057] As used herein, the term "compound" is used according to its plain and ordinary meaning and refers to a substance formed by the chemical combination of two or more chemical elements. As described herein, the compound may be a target compound. In an embodiment, the target compound is urea. In an embodiment, the target compound is ammonia.

[0058] The description of the compounds of the present disclosure is limited by the principles of chemical bonding known to those skilled in the art.Therefore, when a group may be substituted with one or more of a number of substituents, such substitutions are selected to comply with the principles of chemical bonding and to result in a compound that is known to those skilled in the art to be not inherently unstable and / or likely to be unstable under ambient conditions, such as aqueous, neutral, and some known physiological conditions.For example, heterocycloalkyl or heteroaryl is attached to the rest of the molecule via a ring heteroatom according to the principles of chemical bonding known to those skilled in the art, thereby avoiding inherently unstable compounds.

[0059] As used herein, the term "control" or "control experiment" is used according to its plain and ordinary meaning and refers to an experiment in which the experimental subjects or reagents are treated the same as in a parallel experiment, except for the omission of an experimental procedure, reagent, or variable. In some cases, a control is used as a standard of comparison when evaluating the experimental effect. In some embodiments, the control is a measurement of the infection rate in the absence of a filter as described herein (including the embodiments and examples).

[0060] As used herein, the terms "specific," "specifically," "specificity," and the like, of a composition refer to the ability of the composition to cause a particular effect, such as inhibition, on a particular molecular target while having minimal or no effect on other proteins within the cell.

[0061] As used herein, the term "solution" refers to a liquid mixture in which a minor component (e.g., a solute or compound) is uniformly distributed within a major component (e.g., a solvent). In embodiments, the solution contains nanoparticles.

[0062] As used herein, the term "organic solvent" is used according to its usual meaning in chemistry to refer to a solvent that contains carbon. Non-limiting examples of organic solvents include acetic acid, acetone, acetonitrile, benzene, 1-butanol, 2-butanol, 2-butanone, t-butyl alcohol, carbon tetrachloride, chlorobenzene, chloroform, cyclohexane, 1,2-dichloroethane, diethylene glycol, diethyl ether, diglyme (diethylene glycol, dimethyl ether), 1,2-dimethoxyethane (glyme, DME), dimethylformamide (DMF), dimethylsulfoxide (DMSO), 1,4-dioxane, ethanol, vinegar, etc. Examples of suitable organic solvents include ethyl acetate, ethylene glycol, glycerin, heptane, hexamethylphosphoramide (HMPA), hexamethylphosphortriamide (HMPT), hexane, methanol, methyl t-butyl ether (MTBE), methylene chloride, N-methyl-2-pyrrolidinone (NMP), nitromethane, pentane, petroleum ether (ligroin), 1-propanol, 2-propanol, pyridine, tetrahydrofuran (THF), toluene, triethylamine, o-xylene, m-xylene, or p-xylene. In embodiments, the organic solvent is or includes chloroform, dichloromethane, methanol, ethanol, tetrahydrofuran, or dioxane.

[0063] As used herein, the term "salt" refers to the acid salt or base salt of the compound used in the method of the present invention.Examples of acceptable salts are inorganic acid (hydrochloric acid, hydrobromic acid, phosphoric acid, etc.) salts, organic acid (acetic acid, propionic acid, glutamic acid, citric acid, etc.) salts, and quaternary ammonium (methyl iodide, ethyl iodide, etc.) salts.Examples of acceptable salts are inorganic acid (hydrochloric acid, hydrobromic acid, phosphoric acid, etc.) salts, organic acid (acetic acid, propionic acid, glutamic acid, citric acid, etc.) salts, and quaternary ammonium (methyl iodide, ethyl iodide, etc.) salts.

[0064] As used herein, the terms "bond" and "bonded" are used according to their clear and ordinary meaning and refer to a bond between atoms or molecules. The bond may be direct or indirect. For example, the bonded atoms or molecules may be directly bonded, for example, by a covalent bond or linker (e.g., a first linker or a second linker), or indirectly bonded, for example, by a non-covalent bond (e.g., electrostatic interactions (e.g., ionic bonds, hydrogen bonds, halogen bonds), van der Waals interactions (e.g., dipole-dipole, dipole-induced dipole, London dispersion), ring stacking (pi effect), hydrophobic interactions, etc.).

[0065] As used herein, the term "conjugated" when referring to two moieties means that the two moieties are linked, where the bond or bonds connecting the two moieties can be covalent or non-covalent. In embodiments, the two moieties are covalently linked to one another (e.g., directly or through a covalently linked intermediate). In embodiments, the two moieties are non-covalently linked (e.g., through ionic bond(s), van der Waals bond(s) / interaction, hydrogen bond(s), polar bond(s), or a combination or mixture thereof).

[0066] composition In one aspect, provided herein is a nanofiber composition comprising a polymer and nanoparticles comprising one or more of nickel, cobalt, silver, and tetraphenylborate.

[0067] In embodiments, the nanofiber compositions provided herein comprise a polymer, the polymer comprising one or more of silicon dioxide, polyurethane prepolymer (PUP), polylactic acid (PLA), polycarbonate, polyvinyl alcohol (PVA), polyacrylic acid (PAA), polyethylene glycol (PEG), and polyvinylpyrrolidone (PVP). In embodiments, the polymer is non-conductive. In embodiments, the polymer is silicon dioxide. In embodiments, the polymer is polyurethane prepolymer (PUP). In embodiments, the polymer is polylactic acid (PLA). In embodiments, the polymer is polycarbonate. In embodiments, the polymer is polyvinyl alcohol (PVA). In embodiments, the polymer is polyacrylic acid (PAA). In embodiments, the polymer is polyethylene glycol (PEG). In embodiments, the polymer is polyvinylpyrrolidone (PVP). In embodiments, the nanofiber compositions provided herein comprise a polymer comprising a combination of silicon dioxide, polyurethane prepolymer (PUP), polylactic acid (PLA), polycarbonate, polyvinyl alcohol (PVA), polyacrylic acid (PAA), polyethylene glycol (PEG), and polyvinylpyrrolidone (PVP). In embodiments, the nanofiber compositions provided herein comprise a polymer comprising a combination of silicon dioxide and polyvinylpyrrolidone (PVP).

[0068] In embodiments, the nanofiber compositions provided herein include a polymer and nanoparticles, the nanoparticles being comprised of one or more of nickel, cobalt, silver, and tetraphenylborate. In embodiments, the nanofiber compositions include nickel nanoparticles. In embodiments, the nanofiber compositions include cobalt nanoparticles. In embodiments, the nanofiber compositions include silver nanoparticles. In embodiments, the nanofiber compositions include tetraphenylborate nanoparticles. In embodiments, the nanofiber compositions provided herein include a polymer and nanoparticles, the nanoparticles being comprised of a combination of nickel, cobalt, silver, or tetraphenylborate. In embodiments, the nanofiber compositions provided herein include a polymer and silver and nickel nanoparticles. In embodiments, the nanofiber compositions provided herein include a polymer and silver, nickel, and tetraphenylborate nanoparticles. In embodiments, the nanofiber compositions provided herein include a polymer and silver and cobalt nanoparticles. In embodiments, the nanofiber compositions provided herein include a polymer and silver, cobalt, and tetraphenylborate nanoparticles. Nanoparticles may be spun to form nanofibers. Nanoparticles may be spun with other materials to form nanofibers.

[0069] In embodiments, the nanofiber compositions provided herein include a polymer comprised of one or more of silicon dioxide, PVP, PUP, PLA, polycarbonate, PVA, PAA, and PEG, and one or more of nickel, silver, cobalt, and tetraphenylborate nanoparticles. In embodiments, the nanofiber composition includes a polymer comprised of silicon dioxide and further includes nickel nanoparticles. In embodiments, the nanofiber composition includes a polymer comprised of silicon dioxide and further includes cobalt nanoparticles. In embodiments, the nanofiber composition includes a polymer comprised of silicon dioxide and further includes silver nanoparticles. In embodiments, the nanofiber composition includes a polymer comprised of silicon dioxide and further includes tetraphenylborate nanoparticles. In embodiments, the nanofiber composition includes a polymer comprised of silicon dioxide and further includes nickel and cobalt nanoparticles. In embodiments, the nanofiber composition includes a polymer comprised of silicon dioxide and further includes nickel and silver nanoparticles. In embodiments, the nanofiber composition includes a polymer comprised of silicon dioxide and further includes nickel and silver nanoparticles. In embodiments, the nanofiber composition includes a polymer comprised of silicon dioxide and further includes nickel and silver nanoparticles. In embodiments, the nanofiber composition includes a polymer comprised of silicon dioxide and further includes cobalt and silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising silicon dioxide and further comprises nickel, cobalt, and tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising silicon dioxide and further comprises nickel, silver, and tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising silicon dioxide and further comprises cobalt, silver, and tetraphenylborate nanoparticles.

