Intravesical delivery system

Abstract

A delivery system for chemotherapy, biologics, and / or drugs includes a series of implantable beads, each bead of the series of implantable beads having a bead core through which a central channel passes. The bead core contains one or more of a chemotherapy agent, a biologic, and a drug. The delivery system further includes a wire configured for guiding each bead, individually or as a group held together by a water-soluble coating, into a target organ, the wire passing through the central channel of each bead while each of the series of implantable beads is positioned in its entirety in the target organ via the wire. The target organ includes a bladder, a ureter, or a kidney. The chemotherapy agent, biologic, and drug include a chemotherapy powder that is effective for treating cancer mixed with a dissolvable compound. Cancer includes urothelial cancer or bladder cancer.

Description

INTRAVESICAL DELIVERY SYSTEMCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit under 35 U.S.C. §119(e) of U.S. provisional patent application No. 63 / 615,115, filed December 27, 2023, the entirety of which is hereby incorporated by reference.FIELD OF INVENTION

[0002] This invention relates generally to a delivery system used for delivery of chemotherapy, biologies, and / or drugs, and, more specifically to a delivery system using a series of beads for releasing one or more of a chemotherapy drug, biologies, and drugs into a target organ.BACKGROUND

[0003] All publications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.

[0004] Urothelial cancer is one of the most common malignancy in men and has the distinction of being the cancer with the highest treatment cost of any condition. The vast majority or about 80% of patients with localized disease within the bladder can be managed with local therapies. Recent clinical studies have demonstrated that the instillation of chemotherapy into the bladder can be an effective means to treat bladder cancer.

[0005] For example, intravesical therapy is used for some bladder cancers. With intravesical therapy, a liquid drug is put right into the bladder rather than being given by mouth or injected into the blood. The drug is given through a tube or urinary catheter put into the bladder through the urethra. Thus, drugs given directly into the bladder affect the cells lining the inside of the bladder and have little to no effect on cells elsewhere. Therefore, any cancer cells outside of the bladder lining, including those that have grown deeply into the bladder wall, are not treated by intravesical therapy. Drugs put into the bladder also cannot reach any cancer cells in other parts of the body.

[0006] However, current protocols rely on regular and repeated catheter placement and chemotherapy instillation into the bladder. For example, existing solution is to have the patient return to clinic 1-3 times a week for a catheter to be placed, and then chemotherapy instilled into the bladder for 1-2 hours. This process can be time consuming, expensive, uncomfortable for patients and may result in inconsistent delivery of the drug to the bladder.

[0007] Therefore, there is a great need in the art for intravesical chemotherapy that is effective to treat bladder cancer. Further, there is a need for an easier, safer, and more convenient delivery mechanism that allows for extended duration of chemotherapy within the bladder without requiring a trip to the operating room. The present disclosure is directed to solving these and other problems.SUMMARY

[0008] Described herein is a urinary foley which has a central channel adapted for the delivery of chemotherapy (or other water-soluble drugs) into a hallow organ by releasing a series of drug eluting beads. In particular, the delivery mechanism uses the implantation of a flexible tube into an organ cavity such as the renal collecting system which is filled with chemotherapy to allow for gradual release of chemotherapy into the urine. In some embodiments, the delivery mechanism includes a specialized delivery system allowing for drug releasing device placement within the bladder and / or kidney and designs for the chemotherapy releasing device. For example, the delivery mechanism uses the implantation of a flexible tube into the bladder or the kidney which is filled with chemotherapy to allow for gradual release of chemotherapy into the bladder.

[0009] According to various embodiments of the present invention, a delivery system includes a series of implantable beads, each bead of the series of implantable beads having a bead core through which a central channel passes, the bead core containing one or more of a chemotherapy agent, a biologic, and a drug mixed with a dissolvable compound; and a wire configured for guiding each bead, individually or as a group held together by a water soluble coating, into a target organ, the wire passing through the central channel of each bead while the series of implantable beads is positioned in its entirety in the target organ via the wire.

[0010] In some embodiments, the series of implantable beads is held together with a coating on an exterior surface of the bead core.

[0011] In some embodiments, the coating is a soluble biocompatible coating.

[0012] In some embodiments, the dissolvable biocompatible coating is urine-soluble or water-soluble.

[0013] In some embodiments, the soluble biocompatible coating includes polyethyleneglycol (PEG), polyvinyl alcohol (PVA), Xanatham gum, cellulose ethers, or Biodegradable polyphosphoesters (PPE).

[0014] In some embodiments, when the series of implantable beads is delivered into the target organ, the soluble biocompatible coating is dissolved prior to dissolving of the series of implantable beads.

[0015] In some embodiments, the target organ is a kidney, and the soluble biocompatible coating and the series of implantable beads are dissolved in the kidney.

[0016] In some embodiments, when the series of implantable beads is delivered into the target organ, the soluble biocompatible coating is dissolved after dissolving of the series of implantable beads.

[0017] In some embodiments, the target organ is a bladder, and the soluble biocompatible coating and the series of implantable beads are dissolved in the bladder.

[0018] In some embodiments, the soluble biocompatible coating is dissolved such that each bead is separated from the series of implantable beads and is dispersed individually in the target organ, each bead, subsequently, dissolving to release the one or more of the chemotherapy agent, biologic, and drug over time.

[0019] In some embodiments, the one or more of the chemotherapy agent, biologic, and drug is released for at least 4 weeks subsequent to separation of each bead from the series of implantable beads.

[0020] In some embodiments, the delivery system further includes a urinary catheter having a central channel and configured to deliver the wire and the series of implantable beads within the target organ.

[0021] In some embodiments, each bead is elongated to have a cylindrical shape.

[0022] In some embodiments, the series of implantable beads are severable to form at least one sub-series of implantable chemotherapy beads.

[0023] In some embodiments, each bead is impregnated with a radiopaque material.

[0024] In some embodiments, the radiopaque material is visible on X-ray.

[0025] In some embodiments, the dissolvable compound is a water dissolvable compound that includes a non-biological sugar.

[0026] In some embodiments, the target organ is a bladder, a ureter, or a kidney.

[0027] In some embodiments, the bead core contains the same chemotherapy agent, biologic, or drug.

[0028] In some embodiments, all of the series of implantable beads contain the same chemotherapy agent, biologic, or drug.

[0029] In some embodiments, the series of implantable beads contain at least two different types of beads, each type of beads containing a different chemotherapy agent, biologic, or drug.

[0030] In some embodiments, the series of implantable beads includes a first group of implantable beads containing a chemotherapy agent and a second group of implantable beads containing one or more of a biologic and a drug.

[0031] In some embodiments, each of the first group and the second group is a half or about a half of the series of implantable beads.

[0032] In some embodiments, the series of implantable beads includes a first group of implantable beads containing a chemotherapy drug and a second group of implantable beads containing an antineoplastic agent.

[0033] In some embodiments, the chemotherapy drug comprises gemcitabine.

[0034] In some embodiments, the antineoplastic agent comprises docetaxel.

[0035] In some embodiments, the one or more of the chemotherapy agent, biologic, and drug is effective for treating cancer.

[0036] In some embodiments, the cancer includes urothelial cancer or bladder cancer.

[0037] According to various embodiments of the present invention, a method of administering a drug to a patient in need thereof includes: inserting a wire through the patient's urethra and bladder and into the patient's ureter; placing a series of implantable beads over the wire and advancing the series of implantable beads into the patient’s kidney by pushing a stent loaded over the wire, each bead of the series of implantable beads containing one or more of a chemotherapy agent, a biologic, and a drug; deploying the stent within the patient’s ureter; and allowing each bead in the patient’s kidney to slowly elute the one or more of the chemotherapy agent, biologic, and drug out of each bead into the patient’s renal collecting system, ureter, and bladder. Each bead has a bead core through which a central channel passes, the wire passing through the central channel of each bead while the series of implantable beads is positioned in its entirety in the kidney via the wire.

[0038] In some embodiments, the method further includes inserting a urinary catheter having a central channel such that the wire and the series of implantable beads are passed up the ureter through the central channel of the urinary catheter and delivered within the patient’s kidney.

[0039] In some embodiments, the method further includes placing a cystoscope in the patient’s bladder by inserting the cystoscope into the patient’s urethra such that the wire and the series of implantable beads are passed up the patient’s ureter through the cystoscope.

[0040] In some embodiments, each bead of the series of implantable beads is elongated to have a cylindrical shape.

[0041] In some embodiments, the implantable beads are chained.

[0042] In some embodiments, the chained implantable beads or the series of implantable beads is severable to form at least one sub-series of implantable beads.

[0043] In some embodiments, the series of implantable beads are held together with a coating on an exterior surface of the bead core.

[0044] In some embodiments, the coating is a soluble biocompatible coating.

[0045] In some embodiments, the dissolvable biocompatible coating is urine-soluble or water-soluble.

[0046] In some embodiments, the soluble biocompatible coating includes polyethylene glycol (PEG), polyvinyl alcohol (PVA), Xanatham gum, cellulose ethers, or Biodegradable polyphosphoesters (PPE).

[0047] In some embodiments, when the series of implantable beads is delivered into the patient’s kidney, the soluble biocompatible coating is dissolved prior to dissolving of the series of implantable beads.

[0048] In some embodiments, the soluble biocompatible coating is dissolved such that each bead is separated from the series of implantable beads and is dispersed individually in the patient’s kidney, each bead, subsequently, dissolving to release the one or more of the chemotherapy agent, biologic, and drug over time.

[0049] In some embodiments, the one or more of the chemotherapy agent, biologic, and drug is released for at least 4 weeks subsequent to separation of each bead from the series of implantable beads.

[0050] In some embodiments, each bead is impregnated with a radiopaque material visible on X-ray such that the beads are trackable.

[0051] In some embodiments, the one or more of the chemotherapy agent, biologic, and drug is effective for treating cancer including urothelial cancer or bladder cancer.

[0052] In some embodiments, the stent is left in the patient’s ureter to prevent the beads from passing from the patient’s kidney as the beads dissolve.

[0053] In some embodiments, the one or more of chemotherapy agent, biologic, and drug includes a chemotherapy powder mixed with a dissolvable compound.

[0054] In some embodiments, the dissolvable compound is a water dissolvable compound that includes a non-biological sugar.

[0055] In some embodiments, the series of implantable beads contain a same chemotherapy agent, biologic, or drug.

[0056] In some embodiments, the series of implantable beads include a first group ofimplantable beads and a second group of implantable beads, implantable beads of the first group and implantable beads of the second group containing a different chemotherapy agent, biologic, or drug.

[0057] In some embodiments, the first group contains a chemotherapy agent and the second group contains one or more of a biologic and a drug.

[0058] In some embodiments, the first group contains a chemotherapy drug and the second group contains an antineoplastic agent.

[0059] In some embodiments, the chemotherapy drug comprises gemcitabine.

[0060] In some embodiments, the antineoplastic agent comprises docetaxel.

[0061] According to various embodiments of the present invention, a method of administering one or more of a chemotherapy agent, a biologic, and a drug to a patient in need thereof includes: inserting a wire through a nephrostomy tube into the patient's kidney; placing a series of implantable beads over the wire and advancing the series of implantable beads into the patient’s kidney over the wire by using a pushing tool, each bead of the series of implantable beads containing the one or more of the chemotherapy agent, biologic, and drug; removing the wire from the nephrostomy tube; and allowing the beads in the patient’s kidney to slowly elute the one or more of the chemotherapy agent, biologic, and drug out of the beads into the patient’s renal collecting system, ureter, and bladder. Each bead of the series of implantable beads has a bead core through which a central channel passes, the wire passing through the central channel of each bead while the series of implantable beads is positioned in its entirety in the patient’s kidney via the wire.

[0062] In some embodiments, each bead of the series of implantable beads is elongated to have a cylindrical shape.

[0063] In some embodiments, the implantable beads are chained.

[0064] In some embodiments, the chained plurality of beads or the series of implantable beads is severable to form at least one sub-series of implantable beads.

[0065] In some embodiments, the series of implantable beads is held together with a coating on an exterior surface of the bead core.

[0066] In some embodiments, the coating is a soluble biocompatible coating.

[0067] In some embodiments, the dissolvable biocompatible coating is urine-soluble or water-soluble.

[0068] In some embodiments, the urine or water-soluble biocompatible coating comprises polyethylene glycol (PEG), polyvinyl alcohol (PVA), Xanatham gum, cellulose ethers, or Biodegradable polyphosphoesters (PPE).

[0069] In some embodiments, when the series of implantable beads is delivered into the patient’s kidney, the soluble biocompatible coating is dissolved prior to dissolving of the series of implantable beads.

[0070] In some embodiments, the soluble biocompatible coating is dissolved such that each bead is separated from the series of implantable beads and is dispersed individually in the patient’s kidney, each bead, subsequently, dissolving to release the one or more of the chemotherapy agent, biologic, and drug over time.

[0071] In some embodiments, the one or more of the chemotherapy agent, biologic, and drug is released for at least 4 weeks subsequent to separation of each bead from the series of implantable beads.

[0072] In some embodiments, each bead is impregnated with a radiopaque material visible on X-ray such that the beads are trackable.

[0073] In some embodiments, the one or more of the chemotherapy agent, biologic, and drug is effective for treating cancer including urothelial cancer or bladder cancer.

[0074] In some embodiments, a dosage of the one or more of the chemotherapy agent, biologic, and drug is controlled by advancing a target number of beads corresponding to the dosage over the wire into the patient’s kidney.

[0075] In some embodiments, the method further includes placing the nephrostomy tube into the kidney.

[0076] In some embodiments, the one or more of the chemotherapy agent, biologic, and drug includes a chemotherapy powder mixed with a dissolvable compound.

[0077] In some embodiments, the dissolvable compound is a water dissolvable compound that includes a non-biological sugar.

[0078] According to various embodiments of the present invention, a series of implantable chemotherapy beads is disclosed. Each chemotherapy bead of the series of implantable chemotherapy beads has a bead core through which a central channel passes, the bead core containing a chemotherapy powder mixed with a dissolvable compound; each chemotherapy bead is elongated to have a cylindrical shape; the series of implantable chemotherapy beads is severable; the series of implantable chemotherapy beads is held together with a urine or water- soluble biocompatible coating; and / or each chemotherapy bead is impregnated with a radiopaque material visible on X-ray.

[0079] In some embodiments, each chemotherapy bead includes one or more of a chemotherapy agent, biologic, and drug for treating cancer comprising urothelial cancer or bladder cancer.

[0080] In some embodiments, the series of implantable chemotherapy beads is movable via a wire passing through the central channel of each chemotherapy bead and is implantable in a patient’s kidney for prolonged release of the one or more of the chemotherapy agent, biologic, and drug into the patient’s renal collecting system, ureter, and bladder.

[0081] In some embodiments, the soluble biocompatible coating is dissolved prior to dissolving of the series of implantable chemotherapy beads, and the one or more of the chemotherapy agent, biologic, and drug is released for at least 4 weeks subsequent to separation of each chemotherapy bead from the series of implantable chemotherapy beads.

[0082] According to various embodiments of the present invention, a delivery system is disclosed. The delivery system includes a series of implantable beads, each bead of the series of implantable beads containing one or more of a chemotherapy agent, a biologic, and a drug mixed with a dissolvable compound. The delivery system further includes a tube configured for guiding each bead, individually or as a group held together by a water-soluble coating, into a target organ. The delivery system further includes a plunger configured for pressing the series of implantable beads into the tube and pressing the beads through the tube such that the pressed beads are released into the target organ while the series of implantable beads is positioned in in the target organ via the tube.

[0083] According to various embodiments of the present invention, a method of administering one or more of a chemotherapy agent, a biologic, and a drug to a patient in need thereof is disclosed. The method includes inserting a series of implantable beads that are held together by coating into a tube, each bead of the series of implantable beads containing the one or more of the chemotherapy agent, biologic, and drug; inserting the tube containing the series of implantable beads into the patient's organ; advancing the series of implantable beads through the tube into the patient’s organ by pressing the series of implantable beads with a pushing tool or a plunger; and removing the tube from the patient’s organ. The beads in the patient’s organ are allowed to slowly elute the one or more of the chemotherapy agent, biologic, and drug out of the beads into the patient’s organ.

[0084] The above summary is not intended to represent each embodiment or every aspect of the present disclosure. Rather, the foregoing summary merely provides an example of some of the novel aspects and features set forth herein. The above features and advantages, and other features and advantages of the present disclosure, will be readily apparent from the following detailed description of representative embodiments and modes for carrying out the present invention, when taken in connection with the accompanying drawings and the appended claims. Additional aspects of the disclosure will be apparent to those of ordinary skill in the art in view ofthe detailed description of various embodiments, which is made with reference to the drawings, a brief description of which is provided below.BRIEF DESCRIPTION OF THE FIGURES

[0085] Exemplary embodiments are illustrated in referenced figures. It is intended that the embodiments and figures disclosed herein are to be considered illustrative rather than restrictive.

[0086] FIG. 1 A is a perspective view showing a series of implantable beads, in accordance with an exemplary embodiment of the present disclosure.

[0087] FIG. IB illustrates the series of beads shown in FIG. 1A with a coating, in accordance with an aspect of the present disclosure.

[0088] FIG. 1C illustrates a series of implantable solid beads, in accordance with an exemplary embodiment of the present disclosure.

[0089] FIG. 2 is an image showing a cystoscope being inserted into the urethra, in accordance with another aspect of the present disclosure.

[0090] FIG. 3A illustrates an initial step of passing a wire up the ureter through the cystoscope, according to an aspect of the present disclosure.