[0070] In an embodiment, the nanofiber composition comprises a polymer comprising polyvinylpyrrolidone (PVP) and further comprises nickel nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyvinylpyrrolidone (PVP) and further comprises cobalt nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyvinylpyrrolidone (PVP) and further comprises silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyvinylpyrrolidone (PVP) and further comprises tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyvinylpyrrolidone (PVP) and further comprises nickel and cobalt nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyvinylpyrrolidone (PVP) and further comprises nickel and silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyvinylpyrrolidone (PVP) and further comprises cobalt and silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyvinylpyrrolidone (PVP) and further comprises nickel, cobalt and tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyvinylpyrrolidone (PVP) and further comprises nickel, silver, and tetraphenylborate nanoparticles.In an embodiment, the nanofiber composition comprises a polymer comprising polyvinylpyrrolidone (PVP) and further comprises cobalt, silver, and tetraphenylborate nanoparticles.

[0071] In an embodiment, the nanofiber composition comprises a polymer comprising a polyurethane prepolymer (PUP) and further comprises nickel nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising a polyurethane prepolymer (PUP) and further comprises cobalt nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising a polyurethane prepolymer (PUP) and further comprises silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising a polyurethane prepolymer (PUP) and further comprises tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising a polyurethane prepolymer (PUP) and further comprises nickel and cobalt nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising a polyurethane prepolymer (PUP) and further comprises nickel and silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising a polyurethane prepolymer (PUP) and further comprises cobalt and silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising a polyurethane prepolymer (PUP) and further comprises nickel, cobalt and tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising a polyurethane prepolymer (PUP) and further comprises nickel, silver and tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer that includes a polyurethane prepolymer (PUP) and further comprises cobalt, silver, and tetraphenylborate nanoparticles.

[0072] In an embodiment, the nanofiber composition comprises a polymer comprising polylactic acid (PLA) and further comprises nickel nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polylactic acid (PLA) and further comprises cobalt nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polylactic acid (PLA) and further comprises silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polylactic acid (PLA) and further comprises tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polylactic acid (PLA) and further comprises nickel and cobalt nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polylactic acid (PLA) and further comprises nickel and silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polylactic acid (PLA) and further comprises cobalt and silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polylactic acid (PLA) and further comprises nickel, cobalt and tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polylactic acid (PLA) and further comprises nickel, silver, and tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer that includes polylactic acid (PLA) and further comprises cobalt, silver, and tetraphenylborate nanoparticles.

[0073] In an embodiment, the nanofiber composition comprises a polymer comprising polycarbonate and further comprises nickel nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polycarbonate and further comprises cobalt nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polycarbonate and further comprises silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polycarbonate and further comprises tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polycarbonate and further comprises nickel and cobalt nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polycarbonate and further comprises nickel and silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polycarbonate and further comprises cobalt and silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polycarbonate and further comprises nickel, cobalt and tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polycarbonate and further comprises nickel, silver and tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polycarbonate and further comprises cobalt, silver, and tetraphenylborate nanoparticles.

[0074] In an embodiment, the nanofiber composition comprises a polymer comprising polyvinyl alcohol (PVA) and further comprises nickel nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyvinyl alcohol (PVA) and further comprises cobalt nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyvinyl alcohol (PVA) and further comprises silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyvinyl alcohol (PVA) and further comprises tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyvinyl alcohol (PVA) and further comprises nickel and cobalt nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyvinyl alcohol (PVA) and further comprises nickel and silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyvinyl alcohol (PVA) and further comprises cobalt and silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyvinyl alcohol (PVA) and further comprises nickel, cobalt and tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyvinyl alcohol (PVA) and further comprises nickel, silver and tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer that includes polyvinyl alcohol (PVA) and further comprises cobalt, silver, and tetraphenylborate nanoparticles.

[0075] In an embodiment, the nanofiber composition comprises a polymer comprising polyacrylic acid (PAA) and further comprises nickel nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyacrylic acid (PAA) and further comprises cobalt nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyacrylic acid (PAA) and further comprises silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyacrylic acid (PAA) and further comprises tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyacrylic acid (PAA) and further comprises nickel and cobalt nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyacrylic acid (PAA) and further comprises nickel and silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyacrylic acid (PAA) and further comprises cobalt and silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyacrylic acid (PAA) and further comprises nickel, cobalt and tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyacrylic acid (PAA) and further comprises nickel, silver and tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer that includes polyacrylic acid (PAA) and further comprises cobalt, silver, and tetraphenylborate nanoparticles.

[0076] In an embodiment, the nanofiber composition comprises a polymer comprising polyethylene glycol (PEG) and further comprises nickel nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyethylene glycol (PEG) and further comprises cobalt nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyethylene glycol (PEG) and further comprises silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyethylene glycol (PEG) and further comprises tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyethylene glycol (PEG) and further comprises nickel and cobalt nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyethylene glycol (PEG) and further comprises nickel and silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyethylene glycol (PEG) and further comprises cobalt and silver nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyethylene glycol (PEG) and further comprises nickel, cobalt and tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer comprising polyethylene glycol (PEG) and further comprises nickel, silver, and tetraphenylborate nanoparticles. In an embodiment, the nanofiber composition comprises a polymer that includes polyethylene glycol (PEG) and further comprises cobalt, silver, and tetraphenylborate nanoparticles.

[0077] In embodiments, the nanofiber compositions described herein are capable of binding urea. In embodiments, the nanofiber compositions described herein are capable of converting urea to ammonia. In embodiments, the nanofiber compositions described herein are capable of binding ammonia. In embodiments, the nanofiber compositions described herein are capable of binding urea, converting urea to ammonia, and binding ammonia.

[0078] In embodiments, provided herein are nanofiber compositions comprised of nanoparticles, the nanoparticles having a diameter of about 5 to about 1000 nanometers. In embodiments, the nanoparticles have an average diameter of about 10 to about 1000 nanometers, about 100 to about 900 nanometers, about 200 to about 800 nanometers, about 300 to about 700 nanometers, or about 400 to about 600 nanometers. In some embodiments, the nanoparticles have a diameter of about 10 to about 500 nanometers, about 20 to about 400 nanometers, about 30 to about 300 nanometers, about 40 to about 200 nanometers, or about 50 to about 100 nanometers. In some embodiments, the nanoparticles have an average diameter of about 10 to about 250, about 20 to about 200, about 30 to about 150, or about 40 to about 100 nanometers. In some embodiments, the nanoparticles have an average diameter of about 10 nanometers, about 20 nanometers, about 30 nanometers, about 40 nanometers, about 50 nanometers, about 60 nanometers, about 70 nanometers, about 80 nanometers, about 90 nanometers, about 100 nanometers, about 110 nanometers, about 120 nanometers, about 130 nanometers, about 140 nanometers, about 150 nanometers, about 160 nanometers, about 170 nanometers, about 180 nanometers, or about 190 nanometers. In some embodiments, the nanoparticles have a diameter of about 200 nanometers, about 300 nanometers, about 400 nanometers, about 500 nanometers, about 600 nanometers, about 700 nanometers, about 800 nanometers, about 900 nanometers, or about 1000 nanometers. In some embodiments, the nanoparticles have a diameter of about 10 to about 300. In some embodiments, the nanoparticles have an average diameter of about 20 to about 150 nanometers. In some embodiments, the nanoparticles have an average diameter of about 40 to about 70 nanometers. In some embodiments, the nanoparticles have a diameter of about 10 nanometers. In some embodiments, the nanoparticles have an average diameter of about 20 nanometers. In some embodiments, the nanoparticles have an average diameter of about 30 nanometers. In some embodiments, the nanoparticles have an average diameter of about 40 nanometers.In some embodiments, the nanoparticles have an average diameter of about 50 nanometers. In some embodiments, the nanoparticles have an average diameter of about 60 nanometers. In some embodiments, the nanoparticles have a diameter of about 70 nanometers. In some embodiments, the nanoparticles have an average diameter of about 80 nanometers. In some embodiments, the nanoparticles have a diameter of about 90 nanometers. In some embodiments, the nanoparticles have an average diameter of about 100 nanometers. In some embodiments, the nanoparticles have an average diameter of about 110 nanometers. In some embodiments, the nanoparticles have an average diameter of about 120 nanometers. In some embodiments, the nanoparticles have a diameter of about 130 nanometers. In some embodiments, the nanoparticles have an average diameter of about 140 nanometers. In some embodiments, the nanoparticles have an average diameter of about 150 nanometers. The diameter of the nanoparticles can be any value or subrange within the recited range, including the endpoints.