[0091] FIG. 3B illustrates a next step in placing a series of implantable beads over the wire and advancing the beads into the kidney, by pushing a stent or push bar loaded over the wire, according to another aspect of the present disclosure.

[0092] FIG. 3C illustrates a further step in deploying a double J ureteral stent within the ureter and eluting the drug out of the beads implanted within the kidney, according to yet another aspect of the present disclosure.

[0093] FIG. 4 is a flowchart illustrating a method of administering a drug to a patient, according to an aspect of the present disclosure.

[0094] FIG. 5 is a flowchart illustrating a method of administering a drug to a patient, according to another aspect of the present disclosure.DESCRIPTION OF THE INVENTION

[0095] Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. One skilled in the art will recognize many methods and materials similar or equivalent to those described herein, which could be used in the practice of the present invention. Indeed,the present invention is in no way limited to the methods and materials described. For purposes of the present invention, the following terms are defined below.

[0096] As used herein, the term “intravesical therapy” or “intravesical chemotherapy” refers to treatment by putting chemotherapy (chemo) drugs right into the bladder through a catheter. These drugs kill actively growing cancer cells. For example, the chemotherapy drugs delivered for intravesical chemotherapy are mitomycin, gemcitabine, docetaxel, cisplatin, and several other less commonly used chemotherapeutic agents. Alternatively, other biologically active molecules such as check point inhibitors or small biologic drugs can be implanted into these beads to act as a delivery system.

[0097] Conventional drug delivery systems merely instill chemotherapy drug(s) directly into the bladder for a certain period of time, e.g., 1-2 hours, via a catheter placed into the bladder. Strategies to improve the pharmacological therapy of urinary bladder diseases have been aimed at maintaining effective drug levels in situ through the use of delivery systems able to be retained and release the drug into the organ for a prolonged period of time and / or enhancing permeation of locally administered drugs throughout the bladder wall. The inventive drug delivery systems achieve the above-identified strategies. For example, the drug delivery system / device is used to treat patients with localized bladder cancer or high grade bladder cancer which is currently often treated with intravesical chemotherapy.

[0098] For effective intravesical therapy, a mechanism to allow for extended duration of chemotherapy within the bladder is needed. For example, it is necessary to deliver one or more chemotherapies to the kidney, ureter, and bladder in adequate concentration to maintain therapeutic dosing for at least 4 weeks or a longer period at a time. Such a delivery system would eliminate the need for frequent trips to the clinic or operating room for drug emitting device placement. Effective drug delivery to the kidneys, ureters, and bladder can be achieved by using an upper tract chemotherapy bead delivery system disclosed in the patent application.

[0099] According to various embodiments of the present invention, the upper tract chemotherapy bead delivery system is used to deliver drugs to the kidneys, ureters, and / or bladder. According to various embodiments of the present invention, the upper tract chemotherapy bead delivery system includes a urinary foley or specialized urinary catheter having a central channel that is adapted for delivery of chemotherapy releasing series of beads within the bladder. The upper tract chemotherapy bead delivery system further includes a drug emitting temporary implant.

[0100] Referring to FIG. 1A, the drug emitting temporary implant is a series of implantable chemotherapy beads 100 A formulated with a central channel 110, according to oneembodiment of the present disclosure. The central channel 110 allows the chemotherapy beads 101a, 101b, 101c to be placed over a wire 130 and pushed over the wire 130 up the ureter to the kidney. By chaining multiple chemotherapy beads 101a, 101b, 101c together, the efficiency is increased by allowing numerous beads to be deployed at once.

[0101] Referring to FIG. IB, the drug delivery beads 101a, 101b, 101c are optionally coated. For example, to form a string-like structure, a series of drug delivery / chemotherapy beads 101a, 101b, 101c are held together with a urine or water-soluble biocompatible coating 120 such as polyethylene glycol (PEG), polyvinyl alcohol (PVA), Xanatham gum, cellulose ethers, or Biodegradable polyphosphoesters (PPE). The addition of a dissolvable coating 120 over the beads or solid beads allows for the brittle beads to tolerate the forces required to push these beads into the ureter and the smoothness to allow for these to pass through the ureter without causing damage.

[0102] Referring to FIG. 1C, the drug emitting temporary implant is series of implantable chemotherapy beads 100C that do not have a central channel, contrary to the chemotherapy beads 101a, 101b, 101c exemplified in FIGS. 1A and IB. In some embodiments, the series of implantable chemotherapy beads 100C, including “solid” beads lOld, lOle, and lOlf, is coated similar to the embodiment of the series of implantable beads 100B exemplified in FIG. IB. Therefore, the delivery mechanism of the “solid” beads 101 d, lOle, 10 If not requiring a wire is different from the delivery mechanism of the chemotherapy beads 101a, 101b, 101c shown in FIGS. 1A and IB. In the present disclosure, even if beads are described referring to beads 101a, 101b, 101c having a central channel 110, characteristics of the series of implantable beads 100A, 100B or beads 101a, 101b, 101c and the solid beads lOld, lOle, 10 If are generally same or similar unless the difference, such as absence / presence of a central channel, is specifically mentioned.

[0103] Referring to FIGS. 1 A and IB, a series of implantable beads 100A, 100B is formed with a plurality of implantable beads 101a, 101b, 101c that are chained together. Although the number of the chained beads 101a, 101b, 101c is exemplified as 3 chained beads, the number of the beads is not limited thereto. In some embodiments, the number of the chained beads is less than 3. In some embodiments, the number of the chained beads is more than 3 (i.e., the series of implantable beads 100A, 100B has “n” number of beads). Each drug delivery bead 101a, 101b, 101c has a cylindrical or elongated donut-shape. However, the shape of the bead 101a, 101b, 101c is not limited thereto. For example, in some embodiments, the bead 101a, 101b, 101c has a spherical or ball shape. One or more of the drug delivery beads 101a, 101b, 101c has a central channel 110. In the illustrated embodiment, all of the drug delivery beads 101a, 101b, 101c have a respective central channel 110.

[0104] In some embodiments, the length of each bead 101a, 101b, 101c or each solid bead lOld, lOle, lOlf is 3-4 millimeters (mm), about 3 mm, about 3.5 mm, or about 4 mm. In some embodiments, the circumference of each bead 101a, 101b, 101c is 1.6-2.0 mm, about 1.6 mm, about 1.8 mm, or about 2.0 mm.

[0105] In some embodiments, a wire 130 passes through the central channels 110 of the beads 101a, 101b, 101c. The wire 130 is configured for guiding each bead 101a, 101b, 101c, individually, into a target organ, as further disclosed below. The wire 130 passes through the central channel 110 of each bead 101a, 101b, 101c, while each series of implantable beads 100A, 100B is positioned in its respective entirety in the target organ via the wire 130.

[0106] In some embodiments, the diameter of the central channel 110 is 1-1.2 mm, about 1 mm, about 1.1 mm, or about 1.2 mm. The channel 110 is required for delivering the beads 101a, 101b, 101c by being advanced over the wire 130 passing through the channels of the beads 100A, 100B. The wire 130 is further illustrated in FIGS. 3A-3B.

[0107] In some embodiments, beads 101a, 101b, 101c or solid beads lOld, lOle, lOlf have a smooth contour allowing for them to be advanced up the ureter with limited trauma. For example, the beads 101a, 101b, 101c are free of projections, lumps, or indentations such that surfaces of the beads 101a, 101b, 101c are even and consistent. In some embodiments, the beads 101a, 101b, 101c are impregnated with a radiopaque material to allow for visualization on X-ray. The admixture of a radio-opaque compound into the beads 101a, 101b, 101c allows visualization of the beads with X-ray such that a clinician can assess the location of the beads and estimate current load of drug in the collecting system.

[0108] In some embodiments, the beads 101a, 101b, 101c or solid beads lOld, lOle, lOlf contain chemotherapy powder mixed with a water dissolvable compound like a non-biological sugar. In some embodiments, a head core of each bead 101a, 101b, 101c contains a chemotherapy powder mixed with a dissolvable compound. A central channel 110 passes through the bead core. These beads 101a, 101b, 101c are then strung together by a coating 120 such as polyvinyl alcohol which itself is water dissolvable to form a series of coated implantable beads, as exemplified in FIG. IB.

[0109] In some embodiments, the solid beads 101 d, 101 e, 10 If that do not have a central channel may contain an increased content of therapeutic material within the beads than the beads 101a, 101b, 101c having the central channels 110. Thus, using the solid beads lOld, lOle, lOlf may allow a larger payload delivery of the therapeutic material compared to a payload achieved by the beads 101a, 101b, 101c with the central channel 110.

[0110] In some embodiments, the beads 101a, 101b, 101c or solid beads lOld, lOle, lOlf are held together with a flexible water-soluble material that allows for smooth deployment of beads and deployment of numerous beads at one time.

[0111] In some embodiments, the beads 101a, 101b, 101c are delivered into a target organ of a patient such as the bladder, ureter, and / or kidney by being pushed by a double J ureteral stent advancing over the wire 130. Ureteral stenting (double J ureteral stent) is the procedure to place a thin, flexible plastic tube that is temporarily in the ureter to help urine drain from the kidney into the bladder in the case of a blockage.

[0112] In some embodiments, the solid beads 101 d, 101 e, 10 If are delivered into a target organ of a patient through a tube. The solid beads 101 d, 101 e, 10 If cannot be advanced over a wire because they do not have a central channel. Therefore, the solid beads 101 d, lOle, 10 If are advanced by being pushed by a plunger. In some embodiments, a plurality of solid beads 101 d, lOle, 10 If are coated, as exemplified in FIG. 1C, to make them stick together, and loaded into a tube with a plunger at the back. Then, the tube is inserted into a target organ, and the plunger is pressed to deposit the solid beads into the target organ.

[0113] In some embodiments, when the series of beads 101a, 101b, 101c or solid beads 101 d, lOle, 10 If are delivered to the target organ such as the kidney, the coating 120 on the beads 101a, 101b, 101c or solid beads lOld, lOle, lOlf dissolves, and then the actual beads start to dissolve slowly over time releasing the chemotherapy drug. That is, the coating 120 holding the beads 101a, 101b, 101c or solid beads 101 d, lOle, 10 If together dissolve first, for example soon after being deployed into the kidney, and then, the separated beads 101a, 101b, 101c or solid beadslOld, lOle, lOlf dissolve slowly. This embodiment allows the beads 101a, 101b, 101c or solid beads lOld, lOle, 10 If to sit in the kidney and elute the contents of the beads. Thus, chemotherapy drug is released for extended duration from the beads 101a, 101b, 101c or solid beads 101 d, lOle, 10 If dissolved in the bladder, ureter, and / or kidney.

[0114] In some embodiments, the duration of the chemotherapy drug release may be adjusted by increasing or decreasing the number of beads 101a, 101b, 101c or solid beads lOld, 101 e, 10 If delivered into the target organ of the patient. For example, increasing the number of beads 101a, 101b, 101c or solid beads lOld, lOle, lOlf may prolong the duration of the chemotherapy drug release, and decreasing the number of beads 101a, 101b, 101c or solid beads 101 d, 101 e, 10 If may shorten the duration of the chemotherapy drug release. In some embodiments, the coating 120 is configured to dissolve within about 90 minutes or 90 minutes after being deployed in the target organ. In some embodiments, each bead 101a, 101b, 101c oreach solid bead lOld, lOle, lOlf is configured to dissolve within about 21 days or 21 days after being deployed in the target organ.

[0115] In other embodiments, when the series of beads 101a, 101b, 101c or solid beads 101 d, lOle, 10 If are delivered to the target organ such as the bladder, the coating 120 over the beads 101a, 101b, 101c or solid beads lOld, lOle, lOlf dissolve over a longer period of time than the beads 101a, 101b, 101c or solid beads lOld, lOle, 10 If themselves, allowing for the delivery system to stay in the bladder without falling out until the contents of the beads are fully delivered. That is, the coating 120 holding the beads 101a, 101b, 101c or solid beads lOld, lOle, lOlf together dissolves, following dissolving of the separated beads 101a, 101b, 101c or solid beads 101 d, 101 e, 10 If . Thus, in the bladder, the coating 120 remains largely intact for some time so that the beads 101a, 101b, 101c or solid beads 101 d, lOle, 10 If remain too large to be urinated out of the bladder.

[0116] According to various embodiments of the present invention, a method of delivering chemotherapy drug into the kidney is achieved by placement of implantable chemotherapy beads through urethral access. In some embodiments, the method includes initially placing a cystoscope 200 in the bladder by inserting the cystoscope into the urethra, as shown in FIG. 2. Subsequently, a wire 130 is passed up in the ureter through the cystoscope, as shown in FIG. 3A. Chemotherapy beads 100 A or 100B are placed over the wire 130 and advanced into the kidney by pushing a stent 310, such as a double J ureteral stent or push bar loaded over the wire 130, as shown in FIG. 3B. The chemotherapy beads 100 A or 100B are placed optionally or preferably under X-ray guidance. The chemotherapy -bead deployment is repeated until a target number of beads 101a, 101b, 101c, and / or lOln (n being an integer greater than 0) is placed or desired types of drugs are placed. The stent 310 is deployed within the ureter, as shown in FIG. 3C. Then, the drug eluting beads 100A or 100B in the kidney slowly elute the drug out of the beads 101a, 101b, 101c, and / or lOln into the renal collecting system, ureter, and bladder such that the drug is eluted for a prolonged period of time. For example, the drug is eluted for at least 4 weeks at a time. In some embodiments, the stent is left in the ureter to prevent the beads from passing from the kidney as they dissolve.

[0117] According to various embodiments of the present invention, a method of delivering chemotherapy drug is achieved by percutaneous placement of chemotherapy beads 100A or 100B. In some embodiments, the method includes placing a wire 130 through a nephrostomy tube into the kidney, following nephrostomy tube placement; placing chemotherapy beads 100 A or 100B over the wire 130; pushing the beads 100 A or 100B into the kidney over the wire 130 using a pushing tool 310; and removing the wire 130 from the nephrostomy tube. Then, the drug slowly elutes out of the beads 100 A or 100B into the renal collecting system, ureter, and bladder suchthat the drug is eluted for a prolonged period of time. For example, the drug is eluted for at least 4 weeks at a time.

[0118] According to various embodiments of the present invention, a method of delivering chemotherapy drug is achieved by percutaneous placement of solid beads 101 d, lOle, 10 If shown in FIG. 1C. In some embodiments, the method includes loading a plurality of solid beads lOld, lOle, 10 If into a tube with a plunger. The plurality of solid beads lOld, 101 e, 10 If may be coated to make them stick together. The method further includes inserting the tube containing the solid beads 101 d, lOle, 10 If into a target organ, such as the bladder or kidney; and pressing the plunger to deposit the solid beads 101 d, lOle, 101 f into the target organ. Then, the drug slowly elutes out of the solid beads 101 d, lOle, 101 f into the target organ such that the drug is eluted for a prolonged period of time. For example, the drug is eluted for at least 4 weeks at a time. Compared to the beads 101a, 101b, 101c having a central channel, the payload of the solid beads 101 d, lOle, 10 If may be greater because an increased content of therapeutic material can be contained within the solid beads lOld, lOle, lOlf because solid beads do not lose the space occupied by the central channel 110 as for the beads 101a, 101b, 101c.Chemotherapy Delivery System with Beads Having a Central Channel

[0119] Various embodiments of the present invention provide for a delivery system including a series of implantable beads 100A or 100B, each bead 101a, 101b, 101c of the series of implantable beads having a bead core through which a central channel 110 passes, the bead core containing one or more of a chemotherapy agent, a biologic, and a drug mixed with a dissolvable compound. An example of the chemotherapy agent, biologic, and / or drug is a chemotherapy powder mixed with a dissolvable compound. The delivery system further includes a wire 130 configured for guiding each bead 101a, 101b, 101c, and / or lOln, individually, into a target organ, the wire 130 passing through the central channel 110 of each bead 101a, 101b, 101c, and / or lOln while the series of implantable beads 100A or 100B is positioned in its entirety in the target organ via the wire 130.

[0120] In some embodiments, each bead 101a, 101b, 101c contains the same one or more of the chemotherapy agent, biologic, and drug. In another embodiments, a first group of beads among the series of beads 100 A or 100B contains a first chemotherapy agent, biologic, or drug, and a second group of beads among the series of beads contains a second chemotherapy agent, biologic, or drug that is different from the first chemotherapy agent, biologic, or drug. In still another embodiments, the series of beads 100 A or 100B further includes a third group of beads containing a third chemotherapy agent, biologic, or drug that is different from the first and secondchemotherapy agent, biologic, and / or drug. In some embodiments, the amount of each of the first and second groups and each of the first, second and third groups is equal or similar.

[0121] In some embodiments, a first portion of the series of beads 100 A or 100B contains a chemotherapy agent and a second portion of the series of beads contain one or more of a biologic and a drug. In some embodiments, the series of beads 100 A or 100B includes beads containing a chemotherapy drug and beads containing an antineoplastic agent. In some embodiments, the chemotherapy drug includes or is gemcitabine. In some embodiments, the antineoplastic agent includes or is docetaxel.

[0122] In various embodiments, the series of implantable beads 101a, 101b, 101c are held together with a coating 120 on an exterior surface of the bead core.

[0123] In various embodiments, the coating 120 is a soluble biocompatible coating.

[0124] In various embodiments, the dissolvable biocompatible coating 120 is urinesoluble or water-soluble.