[0079] In embodiments, provided herein are nanofiber compositions in which polymers and nanoparticles are woven together by electrospinning to form fibers.

[0080] Nanofiber Production In one aspect, provided herein are nanofiber compositions produced by electrospinning.

[0081] film In one aspect, provided herein is a membrane comprised of the nanofiber composition described herein. The membrane can be arranged to form a filter or membrane composite. The filter or membrane composite can be housed in a cartridge or placed in a device such as a dialyzer used in a hemodialysis or peritoneal dialysis machine.

[0082] In embodiments, provided herein are membranes comprising nanofibers, the nanofibers comprising a polymer and one or more of nickel nanoparticles, cobalt nanoparticles, silver nanoparticles, and tetraphenylborate nanoparticles. In embodiments, the membrane comprises nanofibers comprising a polymer, the polymer comprising one or more of silicon dioxide, polyvinylpyrrolidone (PVP), polyurethane prepolymer (PUP), polylactic acid (PLA), polycarbonate, polyvinyl alcohol (PVA), polyacrylic acid (PAA), and polyethylene glycol (PEG). In embodiments, the polymer is non-conductive. In embodiments, the polymer is silicon dioxide. In embodiments, the polymer is polyvinylpyrrolidone (PVP). In embodiments, the polymer is polyurethane prepolymer (PUP). In embodiments, the polymer is polylactic acid (PLA). In embodiments, the polymer is polycarbonate. In embodiments, the polymer is polyvinyl alcohol (PVA). In embodiments, the polymer is polyacrylic acid (PAA). In embodiments, the polymer is polyethylene glycol (PEG). In an embodiment, the polymers are silicon dioxide and polyvinylpyrrolidone (PVP).

[0083] In embodiments, provided herein is a membrane comprising the nanofibers described herein. Specifically, the nanofibers include a polymer and nanoparticles, the nanoparticles being comprised of one or more of nickel, cobalt, silver, and tetraphenylborate. In embodiments, the nanoparticles are nickel. In embodiments, the nanoparticles are cobalt. In embodiments, the nanoparticles are silver. In embodiments, the nanoparticles are tetraphenylborate. In embodiments, the nanoparticles are nickel and silver. In embodiments, the nanoparticles are cobalt and silver. In embodiments, the nanoparticles are nickel and cobalt. In embodiments, the nanoparticles are nickel, silver, and tetraphenylborate. In embodiments, the nanoparticles are cobalt, silver, and tetraphenylborate. In embodiments, the nanoparticles are nickel, cobalt, and tetraphenylborate. The nanoparticles may be spun to form nanofibers. The nanoparticles may be spun with other materials to form nanofibers.

[0084] In embodiments, provided herein is a SiO 2 and silver and cobalt nanoparticles, further comprising tetraphenylborate nanoparticles. In embodiments, provided herein is a membrane comprising nanofibers comprising a polymer comprising PVP, silver and cobalt nanoparticles, further comprising tetraphenylborate nanoparticles. In embodiments, provided herein is a membrane comprising nanofibers comprising a polymer comprising PVP, silver and cobalt nanoparticles, further comprising tetraphenylborate nanoparticles. In embodiments, provided herein is a membrane comprising nanofibers comprising a polymer comprising SiO 2 and silver and nickel nanoparticles, further comprising tetraphenylborate nanoparticles. In embodiments, provided herein is a membrane comprising nanofibers comprising a polymer comprising PVP, silver and nickel nanoparticles, further comprising tetraphenylborate nanoparticles.

[0085] In embodiments, provided herein are membranes comprised of nanofibers, the nanofibers capable of binding urea, converting urea to ammonia, and / or binding ammonia. In embodiments, the nanofibers capable of binding urea and converting urea to ammonia. In embodiments, nanofibers comprised of one or more of nickel, cobalt, and silver nanoparticles capable of binding urea and converting urea to ammonia. In embodiments, the nanofibers capable of binding ammonia. In embodiments, nanofibers comprised of one or more of silicon dioxide and tetraphenylborate capable of binding ammonia.

[0086] Device In one aspect, provided herein is a cartridge comprising one or more membranes, each membrane comprising a nanofiber composition comprising a polymer and one or more nanoparticles comprising nickel, cobalt, silver, and tetraphenylborate nanoparticles.

[0087] In embodiments, the membrane of the cartridge provided herein comprises nanofibers comprising a polymer, the polymer comprising one or more of silicon dioxide, polyurethane prepolymer (PUP), polylactic acid (PLA), polycarbonate, polyvinyl alcohol (PVA), polyacrylic acid (PAA), PEG, and PVP. In embodiments, the polymer is non-conductive. In embodiments, the polymer is silicon dioxide. In embodiments, the polymer is polyurethane prepolymer (PUP). In embodiments, the polymer is polylactic acid (PLA). In embodiments, the polymer is polycarbonate. In embodiments, the polymer is polyvinyl alcohol (PVA). In embodiments, the polymer is polyacrylic acid (PAA). In embodiments, the polymer is polyethylene glycol (PEG). In embodiments, the polymer is polyvinylpyrrolidone (PVP). In an embodiment, the membrane of the cartridge provided herein comprises a nanofiber comprising a polymer, the polymer comprising a combination of silicon dioxide, polyurethane prepolymer (PUP), polylactic acid (PLA), polycarbonate, polyvinyl alcohol (PVA), polyacrylic acid (PAA), polyethylene glycol (PEG), and polyvinylpyrrolidone (PVP). In an embodiment, the membrane of the cartridge provided herein comprises a nanofiber comprising a polymer, the polymer comprising a combination of silicon dioxide and polyvinylpyrrolidone (PVP).

[0088] In embodiments, the membrane of the cartridge provided herein comprises a nanofiber comprising a polymer and nanoparticles, the nanoparticles being comprised of one or more of nickel, cobalt, silver, and tetraphenylborate. In embodiments, the nanoparticles are nickel. In embodiments, the nanoparticles are cobalt. In embodiments, the nanoparticles are silver. In embodiments, the nanoparticles are tetraphenylborate. The nanoparticles may be spun to form the nanofibers. The nanoparticles may be spun with other materials to form the nanofibers.

[0089] In embodiments, provided herein is a cartridge comprised of a membrane comprising nanofibers, the nanofibers being comprised of silicon dioxide (SiO 2 In an embodiment, provided herein is a cartridge comprised of a membrane comprising nanofibers, the nanofibers being comprised of silicon dioxide (SiO 2 ) polymer and silver and cobalt nanoparticles. In embodiments, provided herein is a cartridge comprised of a membrane further comprising tetraphenylborate nanoparticles.

[0090] In embodiments, provided herein is a cartridge comprising one or more membranes comprised of the nanofibers described herein, wherein the nanofibers are capable of binding urea, converting the urea to ammonia, and binding ammonia.

[0091] In one aspect, provided herein is a device that includes a filtration chamber configured to receive blood containing urea and one or more membranes disposed within the filtration chamber, each membrane comprising a nanofiber composition that includes a polymer and nanoparticles that include one or more of nickel, cobalt, silver, and tetraphenylborate, and the nanofibers are capable of binding urea, converting the urea to ammonia, and then binding the ammonia.

[0092] In embodiments, a membrane disposed within the device comprises a nanofiber composition described herein.

[0093] In embodiments, the devices provided herein are wearable.

[0094] In embodiments, the devices provided herein are formatted for extracorporeal filtration.

[0095] How to use In one aspect, provided herein is a method of reducing urea concentration from blood, the method comprising: a) providing blood containing urea to a device including a cartridge, the cartridge including one or more membranes, each membrane including a nanofiber composition, the nanofiber composition including a polymer including one or more of silicon dioxide, polyvinylpyrrolidone (PVP), polyurethane prepolymer (PUP), polylactic acid (PLA), polycarbonate, polyvinyl alcohol (PVA), polyacrylic acid (PAA), and polyethylene glycol (PEG), and one or more of nickel, cobalt, silver, and tetraphenylborate nanoparticles; b) contacting the blood with the membrane for a sufficient amount of time to allow binding of urea and conversion of urea to ammonia; and c) pumping the blood through the cartridge at a pressure sufficient to allow binding of ammonia to the membrane, thereby reducing the concentration of urea in the blood.

[0096] In one aspect, provided herein is a method of treating a subject having a disease condition characterized by elevated blood urea levels, the method comprising: a) obtaining a blood sample from the subject; b) pumping the sample through a nanofiber composition comprising a polymer and nanoparticles comprising one or more of nickel, cobalt, silver, and tetraphenylborate for a sufficient time to allow the nanofiber composition to bind urea, convert the urea to ammonia, and then bind with the ammonia, thereby producing a filtered blood sample; and c) returning the filtered blood sample to the subject, thereby treating the subject.

[0097] In one aspect, provided herein is a method of treating a mammal for elevated blood urea levels comprising: a) delivering blood containing urea to a device comprising one or more membranes, each membrane comprising a nanofiber composition, the nanofiber composition comprising a polymer comprising one or more of silicon dioxide, polyvinylpyrrolidone (PVP), polyurethane prepolymer (PUP), polylactic acid (PLA), polycarbonate, polyvinyl alcohol (PVA), polyacrylic acid (PAA), and polyethylene glycol (PEG), and nanoparticles comprising one or more of nickel, cobalt, silver, and tetraphenylborate, the nanofiber composition capable of binding urea, converting the urea to ammonia, and subsequently binding ammonia; b) contacting the blood with the membranes for an amount of time sufficient to allow for binding and conversion of urea to ammonia; and c) pumping the blood through the cartridge at a flow rate sufficient to allow binding of ammonia to the nanofibers, thereby reducing the concentration of urea in the blood.

[0098] In one aspect, provided herein is a method of treating a subject having a disease state characterized by elevated blood urea levels, comprising: a) withdrawing blood from the subject, the method being configured to (1) receive blood characterized by elevated urea levels; and (2) receiving one or more membranes, each membrane comprising a nanofiber composition, the nanofiber composition comprising a polymer comprising one or more of silicon dioxide, polyvinylpyrrolidone (PVP), polyurethane prepolymer (PUP), polylactic acid (PLA), polycarbonate, polyvinyl alcohol (PVA), polyacrylic acid (PAA), and polyethylene glycol (PEG), and one or more nanofibers comprising nickel, cobalt, silver, and tetraphenylborate. and (b) incubating the blood with the one or more membranes for a time sufficient to allow binding of urea to the nanofiber composition, conversion of the urea to ammonia, and subsequent binding of the ammonia to the nanofiber composition; c) pumping the blood through the device at a flow rate sufficient to filter the blood and produce a quantity of filtered blood; and d) returning the filtered blood, with the urea concentration reduced by at least 50%, to the subject.

[0099] In embodiments, provided herein is a method comprising supplying blood, where supplying blood is accomplished by pumping blood from a subject to any one of the various embodiment devices described herein.

[0100] Pumping of the blood can be accomplished using a standard medical grade pump.

[0101] In embodiments, provided herein are methods of contacting a blood sample with any one of the various membranes described herein for a time sufficient for binding of urea and conversion of urea to ammonia. In embodiments, the sufficient time is about 5 minutes to about 2 hours. In embodiments, the sufficient time is 10 minutes. In embodiments, the sufficient time is 15 minutes. In embodiments, the sufficient time is 20 minutes. In embodiments, the sufficient time is 25 minutes. In embodiments, the sufficient time is 30 minutes. In embodiments, the sufficient time is 35 minutes. In embodiments, the sufficient time is 40 minutes. In embodiments, the sufficient time is 45 minutes. In embodiments, the sufficient time is 50 minutes. In embodiments, the sufficient time is 55 minutes. In embodiments, the sufficient time is 60 minutes. In embodiments, the sufficient time is 65 minutes. In embodiments, the sufficient time is 70 minutes. In embodiments, the sufficient time is 75 minutes. In embodiments, the sufficient time is 80 minutes. In embodiments, the sufficient time is 85 minutes. In embodiments, the sufficient time is 90 minutes. In embodiments, the sufficient time is 95 minutes. In embodiments, the sufficient time is 100 minutes. In an embodiment, a sufficient time is 105 minutes. In an embodiment, a sufficient time is 110 minutes. In an embodiment, a sufficient time is 115 minutes. In an embodiment, a sufficient time is 120 minutes.

[0102] In embodiments, provided herein is a method of pumping a blood sample through a cartridge described herein at a flow rate sufficient to allow binding of ammonia to the membrane, thereby reducing urea concentration in the blood. In embodiments, the sufficient flow rate is about 25 milliliters of blood per minute (ml / min) to about 400 milliliters of blood per minute (ml / min). In embodiments, the sufficient flow rate is about 50 ml / min. In embodiments, the sufficient flow rate is about 100 ml / min. In embodiments, the sufficient flow rate is about 150 ml / min. In embodiments, the sufficient flow rate is about 200 ml / min. In embodiments, the sufficient flow rate is about 250 ml / min. In embodiments, the sufficient flow rate is about 300 ml / min. In embodiments, the sufficient flow rate is about 350 ml / min. In embodiments, the sufficient flow rate is about 400 ml / min.

[0103] In an embodiment, provided herein is a method of treating a subject having a disease state characterized by elevated blood urea concentration, wherein the disease is renal failure, chronic kidney disease (CKD), acute kidney injury (AKI), or end-stage renal disease (ESRD). In an embodiment, the disease is renal disease. In an embodiment, the disease is chronic kidney disease (CKD). In an embodiment, the disease is acute kidney injury (AKI). In an embodiment, the disease is end-stage renal disease (ESRD).

[0104] In embodiments, provided herein are methods of treating a subject that involve pumping a blood sample of the subject through a nanofiber composition comprising a polymer and nanoparticles comprising one or more of nickel, cobalt, silver, and tetraphenylborate for a time sufficient to allow the nanofiber composition to bind urea, convert the urea to ammonia, and then bind the ammonia, thereby creating a filtered blood sample. In embodiments, pumping may be accomplished using standard medical grade pumps known in the art. In embodiments, the time sufficient to allow the nanofiber composition to bind urea, convert the urea to ammonia, and then bind the ammonia, thereby creating a filtered blood sample, is from about 5 minutes to about 2 hours.

[0105] In embodiments, a method of using the device includes utilizing a device containing any of the described nanofiber compositions and waiting a sufficient amount of time for the composition to bind to a target. In embodiments, the target is one or more of urea and ammonia. In embodiments, a sufficient amount of time includes from about 1 minute to about 1 hour. In embodiments, a sufficient amount of time includes 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, or more than 10 minutes. In embodiments, a sufficient amount of time includes 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, or about 60 minutes. In embodiments, a sufficient amount of time includes from about 1 hour to about 24 hours. In embodiments, a sufficient amount of time includes about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 11 hours, about 12 hours, or more than about 12 hours. In embodiments, a sufficient amount of time includes from about 12 hours to about 24 hours, hi embodiments, a sufficient amount of time includes about 12 hours, about 13 hours, about 14 hours, about 15 hours, about 16 hours, about 17 hours, about 18 hours, about 19 hours, about 20 hours, about 21 hours, about 22 hours, about 23 hours, about 24 hours, or more than about 24 hours.

[0106] In embodiments, provided herein are methods of treating a subject involving returning a filtered blood sample to the subject, thereby treating the subject, In embodiments, returning the filtered blood involves pumping the filtered blood back to the subject using standard medical grade pumps known in the art.

[0107] Provided herein is the use of any of the compositions, cartridges, and devices described herein in reducing the concentration of urea in a blood sample. EXAMPLES

[0108] Example 1. Study Design

[0109] Despite great advances in hemodialysis technology and the management of its complications, morbidity and mortality in dialysis patients remains high (Kidney Int Rep. 2020 Nov;5(11): 1856-1869). In addition, the time required for recovery after dialysis can be twice as long as the duration of treatment, during which time patients complain of feeling unwell, lethargic, and depressed, and most patients are unable to hold full-time work. More importantly, the life expectancy of patients with end-stage renal disease has hardly improved in the past 20 years, and has changed little (less than one year increase) in patients over the age of 50. The goal of the experiments described herein is to improve the removal of urea from the blood and reduce patients' hemodialysis treatment times to less than half of their current time. These goals are to improve both the health outcomes and the quality of life of people undergoing hemodialysis.