[0125] In various embodiments, the soluble biocompatible coating 120 includes polyethylene glycol (PEG), polyvinyl alcohol (PVA), Xanatham gum, cellulose ethers, or Biodegradable polyphosphoesters (PPE).

[0126] In various embodiments, when the series of implantable beads 100 A or 100B is delivered into the target organ, the soluble biocompatible coating 120 is dissolved prior to dissolving of the series of implantable beads 101a, 101b, 101c.

[0127] In various embodiments, the soluble biocompatible coating 120 is dissolved such that each bead 101a, 101b, 101c is separated from the series of implantable beads 100A or 100B and is dispersed individually in the target organ, each bead 101a, 101b, 101c, subsequently, dissolving to release a chemotherapy drug over time.

[0128] In various embodiments, the chemotherapy drug is released for at least 4 weeks subsequent to separation of each bead 101a, 101b, 101c from the series of implantable beads 100A or 100B.

[0129] In various embodiments, the delivery system further includes a urinary catheter having a central channel and configured to deliver the wire 130 and the series of implantable beads 100 A or 100B within the target organ.

[0130] In various embodiments, each bead 101a, 101b, 101c is elongated to have a cylindrical shape.

[0131] In various embodiments, the series of implantable beads 100A or 100B is severable to form at least one sub-series of implantable beads.

[0132] In various embodiments, each bead 101a, 101b, 101c is impregnated with a radiopaque material.

[0133] In various embodiments, the radiopaque material is visible on X-ray.

[0134] In various embodiments, the dissolvable compound is a water dissolvable compound that includes a non-biological sugar.

[0135] In various embodiments, the target organ is a bladder, a ureter, or a kidney.

[0136] In various embodiments, the chemotherapy powder includes a chemotherapy drug that is effective for treating cancer.Chemotherapy Delivery System with Beads That Do Not Have a Central Channel

[0137] Various embodiments of the present invention provide for a delivery system including a series of implantable solid beads 101 d, 101 e, 101 f. Contrary to the beads 100 A or 100B exemplified in FIGS. 1A and IB, the solid beads 101 d, lOle, 10 If exemplified in FIG. 1C do not have a central channel. The solid beads 101 d, 101 e, lOlf contain one or more of a chemotherapy agent, a biologic, and a drug mixed with a dissolvable compound. An example of the chemotherapy agent, biologic, and / or drug is a chemotherapy powder mixed with a dissolvable compound. The delivery system further includes a tube into which solid beads 101 d, 101 e, 10 If are loaded. The solid beads 101 d, 101 e, 101 f may be coated to make them stick together. The solid beads lOld, lOle, lOlf may be loaded into the tube with a plunger. The tube is configured for guiding each solid bead lOld, lOle, lOlf individually into a target organ while the series of implantable solid beads 101 d, lOle, 10 If is positioned in the target organ via the tube. Each solid bead 101 d, 101 e, 101 f may be released in the target organ by being pressed by the plunger.

[0138] In some embodiments, each solid bead 101 d, 101 e, 10 If contains the same one or more of the chemotherapy agent, biologic, and drug. In another embodiments, a first group of beads among the solid beads 101 d, 101 e, 10 If contains a first chemotherapy agent, biologic, or drug, and a second group of solid beads among the series of solid beads 101 d, 101 e, 10 If contains a second chemotherapy agent, biologic, or drug that is different from the first chemotherapy agent, biologic, or drug. In still another embodiments, the series of solid beads 100C further includes a third group of solid beads containing a third chemotherapy agent, biologic, or drug that is different from the first and second chemotherapy agent, biologic, and / or drug. In some embodiments, the amount of each of the first and second groups and each of the first, second and third groups is equal or similar.

[0139] In some embodiments, a first portion of the series of solid beads 100C contains a chemotherapy agent and a second portion of the series of solid beads 100C contain one or moreof a biologic and a drug. In some embodiments, the series of solid beads 100C includes solid beads containing a chemotherapy drug and solid beads containing an antineoplastic agent. In some embodiments, the chemotherapy drug includes or is gemcitabine. In some embodiments, the antineoplastic agent includes or is docetaxel.

[0140] In various embodiments, the series of implantable solid beads 100C are held together with a coating 120 on an exterior surface of the solid beads 101 d, 101 e, 101 f.

[0141] In various embodiments, the coating 120 is a soluble biocompatible coating.

[0142] In various embodiments, the dissolvable biocompatible coating 120 is urinesoluble or water-soluble.

[0143] In various embodiments, the soluble biocompatible coating 120 includes polyethylene glycol (PEG), polyvinyl alcohol (PVA), Xanatham gum, cellulose ethers, or Biodegradable polyphosphoesters (PPE).

[0144] In various embodiments, when the series of implantable solid beads 100C is delivered into the target organ, the soluble biocompatible coating 120 is dissolved prior to dissolving of the series of implantable solid beads.

[0145] In various embodiments, the soluble biocompatible coating 120 is dissolved such that each solid bead 101 d, lOle, 10 If is separated from the series of implantable solid beads 100C and is dispersed individually in the target organ, each solid bead subsequently dissolving to release a chemotherapy drug over time.

[0146] In various embodiments, the chemotherapy drug is released for at least 4 weeks subsequent to separation of each solid bead lOld, lOle, lOlf from the series of implantable solid beads 100C.

[0147] In various embodiments, the delivery system further includes a urinary catheter having a central channel and configured to deliver the series of implantable solid beads 100C within the target organ.

[0148] In various embodiments, each solid bead lOld, lOle, lOlf is elongated to have a cylindrical shape.

[0149] In various embodiments, the series of implantable solid beads 100C is severable to form at least one sub-series of implantable solid beads lOld, lOle, lOlf.

[0150] In various embodiments, each solid bead lOld, lOle, lOlf is impregnated with a radiopaque material.

[0151] In various embodiments, the radiopaque material is visible on X-ray.

[0152] In various embodiments, the dissolvable compound is a water dissolvable compound that includes a non-biological sugar.

[0153] In various embodiments, the target organ is a bladder, a ureter, or a kidney.

[0154] In various embodiments, the chemotherapy powder includes a chemotherapy drug that is effective for treating cancer.Method of Administering a Drug Through Urethral Access

[0155] Various embodiments of the present invention provide for a method of administering a drug to a patient in need thereof. The method includes inserting a wire 130 through the patient's urethra and bladder and into the patient's ureter, as shown in FIG. 3 A; placing a series of implantable beads 100A or 100B over the wire 130, as shown in FIG. 3B, and advancing the series of implantable beads 100A or 100B into the patient’s kidney by pushing a stent 310 loaded over the wire 130, each bead 101a, 101b, 101c of the series of implantable beads 100A or 100B containing one or more of a chemotherapy agent, a biologic, and a drug; deploying the stent 310 within the ureter, as shown in FIG. 3C; and allowing the beads 101a, 101b, 101c in the kidney to slowly elute the drug out of the beads into the patient’s renal collecting system, ureter, and bladder. Each bead 101a, 101b, 101c of the series of implantable beads 100A or 100B has a bead core through which a central channel 110 passes, the wire 130 passing through the central channel 110 of each bead 101a, 101b, 101c while the series of implantable beads 100A or 100B is positioned in its entirety in the kidney via the wire 130.

[0156] In various embodiments, the method further includes inserting a urinary catheter having a central channel such that the wire 130 and the series of implantable beads 100 A or 100B are passed up the ureter through the central channel of the urinary catheter and delivered within the kidney.

[0157] In various embodiments, the method further includes placing a cystoscope 200 in the bladder by inserting the cystoscope into the urethra such that the wire 130 and the series of implantable beads 100A or 100B are passed up the ureter through the cystoscope 200.

[0158] In various embodiments, each bead 101a, 101b, 101c of the series of implantable beads 100A or 100B is elongated to have a cylindrical shape.

[0159] In various embodiments, the implantable beads 101a, 101b, 101c are chained.

[0160] In various embodiments, the chained implantable beads or the series of implantable beads 100A or 100B is severable to form at least one sub-series of implantable beads.

[0161] In various embodiments, the series of implantable beads 100A or 100B is held together with a coating 120 on an exterior surface of the bead core.

[0162] In various embodiments, the coating 120 is a soluble biocompatible coating.

[0163] In various embodiments, the dissolvable biocompatible coating 120 is urinesoluble or water-soluble.

[0164] In various embodiments, the soluble biocompatible coating 120 includes polyethylene glycol (PEG), polyvinyl alcohol (PVA), Xanatham gum, cellulose ethers, or Biodegradable polyphosphoesters (PPE).

[0165] In various embodiments, when the series of implantable beads 100 A or 100B is delivered into the kidney, the soluble biocompatible coating 120 is dissolved prior to dissolving of the series of implantable beads 100 A or 100B.

[0166] In various embodiments, the soluble biocompatible coating 120 is dissolved such that each bead 101a, 101b, 101c is separated from the series of implantable beads 100A or 100B and is dispersed individually in the kidney, each bead, subsequently, dissolving to release the one or more of the chemotherapy agent, biologic, and drug over time.

[0167] In various embodiments, the one or more of the chemotherapy agent, biologic, and drug is released for at least 4 weeks subsequent to separation of each bead 101a, 101b, 101c from the series of implantable beads 100 A or 100B.

[0168] In various embodiments, each bead 101a, 101b, 101c is impregnated with a radiopaque material visible on X-ray such that the beads are trackable.

[0169] In various embodiments, the one or more of the chemotherapy agent, biologic, and drug is effective for treating cancer including urothelial cancer or bladder cancer.

[0170] In various embodiments, the stent 310 is left in the ureter to prevent the chemotherapy beads 101a, 101b, 101c from passing from the kidney as the beads 101a, 101b, 101c dissolve.

[0171] In various embodiments, the one or more of the chemotherapy agent, biologic, and drug includes a chemotherapy powder mixed with a dissolvable compound.

[0172] In various embodiments, the dissolvable compound is a water dissolvable compound that includes a non-biological sugar.Method of Administering a Drug Through Percutaneous Access

[0173] Referring to FIG. 4, various embodiments of the present invention provide for a method of administering a drug to a patient in need thereof. The method includes at step 400 inserting a wire 130 through a nephrostomy tube into the patient's kidney. Then, at step 402, the method further includes placing a series of implantable beads 100 A or 100B over the wire 130 and advancing the series of implantable beads 100 A or 100B into the patient’s kidney over the wire 130 by using a pushing tool 310, each bead 101a, 101b, 101c of the series of implantablebeads 100 A or 100B containing one or more of a chemotherapy agent, a biologic, and a drug. Then, at step 404, the method further includes removing the wire 130 from the nephrostomy tube; and allowing the beads 101a, 101b, 101c in the kidney to slowly elute the drug out of the beads into the patient’s renal collecting system, ureter, and bladder. Each bead 101a, 101b, 101c of the series of implantable beads 100 A or 100B has a bead core through which a central channel 110 passes, the wire 130 passing through the central channel of each bead while the series of implantable beads 100A or 100B is positioned in its entirety in the kidney via the wire 130.

[0174] In various embodiments, each bead 101a, 101b, 101c of the series of implantable beads 100A or 100B is elongated to have a cylindrical shape.

[0175] In various embodiments, the implantable beads 101a, 101b, 101c are chained.

[0176] In various embodiments, the chained plurality of beads 101a, 101b, 101c or the series of implantable beads 100A or 100B is severable to form at least one sub-series of implantable beads.

[0177] In various embodiments, the series of implantable beads 100B is held together with a coating 120 on an exterior surface of the bead core.

[0178] In various embodiments, the coating 120 is a soluble biocompatible coating.

[0179] In various embodiments, the dissolvable biocompatible coating 120 is urinesoluble or water-soluble.

[0180] In various embodiments, the urine or water-soluble biocompatible coating 120 includes polyethylene glycol (PEG), polyvinyl alcohol (PVA), Xanatham gum, cellulose ethers, or Biodegradable polyphosphoesters (PPE).

[0181] In various embodiments, when the series of implantable beads 100 A or 100B is delivered into the kidney, the soluble biocompatible coating 120 is dissolved prior to dissolving of the series of implantable beads 100 A or 100B.

[0182] In various embodiments, the soluble biocompatible coating 120 is dissolved such that each bead 101a, 101b, 101c is separated from the series of implantable beads 100A or 100B and is dispersed individually in the kidney, each bead, subsequently, dissolving to release the one or more of the chemotherapy agent, biologic, and drug over time.

[0183] In various embodiments, the one or more of the chemotherapy agent, biologic, and drug is released for at least 4 weeks subsequent to separation of each bead 101a, 101b, 101c from the series of implantable beads 100 A or 100B.

[0184] In various embodiments, each bead 101a, 101b, 101c is impregnated with a radiopaque material visible on X-ray such that the beads are trackable.

[0185] In various embodiments, the one or more of the chemotherapy agent, biologic, and drug is effective for treating cancer including urothelial cancer or bladder cancer.

[0186] In various embodiments, a dosage of the one or more of the chemotherapy agent, biologic, and drug is controlled by advancing a target number of beads 101a, 101b, 101c corresponding to the dosage over the wire 130 into the patient’s kidney.

[0187] In various embodiments, the method further includes placing the nephrostomy tube into the kidney.

[0188] In various embodiments, the drug includes a chemotherapy powder mixed with a dissolvable compound.

[0189] In various embodiments, the dissolvable compound is a water dissolvable compound that includes a non-biological sugar.

[0190] Referring to FIG. 5, various embodiments of the present invention provide for a method of administering a drug to a patient in need thereof. The method includes at step 500 loading a series of solid beads 101 d, 101 e, 10 If into a tube. In some embodiments, the series of solid beads lOld, lOle, 10 If are coated such that the sold beads stick together. In some embodiments, the series of solid beads 101 d, lOle, 10 If are loaded into the tube with a plunger, the plunger pressing the back of the series of solid beads 101 d, lOle, 10 If. Then, at step 502, the method further includes inserting the tube into a patient. Then, at step 504, the method further includes advancing the series of implantable beads 100C through the tube into the patient’s organ, such as the bladder or kidney, by pressing the series of implantable beads 100C with the plunger. The beads 101 d, lOle, 10 If in the patient’s organ are allowed to slowly elute the drug out of the beads into the patient’s renal collecting system, ureter, and bladder. Then, at step 506, the method further includes retracting the tube and plunger from the patient’s organ.

[0191] In various embodiments, each bead 101 d, lOle, 10 If of the series of implantable beads 100C is elongated to have a cylindrical shape.

[0192] In various embodiments, the implantable beads 101 d, lOle, 10 If are chained.

[0193] In various embodiments, the chained plurality of beads lOld, lOle, lOlf or the series of implantable beads 100C is severable to form at least one sub-series of implantable beads.

[0194] In various embodiments, the series of implantable beads 100C is held together with a coating 120 on an exterior surface of the solid beads 101 d, 101 e, 101 f.

[0195] In various embodiments, the coating 120 is a soluble biocompatible coating.

[0196] In various embodiments, the dissolvable biocompatible coating 120 is urinesoluble or water-soluble.

[0197] In various embodiments, the urine or water-soluble biocompatible coating 120 includes polyethylene glycol (PEG), polyvinyl alcohol (PVA), Xanatham gum, cellulose ethers, or Biodegradable polyphosphoesters (PPE).

[0198] In various embodiments, when the series of implantable beads 100C is delivered into the patient’s organ, the soluble biocompatible coating 120 is dissolved prior to dissolving of the series of implantable beads 100C.

[0199] In various embodiments, the soluble biocompatible coating 120 is dissolved such that each bead lOld, lOle, lOlf is separated from the series of implantable beads 100C and is dispersed individually in the patient’s organ, each bead lOld, lOle, lOlf, subsequently, dissolving to release the one or more of the chemotherapy agent, biologic, and drug over time.

[0200] In various embodiments, the one or more of the chemotherapy agent, biologic, and drug is released for at least 4 weeks subsequent to separation of each bead 101 d, lOle, 10 If from the series of implantable beads 100C.

[0201] In various embodiments, each bead lOld, lOle, lOlf is impregnated with a radiopaque material visible on X-ray such that the beads are trackable.

[0202] In various embodiments, the one or more of the chemotherapy agent, biologic, and drug is effective for treating cancer including urothelial cancer or bladder cancer.

[0203] In various embodiments, a dosage of the one or more of the chemotherapy agent, biologic, and drug is controlled by advancing a target number of beads lOld, lOle, lOlf corresponding to the dosage through the tube into the patient’s organ.

[0204] In various embodiments, the method further includes placing a nephrostomy tube or a urinary catheter into the patient’s organ.

[0205] In various embodiments, the drug includes a chemotherapy powder mixed with a dissolvable compound.

[0206] In various embodiments, the dissolvable compound is a water dissolvable compound that includes a non-biological sugar.Series of Implantable Chemotherapy Beads

[0207] Various embodiments of the present invention provide for a series of implantable beads 100 A or 100B, as shown in FIGS. 1 A and IB.

[0208] In various embodiments, each bead 101a, 101b, 101c of the series of implantable beads 100 A or 100B has a bead core through which a central channel 110 passes, the bead core containing a chemotherapy powder mixed with a dissolvable compound.

[0209] In various embodiments, each bead 101a, 101b, 101c is elongated to have a cylindrical shape.

[0210] In various embodiments, the series of implantable beads 100A or 100B is severable.

[0211] In various embodiments, the series of implantable beads 100A or 100B is held together with a urine or water-soluble biocompatible coating 120.

[0212] In various embodiments, each bead 101a, 101b, 101c is impregnated with a radiopaque material visible on X-ray.