[0110] Blood contains particles of various sizes and types, including cells, proteins, dissolved ions, and organic waste products. Some of these particles, such as proteins like hemoglobin, are essential to the body. Others, such as urea, creatinine, potassium, phosphorus, and excess water, must be removed from the blood or kept within certain limits, otherwise they will accumulate and inhibit normal metabolic processes. (https: / / www.urmc.rochester.edu / encyclopedia / content.aspx?ContentTypeID=90&ContentID=P02316)

[0111] The experiments contemplated herein were directed to providing a cartridge comprising a nanofiber composition comprising a polymer and multivalent nanoconjugates of one or more nanoparticles of nickel, silver, cobalt, and tetraphenylborate for removing urea from blood by first binding urea in the blood, hydrolyzing the urea (i.e., converting urea to ammonia), and then binding the ammonia, thereby producing blood with reduced urea concentrations.

[0112] Substituting the blood urea reducing nanoparticle composition for existing dialysis equipment reduces dialysis time from four (4) hours to less than two (2) hours by shortening urea removal time. It also has the advantage of nearly doubling the number of patients treated without additional capital costs. Thus, potentially reducing treatment costs (and / or reimbursement costs) for patients and improving return on investment (ROI) for service providers. Most importantly, the reduced treatment time improves patient compliance and quality of life.

[0113] As the procedure is illustrated in the schematic diagram of FIG. 1, blood first enters a urea filtration cartridge. Urea is converted to ammonia within the nanofiber composition contained within the cartridge. The blood is then absorbed in situ by the nanofibers as described herein. The blood flows through the cartridge. The cartridge includes a nanofiber composition, which includes a polymer and, optionally, one or more mutually exclusive layers of nickel, silver, cobalt, and tetraphenylborate nanoparticles. In one embodiment, when the nanofiber composition includes a polymer of silicon dioxide and a polymer of PVP, and includes silver and cobalt nanoparticles, the silver or cobalt reacts with the urea in the blood. The urea converts to ammonia and CO. 2 The silicon dioxide and tetraphenylborate absorb the free ammonia generated during the decomposition of urea. Blood flows through the cartridge several times at about 100 ml / min to about 300 ml / min for about 5 minutes to about 120 minutes.

[0114] The nanofiber-based material described herein binds and converts urea to ammonia, which is captured by the tetraphenylborate material, after which blood with reduced urea concentration is obtained and returned to the subject.

[0115] This nanofiber-based blood urea reduction cartridge has been shown to efficiently remove urea from the blood and reduce treatment time from four hours to less than one hour.

[0116] The rationale for designing the nanofiber cartridge is: a) minimum possible damage to blood cells: the minimum size of the blood passing through the cartridge must be such that blood cells are not damaged during the treatment. b) blood flow rate must be well matched with hemodialysis so that the maximum and minimum blood flow rates through the cartridge do not lead to clotting or cell damage. c) structural stability: the nanoparticles used in the cartridge manufacture must not be expelled and pumped into the subject with the treated blood. d) the surface area provided must ensure the maximum possible contact of the active substances with the flowing blood in order to maximize the removal of waste products while minimizing the treatment time.

[0117] At the same time, the cartridge was required to have uniform interfiber spacing and uniform fiber profile. In addition, mechanical strength was also required. There was a problem that winding the fibers at high speeds would result in aligned fibers that are likely to have uniform interfiber spacing but have low mechanical strength, while winding the fibers at low speeds would result in non-aligned (random) fibers that have high mechanical strength but may not have uniform interfiber spacing.

[0118] To test its safety and effectiveness, studies were conducted in dogs and rabbits: the first study was conducted in dogs and the second study in rabbits.

[0119] Example 2: Nanoparticle testing

[0120] The artificial kidney approach was to create a cartridge containing nanostructures of metals such as nickel, cobalt, silver, or combinations thereof, in a matrix capable of catalyzing the conversion of urea to ammonia. An additional layer of tetraphenylborate, known to quantitatively absorb ammonia, was also used. After screening many metal nanoconjugates, it was found that silver and nickel nanofibers, as well as silver and cobalt, were the most efficient matrices for the conversion of urea to ammonia. A surprising discovery was that the silicon dioxide polymer used to give stability to the nanofibers was also able to bind ammonia.

[0121] Experiments were conducted to develop and validate a commercially scalable process for creating silver and cobalt nanofibers that can be incorporated into 3D printed cartridges. The structures were characterized by Fourier transform infrared spectroscopy (FT-IR). The nanofiber conjugates were analyzed using field emission electron microscopy (Figures 4-7). The matrix was shown to effectively remove urea from blood both in vitro and in vivo (see Tables 1-4 below). Creatinine was effectively removed when copper-silver nanoconjugates were introduced into the cartridge. The stability of the cartridge matrix was analyzed for leaching and thermal stability. The matrix was also tested for cytotoxicity. Freshly synthesized nanofibers were used for toxicity testing. These nanofibers were exposed to blood for 3 hours and observed under a microscope. The results showed that the cells were healthy and normal after 1 hour (Figure 8) and up to 3 hours (data not shown).

[0122] The effectiveness of the material was tested in animals with kidney disease, and limited studies conducted in dogs and rabbits showed that it effectively removed urea within an hour without adversely affecting hematopoietic cells and clinical chemistry.

[0123] Herein, we describe experiments supporting the proof-of-concept of a nanofiber-based cartridge for lowering blood urea concentrations and shortening treatment time from 4 hours to an estimated 1 hour.

[0124] Synthesis of silver nanoparticles

[0125] The desired amount of silver nitrate was dissolved in absolute ethanol ([Ag2+] = 0.056M, 0.111M and 0.333M) (Solution A). Another mixture was obtained by mixing together potassium hydroxide and hydrazine monohydrate (molar ratio of N2H4 / Ag2+ = 2.5, 5 and 10) (Solution B). Then, solution A was poured into solution B and vigorous magnetic stirring was continued at room temperature. The total reaction time was about 2 hours. The obtained product was thoroughly washed with deionized water to remove reaction residues, followed by washing with acetone. Finally, the black particles were immersed in acetone and placed in a closed bottle for further characterization.

[0126] Cobalt and Silver Nanoparticles

[0127] The colloidal solution of silver particles was mixed with 1.5 mmol of Co. 2 (CO) 8 (530 mg, 0.5 equiv.) was added. The solution was kept at 120 °C for 10 min, then the temperature was increased to 180 °C and kept for 1 h. The solution was then kept at room temperature and the nanoparticles (NPs) were collected with a magnet. The NPs were redispersed in hexane (5 mL) and washed four times by adding 50 mL of isopropanol.

[0128] Nanoparticle Analysis

[0129] Particle size analysis of cobalt nanoparticles: The nanoparticles were analyzed using a particle size analyzer. The average particle size was 96.6 nm (see, for example, Figure 2).

[0130] Silver nanoparticles: The zeta potential of the silver nanoparticles was −43.8 mV (FIG. 3).

[0131] Example 3: Estimation of urea from blood

[0132] Effect of silver on blood urea

[0133] Blood samples were taken from the pathology laboratory for the experiment. BUN (Blood Urea Nitrogen) values ​​were estimated from blood in the presence of silver nanoparticles. Blood was distributed into six different test tubes (1 ml in each test tube) containing 0, 0.25, 0.5, 1, 1.5, and 2 μg / mL of silver nanoparticles (Table 1). After 2 minutes of incubation at room temperature, the BUN values ​​were measured using a biochemical analyzer (Table 1). The data show that after the addition of 1 μg / mL of silver nanoparticles, 1 ± 0.5 mMol / L of urea was degraded from blood.

[0134] [Table 1]

[0135] Effect of cobalt on blood urea

[0136] Blood samples obtained from the pathology laboratory were used for the experiment. BUN (blood urea nitrogen) values ​​were estimated from blood containing cobalt nanoparticles. Blood was distributed into six different test tubes (1 ml in each test tube) containing 0, 0.25, 0.5, 1, 1.5 and 2 μg / mL-1 of cobalt nanoparticles. After 2 min of incubation at room temperature, the BUN values ​​were measured using a biochemical analyzer (Table 2). The data show that 0.5 μg / mL of cobalt nanoparticles degraded urea to 0.4 ± 0.02 mMol / L.

[0137] [Table 2]

[0138] Absorption of ammonia by silicon dioxide polymers

[0139] Ammonia is mixed with silicon dioxide nanoparticles (SiO 2 Ammonia was estimated by the Nessler's reagent method in the presence of (NH 3 -N 5 ml / 100ml dH 2A stock solution of 0 (50 mg / L) was prepared. 5 ml (5 mg / L) of ammonia stock solution was added to four test tubes. To these tubes, 0, 10, 25, and 50 μg / mL of silicon dioxide nanoparticles were added. After 5 min of incubation at room temperature, 1 mL of potassium sodium tartrate (filtered before use) and 1 mL of Nessler's reagent were added to each test tube. The test tubes were kept at room temperature for 5 min and the optical density was measured at 425 nm (Table 3). The data indicated that the silicon dioxide polymer itself binds ammonia.