[0213] In various embodiments, each bead 101a, 101b, 101c includes a drug for treating cancer comprising urothelial cancer or bladder cancer. In various embodiments, the series of implantable beads 100A or 100B is movable via a wire 130 passing through the central channel 110 of each bead 101a, 101b, 101c and is implantable in a patient’s kidney for prolonged release of the drug into the patient’s renal collecting system, ureter, and bladder.

[0214] In various embodiments, the soluble biocompatible coating 120 is dissolved prior to dissolving of the series of implantable beads 100A or 100B, and the drug is released for at least 4 weeks subsequent to separation of each bead 101a, 101b, 101c from the series of implantable beads.

[0215] Various embodiments of the present invention provide for a series of implantable solid beads 100C, as shown in FIG. 1C.

[0216] In various embodiments, each solid bead lOld, lOle, lOlf is elongated to have a cylindrical shape.

[0217] In various embodiments, the series of implantable solid beads 100C is severable.

[0218] In various embodiments, the series of implantable solid beads 100C is held together with a urine or water-soluble biocompatible coating 120.

[0219] In various embodiments, each solid bead lOld, lOle, lOlf is impregnated with a radiopaque material visible on X-ray.

[0220] In various embodiments, each solid bead 101 d, 101 e, 10 If includes a drug for treating cancer comprising urothelial cancer orbladder cancer. In various embodiments, the series of implantable solid beads 100C is implantable in a target organ of a patient, such as the bladder or kidney, for prolonged release of the drug into the patient’s renal collecting system, ureter, and bladder. In various embodiments, the solid beads 101 d, lOle, 10 If are loaded into a tube, and then the tube is inserted into the target organ, the solid beads 101 d, lOle, 10 If being pressed with the plunger to deposit the solid beads 101 d, lOle, 101 f into the target organ. Compared to the beads 101a, 101b, 101c having a central channel, the solid beads lOld, lOle, lOlf that do not have acentral channel may have a larger payload and an increased content of therapeutic material within the beadslOld, lOle, lOlf.

[0221] In various embodiments, the soluble biocompatible coating 120 is dissolved prior to dissolving of the series of implantable solid beads 100C, and the drug is released for at least 4 weeks subsequent to separation of each solid bead lOld, lOle, 101 f from the series of implantable solid beads 100C.

[0222] Various embodiments of the invention are described above in the Detailed Description. While these descriptions directly describe the above embodiments, it is understood that those skilled in the art may conceive modifications and / or variations to the specific embodiments shown and described herein. Any such modifications or variations that fall within the purview of this description are intended to be included therein as well. Unless specifically noted, it is the intention of the inventors that the words and phrases in the specification and claims be given the ordinary and accustomed meanings to those of ordinary skill in the applicable art(s).

[0223] The foregoing description of various embodiments of the invention known to the applicant at this time of filing the application has been presented and is intended for the purposes of illustration and description. The present description is not intended to be exhaustive nor limit the invention to the precise form disclosed and many modifications and variations are possible in the light of the above teachings. The embodiments described serve to explain the principles of the invention and its practical application and to enable others skilled in the art to utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated. Therefore, it is intended that the invention not be limited to the particular embodiments disclosed for carrying out the invention.

[0224] While particular embodiments of the present invention have been shown and described, it will be obvious to those skilled in the art that, based upon the teachings herein, changes and modifications may be made without departing from this invention and its broader aspects and, therefore, the appended claims are to encompass within their scope all such changes and modifications as are within the true spirit and scope of this invention. As used herein the term “comprising” or “comprises” is used in reference to compositions, methods, and respective component(s) thereof, that are useful to an embodiment, yet open to the inclusion of unspecified elements, whether useful or not. It will be understood by those within the art that, in general, terms used herein are generally intended as “open” terms (e.g., the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” etc.). Although the open-ended term “comprising,” as a synonym of terms such as including, containing,or having, is used herein to describe and claim the invention, the present invention, or embodiments thereof, may alternatively be described using alternative terms such as “consisting of’ or “consisting essentially of.”

[0225] Unless stated otherwise, the terms “a” and “an” and “the” and similar references used in the context of describing a particular embodiment of the application (especially in the context of claims) may be construed to cover both the singular and the plural. The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein may be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (for example, “such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the application and does not pose a limitation on the scope of the application otherwise claimed. The abbreviation, “e.g.” is derived from the Latin exempli gratia, and is used herein to indicate a nonlimiting example. Thus, the abbreviation “e.g.” is synonymous with the term “for example.” No language in the specification should be construed as indicating any non-claimed element essential to the practice of the application.

[0226] Groupings of alternative elements or embodiments of the present disclosure disclosed herein are not to be construed as limitations. Each group member may be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group may be included in, or deleted from, a group for reasons of convenience and / or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A delivery system comprising: a series of implantable beads, each bead of the series of implantable beads having a bead core through which a central channel passes, the bead core containing one or more of a chemotherapy agent, a biologic, and a drug mixed with a dissolvable compound; and a wire configured for guiding each bead, individually or as a group held together by a water-soluble coating, into a target organ, the wire passing through the central channel of each bead while the series of implantable beads is positioned in its entirety in the target organ via the wire.

2. The delivery system of claim 1, wherein the series of implantable beads is held together with a coating on an exterior surface of the bead core.

3. The delivery system of claim 2, wherein the coating is a soluble biocompatible coating.

4. The delivery system of claim 3, wherein the dissolvable biocompatible coating is urine-soluble or water-soluble.

5. The delivery system of claim 3, wherein the soluble biocompatible coating includes polyethylene glycol (PEG), polyvinyl alcohol (PVA), Xanatham gum, cellulose ethers, or Biodegradable polyphosphoesters (PPE).

6. The delivery system of claim 3, wherein, when the series of implantable beads is delivered into the target organ, the soluble biocompatible coating is dissolved prior to dissolving of the series of implantable beads.

7. The delivery system of claim 6, wherein the target organ is a kidney, and the soluble biocompatible coating and the series of implantable beads are dissolved in the kidney.

8. The delivery system of claim 3, wherein, when the series of implantable beads is delivered into the target organ, the soluble biocompatible coating is dissolved after dissolving of the series of implantable beads.

9. The delivery system of claim 8, wherein the target organ is a bladder, and the soluble biocompatible coating and the series of implantable beads are dissolved in the bladder.

10. The delivery system of claim 9, wherein the soluble biocompatible coating is dissolved such that each bead is separated from the series of implantable beads and is dispersed individually in the target organ, each bead, subsequently, dissolving to release the one or more of the chemotherapy agent, biologic, and drug over time.

11. The delivery system of claim 10, wherein the one or more of the chemotherapy agent, biologic, and drug is released for at least 4 weeks subsequent to separation of each bead from the series of implantable beads.

12. The delivery system of claim 1, further comprising a urinary catheter having a central channel and configured to deliver the wire and the series of implantable beads within the target organ.

13. The delivery system of claim 1, wherein each bead is elongated to have a cylindrical shape.

14. The delivery system of claim 1, wherein the series of implantable beads are severable to form at least one sub-series of implantable chemotherapy beads.

15. The delivery system of claim 1, wherein each bead is impregnated with a radiopaque material.

16. The delivery system of claim 15, wherein the radiopaque material is visible on X- ray.

17. The delivery system of claim 1, wherein the dissolvable compound is a water dissolvable compound that includes a non-biological sugar.

18. The delivery system of claim 1, wherein the target organ is a bladder, a ureter, or a kidney.

19. The delivery system of claim 1, wherein the bead core contains the same chemotherapy agent, biologic, or drug.

20. The delivery system of claim 1, wherein all of the series of implantable beads contain the same chemotherapy agent, biologic, or drug.

21. The delivery system of claim 1, wherein the series of implantable beads contain at least two different types of beads, each type of beads containing a different chemotherapy agent, biologic, or drug.

22. The delivery system of claim 21, wherein the series of implantable beads includes a first group of implantable beads containing a chemotherapy agent and a second group of implantable beads containing one or more of a biologic and a drug.

23. The delivery system of claim 22, wherein each of the first group and the second group is a half or about a half of the series of implantable beads.

24. The delivery system of claim 21, wherein the series of implantable beads includes a first group of implantable beads containing a chemotherapy drug and a second group of implantable beads containing an antineoplastic agent.

25. The delivery system of claim 24, wherein the chemotherapy drug comprises gemcitabine.

26. The delivery system of claim 25, wherein the antineoplastic agent comprises docetaxel.

27. The delivery system of claim 1, wherein the one or more of the chemotherapy agent, biologic, and drug is effective for treating cancer.