[0140] [Table 3]

[0141] Estimation of ammonia in the presence of sodium tetraphenylborate.

[0142] Sodium tetraphenylborate resin has been used for the reduction of ammonia (Cameron et al., 2002). Experiments were carried out to test whether sodium tetraphenylborate nanoparticles are suitable for the removal of ammonia produced from the reduction of urea. Ammonia was estimated by the Nessler's reagent method in the presence of sodium tetraphenylborate. Ammonia solution of 5 mg / L was used for the assay. The data showed that in the presence of 8 μg / mL sodium tetraphenylborate, ammonia was estimated to be about 1.30 mg / L (Table 4) and was therefore absorbed from the starting amount. The conclusion drawn from this data is that sodium tetraphenylborate nanoparticles bind ammonia, resulting in a significant reduction in ammonia concentration.

[0143] [Table 4]

[0144] Example 3: Preparation of nanofibers

[0145] Nanofibers containing silver, cobalt, tetraphenylborate, and PVP

[0146] Silver nitrate (AgNO 3 ) (Sigma-Aldrich), cobalt nitrate (Co(NO 3 ) 2 ) (Sigma-Aldrich) and a mixture of the stabilizer polyvinylpyrrolidone (PVP) (0.01% w / v ratio) and 1 mM sodium tetraphenylborate (TPB) solution were used as the base to prepare solutions with varying salt-to-polymer ratios. 3 and Co(NO 3 ) 2 A typical solution was prepared by adding 1 ml of water and mixing with magnetic stirring for 30 minutes, followed by adding 1 ml of acetic acid and magnetic stirring for another 30 minutes. Acetic acid was added to avoid hydrolysis of PVA. Then, five (5) grams of 15% (weight percent) PVA aqueous solution was added and vigorously magnetically stirred until a viscous homogenous solution was formed. The resulting solution was transferred into a plastic syringe tipped with a gauge 20 (inner diameter = 0.603 mm) stainless steel needle. ESPIN Nano (V2) (India) was used for electrospinning. The nozzle-collector distance was kept constant at 10 cm, the voltage was 22 kV, and the solution flow rate was kept constant at 0.5 ml / hr. Electrospinning was performed at room temperature and the relative humidity during the process was recorded to be nearly 69%. The fibers were collected on fine aluminum foil for characterization. The samples were left in an oven at 80°C overnight to remove moisture and then calcined in an oven at 475°C for 2 hours under ambient conditions. The heating rate was 5° C. / min and at the end of the calcination cycle the furnace was cooled to room temperature before removing the samples.

[0147] Cobalt, tetraphenylborate, PVP and SiO 2 Nanofibers containing

[0148] In a typical procedure, 4.80 grams of ethanol and 6.87 grams of acetic acid were mixed as a base solution, followed by the addition of a mixture of stabilizers PVP (0.01% w / v ratio) and 1 mM sodium tetraphenylborate (TPB) solution to adjust the viscosity. The mixture was stirred at 30 °C for 6 hours to ensure that the PVP was dissolved. Co(NO3 ) 2 and TEOS (tetraethyl orthosilicate, 98% purity, Sigma Aldrich) were added to the solution and stirred for 1 h to obtain Co(NO 3 ) 2 / PVP precursor solution was obtained. Co(NO 3 ) 2 The PVP / PVP precursor solution was fed into a steel-tipped needle at a constant feed rate of 0.2 mm / min. The needle was connected to a high-voltage power supply and placed horizontally on a clamp, and a flat aluminum foil was placed 15 cm from the needle tip to collect the nanofibers. When a voltage of 20 kV was applied, the droplet of precursor solution at the tip became highly charged, and the induced charges were uniformly distributed on its surface. As a result, the droplet was elongated into a thread due to both electrostatic repulsion between the surface charges and Coulomb forces due to the electric field. At the same time, the diameter of the fiber was reduced from micrometers to nanometers due to the evaporation of the solvent. The nanofibers were then adsorbed onto a collector in the form of a nonwoven mat.

[0149] Silver, tetraphenylborate, PVP, and SiO 2 Nanofibers containing

[0150] To prepare the dope solution, TEOS (tetraethyl orthosilicate, purity 98%, Sigma-Aldrich) and silver nitrate (Sigma-Aldrich) were used as the main substances, along with the stabilizer PVP (0.01% w / v ratio) and a mixture of 1 mM sodium tetraphenylborate (TPB) solution (polyvinylpyrrolidone, PVPK25, MW = 1300000, purity: 98%) and butanol (solubility: 77 g / L, purity: 99.9%, Merck).

[0151] Doping solution (TEOS+AgNO) with a concentration of 0.1 g (PVP) / mL 3A 100 ml butanol solution was prepared. First, 14 ml butanol and 24 ml TEOS were mixed and stirred well at 80 °C for 30 min. Then, 4 grams of PVP was added to the mixture and mixing was continued at 120 °C for 90 min. After that, the resulting solution was kept under ambient conditions for 24 h to relax the polymer chains. The viscosity and conductivity of the solution were evaluated to obtain suitable rheological properties for the electrospinning process.

[0152] Nickel, tetraphenylborate, PVP, and SiO 2 Nanofibers containing

[0153] To prepare the dope solution, TEOS (tetraethyl orthosilicate, purity 98%, Sigma Aldrich) and nickel II acetate (NiAc) (Sigma-Aldrich) were used as the main substances, along with the stabilizer PVP (0.01% w / v ratio) and a mixture of 1 mM sodium tetraphenylborate (TPB) solution (polyvinylpyrrolidone, PVPK25, MW = 1300000, purity: 98%) and butanol (solubility: 77 g / liter, purity: 99.9%, Merck).

[0154] A dope solution (TEOS+NiAc+butanol) with a concentration of 0.1 g(PVP) / mL was prepared. First, 14 ml of butanol and 24 ml of TEOS+nickel acetate were mixed and stirred well at 80°C for 30 min.

[0155] Then, 4 grams of PVP was added to the mixture and mixing was continued at 120° C. for 90 minutes.

[0156] The resulting solution was then kept under ambient conditions for 24 h to relax the polymer chains. The viscosity and conductivity of the solution were evaluated to obtain suitable rheological properties for the electrospinning process.

[0157] Example 4: Nanofiber Stability

[0158] Elemental analysis was performed to examine the possible leaching of metal ions in blood or water samples.

[0159] To investigate the stability of the nanoconjugates, microwave plasma atomic emission spectroscopy (MP-AES) analysis was performed. For sample preparation, the nanofibers were kept in water at pH 5 for 24 h. After 24 h, the water samples were subjected to MP-AES analysis. This was repeated at pH 7.2 and pH 8.8. The experimental setup is shown in Table 5A (silver) and Table 5B (nickel).

[0160] The results in Table 6A (silver) and Table 6B (nickel) show that no leaching of metal ions was observed at pH 5, pH 7.2, and pH 8.8. See Table 6 below.

[0161] [Table 5A]

[0162] [Table 5B]

[0163] [Table 6A]

[0164] [Table 6B]

[0165] Microwave plasma atomic emission spectroscopy (MP-AES) analysis was performed to investigate the stability period of the nanoconjugates and their stability in blood. For sample preparation, silver or cobalt nanofibers were kept in blood at pH 7 for 12 or 24 h. After 12 or 24 h, water samples were subjected to MP-AES analysis. The experimental setup is shown in Table 7A (silver) and Table 7B (cobalt).

[0166] [Table 7A]

[0167] [Table 7B]

[0168] In further studies, nickel and cobalt nanofibers were independently placed in blood at pH 7 for 12 and 24 hours, respectively. Blood samples were then subjected to MP-AES analysis. No leaching of metals into the samples was observed (example data shown in Table 8). The data demonstrated the stability time (12 and 24 hours) of the nanofibers and their stability when exposed to blood.

[0169] [Table 8A]

[0170] [Table 8B]

[0171] The nickel nanofibers were analyzed by XRD and two sharp peaks of nickel nanoparticles were found (see Figure 9). The intensity is determined in the range of 20°<2θ<90° with a step size of 0.02 degrees. The 2θ values ​​are found to be 37.7922° and 43.8231°, respectively. The peak with the highest intensity, 43.8231°, was used to estimate the crystallite size. The 2θ peaks are 37.7922 and 43.8231. The specific diffraction peaks correspond to the fcc structure (Nickel, syn, JCPDS card no. 04-0850) (Data from ICDD / JCPDS PDF Retrievals [Level-1 PDF, Set 1-51]) (Wei Ni, et al. 2014). It is important to note that only the fcc phase of Ni is present.

[0172] The cobalt nanofibers were analyzed by XRD (Figure 10). The diffractions obtained at 2θ = 41.87° and 51.79° were for the (111) and (200) planes, respectively, indicating the fcc phase of the cobalt spheres (fcc, ICDD / JCPDS No.15-806) (Qiying Liu et.al.,2015).

[0173] Example 5: Prototype Preparation

[0174] Pre-prototype work

[0175] Effective area: approx. 0.8cm 2 A small device (syringe filter) was fabricated using a membrane composed of nanofibers A and B as described above with a nanofiber loading of approximately 0.2 mg.

[0176] The contact time of the urea solution with the device was increased to about 40 seconds to filter 0.6 mL of urea solution, and the filtrate contained no urea. An additional 0.6 mL of urea solution (25 μg / 0.6 ml) was passed through the device (and onto the nanofibers), and the urea in the filtrate was measured each time. The membrane could be regenerated by passing 0.1 M NaOH and rinsing with water, allowing at least one cycle of urea oxidation as described above.

[0177] Prototype design and optimization

[0178] Two nanofiber compositions were tested and found to be effective in removing urea and ammonia from blood via hemodialysis.

[0179] Nanofiber A and nanofiber B were tested separately in two different cartridges.

[0180] Nanofiber A contained 50 μg of nickel (0.1 μg / ml) and 150 μg of silver (0.3 μg / ml) for urea removal and 25 μg of silicon dioxide (0.05 μg / ml) for ammonia removal.

[0181] Nanofiber B contained 25 μg of cobalt (0.05 μg / ml) and 150 μg of silver (0.3 μg / ml) for urea removal, and 25 μg of tetraphenylborate (0.05 μg / ml) and 50 μg of silicon dioxide (0.1 μg / ml) for ammonia removal.

[0182] Add nanofibers (ratio A:B = 90:10) to the cartridge (housing) and add 1.4m 2 of surface area (exposed to blood for urea removal) was obtained. The amount of nanoparticles depended on the size of the cartridge.

[0183] The prototype was designed by a third-party designer with 3D prototyping according to the requirements in Table 9 and the EBPG guideline on dialysis strategies published in 2007 (Nephrology Dialysis Transplantation, Volume 22, Issue suppl_2, May 2007, Pages ii5-ii21, https: / / doi.org / 10.1093 / ndt / gfm022). Acrylonitrile butadiene styrene (ABS) was selected for the construction of the outer case. The 3D prototype was printed with a 3D printer. The nanofibers were inserted vertically into the prototype by hand. The prototype was covered with a cap. The dimensions of the prototype are shown in Table 9 below, and the CAD drawings are shown in Figures 12A and 12B.

[0184] [Table 9]

[0185] dialysis machine

[0186] The same diameter tubing was used for the inflow and outflow to the cartridge. The cartridge was installed in a Nikkiso dialysis machine and no leaks were observed.

[0187] Flow Optimization

[0188] Water (pH 7.0) was used for the initial analysis of the prototype. Water was stored in one container that acted as a reservoir. The following procedure was performed: The prototype was connected to a hemodialysis machine, a single cartridge was used as the prototype and the flow rate was adjusted to 100 ml / min (for 20 minutes). The prototype was analyzed for leakage, reflux and stability. This procedure was repeated at 200 ml / min and 300 ml / min. No leakage of solvent through the dialyzer was observed at 100, 200 and 300 ml / min. No leaching was observed at 100, 200 and 300 ml / min. Inflow and outflow remained stable during the extensive testing.

[0189] The prototype was used as a dialyzer for urea reduction experiments.

[0190] Urea reduction and flow optimization

[0191] A urea solution was prepared (70 mg / dl). The urea solution was stored in one container, which served as the urea reservoir. The flow rate was adjusted to 100 ml / min (for 10 and 20 min). The urea solution was passed through the dialyzer prototype. First, a sample was taken from the outer end for analysis at 0 min after the urea solution had passed through the prototype. Samples were taken at 10 and 20 min after the nanofibers were exposed to the dialyzer. The urea concentration was estimated. The results are shown in Table 10. The flow rate was adjusted on the control panel of the hemodialysis machine. The control, referred to as "standard", was a commercially available urea dialysis cartridge (Nikkiso) (Japan).

[0192] [Table 10]

[0193] The flow rate of the hemodialyzer was adjusted to 100 ml / min. Urea was estimated with an ELISA reader. The first pass of the urea solution through the dialyzer was taken as the zero time sample. This sample was taken within 1 minute. Urea was 17.5 mg / dl compared to 40 mg / dl for the untreated urea solution. (See top and bottom panels of Table 10). Urea concentration 10 minutes after passing through the dialyzer was 9.23 mg / dl. Urea concentration 20 minutes after passing through the dialyzer was 1.40 mg / dl. (See top and bottom rows of Table 10).

[0194] The flow rate of the hemodialysis machine was adjusted to 200 ml / min. Urea was 16.98 mg / dl compared to the untreated urea solution (40 mg / dl) (see the second and bottom rows of Table 10 - standard commercial dialyzer cartridge). Urea concentration after 10 minutes through the dialyzer was 8.99 mg / dl. Urea concentration after 20 minutes through the dialyzer was 0.91 mg / dl.

[0195] The flow rate of the hemodialysis machine was adjusted to 300 ml / min. The urea was 16.44 mg / dl compared to the untreated urea solution (40 mg / dl) (see row 3 and bottom of Table 10 - standard commercial dialyzer cartridge). The urea concentration after 10 minutes of passing through the dialyzer was 8.74 mg / dl. The urea concentration after 20 minutes of passing through the dialyzer was 0.69 mg / dl.

[0196] The cells were analyzed after passing through the dialyzer. As shown in Figure 11, after 60 minutes of dialysis at 200 ml / min and 300 ml / min, no damaged cells were observed under a microscope.

[0197] Advantages of the urea removal cartridge described herein include, but are not limited to: a) reduction in treatment time from 3-4 hours to 1 hour; b) reduction in dialysis costs due to increased throughput per machine; c) reduction in patient morbidity costs due to elimination of lost revenue due to treatment time; d) cartridge is designed to achieve nearly 70% reduction in urea in a single pass; e) designed to replace current dialyzer cartridges used in hemodialysis; f) cartridge stability (leak-proof) - elemental analysis considering possible leaching of nanoparticle ions in blood or water samples; g) negligible toxicity; h) no leakage of solvent was observed through the dialyzer at different test flow rates; i) no leaching was observed at different test flow rates; j) inflow and outflow were stable during extensive testing; k) in vitro testing of a prototype to degrade urea from a urea solution in 60 minutes.

[0198] Example 6: Preclinical studies in rabbits

[0199] [Table 11]

[0200] Rabbit's medical history: At the first visit, the physical examination was normal. Rectal temperature was 37.5°C, heart rate was 92 beats / min, and respiratory rate was 18 breaths / min. The rabbit was in good physical condition, well hydrated, and docile and alert. The rabbit was intraperitoneally injected with a single dose of cisplatin (6.5 mg / kg). Three days after cisplatin injection, abnormalities were detected, including elevated blood urea nitrogen (BUN) (58.7 mg / dl, reference range 10-33 mg / dl) and elevated serum creatinine (4.3 mg / dl, reference range 0.5-2.2 mg / dl). Samples were then taken for complete blood count (CBC) and serum biochemistry analysis. (Predialysis)

[0201] Surgical procedure

[0202] Anesthesia: Rabbits were inserted into the left marginal ear vein with a 22-gauge (G) catheter and sedated with the following anesthetics: To minimize pain, the ear margin was pretreated with anesthetic cream 1 h before catheterization of the vein. The area was then aseptically clipped and draped. After intubation, rabbits were supplied with a mixture of air and pure oxygen (4–7.5%) at a rate of 40 breaths per minute.

[0203] [Table 12]

[0204] Venous Access: A temporary dialysis catheter was placed as follows: The vessel was cannulated with a 20G over-the-needle catheter using a cut-down technique. A guidewire was passed through the bore of the 20G needle, which was then withdrawn. A dilator sheath was inserted into the vessel over the guidewire, and the guidewire was withdrawn. The catheter was inserted into the vessel through the dilator sheath, the sheath was withdrawn, and the catheter was sutured in place. A lateral thoracic radiograph was taken to confirm that the catheter was properly placed, with the tip at the level of the right atrium. The catheter was sterile wrapped and used only for hemodialysis. The catheter was locked with heparin (500 units) to prevent clotting.

[0205] Hemodialysis: The hemodialysis machine was primed with normal saline (flow rate = 300 ml / min). The dialysis catheter tubing was connected from the rabbit to the dialyzer. Blood was drawn from one of the two ports of the dialysis catheter and was drawn (pre-pump) and then pushed (post-pump) through the extracorporeal circuit by clockwise rotation of the blood pump. Blood then entered the dialyzer and flowed the entire length of the dialyzer. Filtered blood was returned to the rabbit through the second port of the dialysis catheter. Blood flow rate was kept at 5 ml / min for the first 15 minutes and increased to 15 ml / min during dialysis. Blood pressure was continuously monitored.

[0206] Blood toxicity tests: Blood samples were taken at different time points and sent for CBC and biochemistry analysis.

[0207] The results are shown below.

[0208] [Table 13]

[0209] [Table 14]

[0210] Urea estimation from blood demonstrated a reduction in urea levels from 58.7 mg / dl to 27.3 mg / dl within 60 minutes, demonstrating that the nanofiber composition herein can reduce urea by 31.4 mg / dl.

[0211] Example 7: Preclinical studies in dogs

[0212] [Table 15]

[0213] Dog's medical history: On initial visit, physical examination was unremarkable. Rectal temperature was 37.5°C, heart rate 95 beats / min, and respiratory rate 16 breaths / min. The dog was in good condition, well hydrated, and docile and alert. Thoracic auscultation revealed normal lung sounds in all regions. Abdominal palpation was normal. Abnormalities associated with canine renal disease were detected, including elevated blood urea nitrogen (BUN) (64 mg / dl, reference range 6-25 mg / dl) and elevated serum creatinine (2.65 mg / dl, reference range 0.5-1.6 mg / dl). Mean arterial blood pressure was 100 mmHg. Based on the short-term symptoms, including significant azotemia, a diagnosis of acute renal failure (ARF) was suspected. After physical examination, samples were taken for a complete blood count (CBC) and serum biochemistry analysis.

[0214] Surgical procedure

[0215] Anesthesia: Dogs were sedated with the anesthetics listed in the table below, after which the area was clipped and draped in a sterile manner.

[0216] [Table 16]

[0217] Venous Access: A temporary dialysis catheter was placed as follows: The vessel was cannulated with a 16G over-the-needle catheter using a cut-down technique. A guidewire was passed through the lumen of the 16G needle, which was then withdrawn. A dilator sheath was inserted into the vessel over the guidewire, and the guidewire was withdrawn. The catheter was inserted into the vessel through the dilator sheath, the sheath was withdrawn, and the catheter was sutured in place. A lateral thoracic radiograph was taken to confirm that the catheter was properly placed, with the tip at the level of the right atrium. The catheter was sterilely wrapped and used only for hemodialysis. The catheter was locked with heparin (500 units) to prevent clotting.

[0218] Hemodialysis: The hemodialysis machine was primed with normal saline (flow rate = 300 ml / min). The dialysis catheter tubing was connected from the dog and attached to the dialyzer. Blood was drawn from one of two ports of the dialysis catheter and was drawn (pre-pump) and then pushed (post-pump) through the extracorporeal circuit by clockwise rotation of the blood pump. Blood then entered the dialyzer and flowed the entire length of the dialyzer. Filtered blood was returned to the dog through the second port of the dialysis catheter. Blood flow rate was kept at 5 ml / min for the first 15 minutes and increased to 20 ml / min during dialysis. Blood pressure was continuously monitored.

[0219] Blood Toxicity Tests. Blood samples were taken at different time points and sent for analysis.

[0220] The results are shown below.

[0221] [Table 17]

[0222] [Table 18]

Claims

1. A nanofiber composition comprising a polymer and nanoparticles comprising one or more of nickel, cobalt, silver, and tetraphenylborate.

2. 10. The composition of claim 1, wherein the polymer comprises one or more of silicon dioxide, polyurethane prepolymer (PUP), polylactic acid (PLA), polycarbonate, polyvinyl alcohol (PVA), polyacrylic acid (PAA), polyethylene glycol (PEG), and polyvinylpyrrolidone (PVP).

3. 10. The nanofiber composition of claim 1, wherein the nanoparticles comprise nickel.

4. 10. The nanofiber composition of claim 1, wherein the nanoparticles comprise cobalt.

5. The nanofiber composition of claim 1 , wherein the nanoparticles comprise silver.

6. The nanofiber composition of claim 1 , wherein the nanoparticles comprise tetraphenylborate.

7. The composition of claim 1 , wherein the nanofiber composition comprises nickel nanoparticles and cobalt nanoparticles.

8. The composition of claim 1 , wherein the nanofiber composition comprises nickel nanoparticles and silver nanoparticles.

9. The composition of claim 1 , wherein the nanofiber composition comprises cobalt nanoparticles and silver nanoparticles.

10. The composition of claim 1 , wherein the nanofiber composition comprises nickel nanoparticles, cobalt nanoparticles, silver nanoparticles, and tetraphenylborate nanoparticles.

11. 10. The composition of claim 1, wherein the polymer comprises silicon dioxide and the nanoparticles comprise nickel and cobalt.

12. The composition of claim 1 , wherein the polymer comprises silicon dioxide and the nanoparticles comprise silver and cobalt.

13. The composition of claim 11 , wherein the polymer further comprises polyvinylpyrrolidone (PVP).

14. 12. The composition of claim 11, further comprising tetraphenylborate nanoparticles.

15. A cartridge comprising one or more membranes, each membrane comprising a nanofiber composition, the nanofiber composition comprising a polymer and one or more nanoparticles comprising nickel, cobalt, silver, and / or tetraphenylborate.

16. a. a filtering chamber configured to receive blood containing urea; b. one or more membranes disposed within the filtration chamber; An apparatus comprising: each membrane comprises nanofibers comprising a polymer and nanoparticles comprising one or more of nickel, cobalt, silver, and tetraphenylborate; the nanofibers are capable of binding urea, converting urea to ammonia, and then binding ammonia; The device.

17. 1. A method for reducing urea concentration from blood, comprising: a. providing blood containing urea to a device containing a cartridge, the cartridge containing one or more membranes, each membrane containing the nanofiber composition of claim 1; b. contacting the blood with the membrane for an amount of time sufficient to allow binding of urea and conversion of urea to ammonia; c. pumping the blood through the cartridge at a pressure sufficient to allow binding of ammonia to the membrane, thereby reducing the concentration of urea in the blood; The method comprising:

18. 1. A method of treating a subject having a disease state characterized by elevated blood urea levels, comprising: a. obtaining a blood sample from said subject; b. pumping the sample through the nanofiber composition of claim 1 for a time sufficient to allow the nanofiber composition to bind urea, convert the urea to ammonia, and then bind the ammonia, thereby creating a filtered blood sample; c. returning the filtered blood sample to the subject, thereby treating the subject; The method comprising:

19. 1. A method of treating a mammal for elevated blood urea levels, comprising: a. providing blood containing urea to a device comprising one or more membranes, each membrane comprising the nanofiber composition of claim 1, wherein the nanofibers are capable of binding urea, converting the urea to ammonia, and then binding the ammonia; b. contacting the blood with the membrane for an amount of time sufficient to allow binding of urea and conversion to ammonia; c. pumping the blood through the cartridge at a pressure and flow rate sufficient to allow binding of ammonia to the nanofibers, thereby reducing the concentration of urea in the blood; The method comprising:

20. 1. A method of treating a subject having a disease state characterized by elevated blood urea levels, comprising: a) subjecting the subject to extracorporeal hemofiltration, wherein blood is drawn from the subject and filtered through a device comprising a filtration chamber (1) configured to receive blood having an elevated urea concentration and (2) comprised of one or more membranes, each membrane comprising the nanofiber composition of claim 1; b. incubating the blood or plasma with the one or more membranes for a time sufficient to allow binding of urea to the nanofibers, conversion of urea to ammonia, and subsequent binding of ammonia to the nanofibers; c) pumping the blood through the device at a pressure and flow rate sufficient to filter the blood and produce a volume of filtered blood; d. returning the filtered blood, which has had its urea concentration reduced by at least 50%, to the subject; The method comprising:

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