28. The delivery system of claim 27, wherein the cancer includes urothelial cancer or bladder cancer.

29. A method of administering a drug to a patient in need thereof, the method comprising: inserting a wire through the patient's urethra and bladder and into the patient's ureter; placing a series of implantable beads over the wire and advancing the series of implantable beads into the patient’s kidney by pushing a stent loaded over the wire, each bead of the series of implantable beads containing one or more of a chemotherapy agent, a biologic, and a drug; deploying the stent within the patient’s ureter; and allowing each bead in the patient’s kidney to slowly elute the one or more of the chemotherapy agent, biologic, and drug out of each bead into the patient’s renal collecting system, ureter, and bladder, wherein each bead has a bead core through which a central channel passes, the wire passing through the central channel of each bead while the series of implantable beads is positioned in its entirety in the kidney via the wire.

30. The method of claim 29, further comprising: inserting a urinary catheter having a central channel such that the wire and the series of implantable beads are passed up the ureter through the central channel of the urinary catheter and delivered within the patient’s kidney.

31. The method of claim 29, further comprising: placing a cystoscope in the patient’s bladder by inserting the cystoscope into the patient’s urethra such that the wire and the series of implantable beads are passed up the patient’s ureter through the cystoscope.

32. The method of any one of claims 29-31, wherein: each bead of the series of implantable beads is elongated to have a cylindrical shape; the implantable beads are chained; and / or the chained implantable beads or the series of implantable beads is severable to form at least one sub-series of implantable beads.

33. The method of any one of claims 29-32, wherein the series of implantable beads are held together with a coating on an exterior surface of the bead core.

34. The method of claim 33, wherein the coating is a soluble biocompatible coating.

35. The method of claim 34, wherein the dissolvable biocompatible coating is urinesoluble or water-soluble.

36. The method of claim 34 or claim 35, wherein the soluble biocompatible coating includes polyethylene glycol (PEG), polyvinyl alcohol (PVA), Xanatham gum, cellulose ethers, or Biodegradable polyphosphoesters (PPE).

37. The method of any one of claims 33-36, wherein, when the series of implantable beads is delivered into the patient’s kidney, the soluble biocompatible coating is dissolved prior to dissolving of the series of implantable beads.

38. The method of any one of claims 33-37, wherein the soluble biocompatible coating is dissolved such that each bead is separated from the series of implantable beads and is dispersed individually in the patient’s kidney, each bead, subsequently, dissolving to release the one or more of the chemotherapy agent, biologic, and drug over time.

39. The method of any one of claims 33-38, wherein the one or more of the chemotherapy agent, biologic, and drug is released for at least 4 weeks subsequent to separation of each bead from the series of implantable beads.

40. The method of any one of claims 29-39, wherein each bead is impregnated with a radiopaque material visible on X-ray such that the beads are trackable.

41. The method of any one of claims 29-40, wherein the one or more of the chemotherapy agent, biologic, and drug is effective for treating cancer including urothelial cancer or bladder cancer.

42. The method of any one of claims 29-41, wherein the stent is left in the patient’s ureter to prevent the beads from passing from the patient’s kidney as the beads dissolve.

43. The method of any one of claims 29-42, wherein the one or more of chemotherapy agent, biologic, and drug includes a chemotherapy powder mixed with a dissolvable compound.

44. The method of claim 43, wherein the dissolvable compound is a water dissolvable compound that includes a non-biological sugar.

45. The method of claims 29-44, wherein the series of implantable beads contain a same chemotherapy agent, biologic, or drug.

46. The method of claims 29-44, wherein the series of implantable beads include a first group of implantable beads and a second group of implantable beads, implantable beads ofthe first group and implantable beads of the second group containing a different chemotherapy agent, biologic, or drug.

47. The method of claim 46, wherein the first group contains a chemotherapy agent and the second group contains one or more of a biologic and a drug.

48. The method of claim 46, wherein the first group contains a chemotherapy drug and the second group contains an antineoplastic agent.

49. The delivery system of claim 48, wherein the chemotherapy drug comprises gemcitabine.

50. The delivery system of claim 49, wherein the antineoplastic agent comprises docetaxel.

51. A method of administering one or more of a chemotherapy agent, a biologic, and a drug to a patient in need thereof, the method comprising: inserting a wire through a nephrostomy tube into the patient's kidney; placing a series of implantable beads over the wire and advancing the series of implantable beads into the patient’s kidney over the wire by using a pushing tool, each bead of the series of implantable beads containing the one or more of the chemotherapy agent, biologic, and drug; removing the wire from the nephrostomy tube; and allowing the beads in the patient’s kidney to slowly elute the one or more of the chemotherapy agent, biologic, and drug out of the beads into the patient’s renal collecting system, ureter, and bladder, wherein each bead of the series of implantable beads has a bead core through which a central channel passes, the wire passing through the central channel of each bead while the series of implantable beads is positioned in its entirety in the patient’s kidney via the wire.

52. The method of claim 51, wherein: each bead of the series of implantable beads is elongated to have a cylindrical shape; the implantable beads are chained; and / or the chained plurality of beads or the series of implantable beads is severable to form at least one sub-series of implantable beads.

53. The method of any one of claims 51-52, wherein the series of implantable beads is held together with a coating on an exterior surface of the bead core.

54. The method of claim 53, wherein the coating is a soluble biocompatible coating.

55. The method of claim 54, wherein the dissolvable biocompatible coating is urinesoluble or water-soluble.

56. The method of claim 54 or claim 55, wherein the urine or water-soluble biocompatible coating comprises polyethylene glycol (PEG), polyvinyl alcohol (PVA),Xanatham gum, cellulose ethers, or Biodegradable polyphosphoesters (PPE).

57. The method of any one of claims 54-56, wherein, when the series of implantable beads is delivered into the patient’s kidney, the soluble biocompatible coating is dissolved prior to dissolving of the series of implantable beads.

58. The method of any one of claims 54-57, wherein the soluble biocompatible coating is dissolved such that each bead is separated from the series of implantable beads and is dispersed individually in the patient’s kidney, each bead, subsequently, dissolving to release the one or more of the chemotherapy agent, biologic, and drug over time.

59. The method of any one of claims 51-58, wherein the one or more of the chemotherapy agent, biologic, and drug is released for at least 4 weeks subsequent to separation of each bead from the series of implantable beads.

60. The method of any one of claims 51-59, wherein each bead is impregnated with a radiopaque material visible on X-ray such that the beads are trackable.

61. The method of any one of claims 51-60, wherein the one or more of the chemotherapy agent, biologic, and drug is effective for treating cancer including urothelial cancer or bladder cancer.

62. The method of any one of claims 51-61, wherein a dosage of the one or more of the chemotherapy agent, biologic, and drug is controlled by advancing a target number of beads corresponding to the dosage over the wire into the patient’s kidney.

63. The method of any one of claims 51-62, further comprising placing the nephrostomy tube into the kidney.

64. The method of any one of claims 51-63, wherein the one or more of the chemotherapy agent, biologic, and drug includes a chemotherapy powder mixed with a dissolvable compound.

65. The method of claim 64, wherein the dissolvable compound is a water dissolvable compound that includes a non-biological sugar.

66. A series of implantable chemotherapy beads, wherein: each chemotherapy bead of the series of implantable chemotherapy beads has a bead core through which a central channel passes, the bead core containing a chemotherapy powder mixed with a dissolvable compound; each chemotherapy bead is elongated to have a cylindrical shape; the series of implantable chemotherapy beads is severable;the series of implantable chemotherapy beads is held together with a urine or water-soluble biocompatible coating; and / or each chemotherapy bead is impregnated with a radiopaque material visible on X-ray.

67. The series of implantable chemotherapy beads of claim 66, wherein each chemotherapy bead includes one or more of a chemotherapy agent, biologic, and drug for treating cancer comprising urothelial cancer or bladder cancer.

68. The series of implantable chemotherapy beads of claim 66 or claim 67, wherein the series of implantable chemotherapy beads is movable via a wire passing through the central channel of each chemotherapy bead and is implantable in a patient’s kidney for prolonged release of the one or more of the chemotherapy agent, biologic, and drug into the patient’s renal collecting system, ureter, and bladder.

69. The series of implantable chemotherapy beads of any one of claims 66-68, wherein the soluble biocompatible coating is dissolved prior to dissolving of the series of implantable chemotherapy beads, and the one or more of the chemotherapy agent, biologic, and drug is released for at least 4 weeks subsequent to separation of each chemotherapy bead from the series of implantable chemotherapy beads.

70. A delivery system comprising: a series of implantable beads, each bead of the series of implantable beads containing one or more of a chemotherapy agent, a biologic, and a drug mixed with a dissolvable compound; a tube configured for guiding each bead, individually or as a group held together by a water-soluble coating, into a target organ; and a plunger configured for pressing the series of implantable beads into the tube and pressing the beads through the tube such that the pressed beads are released into the target organ while the series of implantable beads is positioned in in the target organ via the tube.

71. A method of administering one or more of a chemotherapy agent, a biologic, and a drug to a patient in need thereof, the method comprising: inserting a series of implantable beads that are held together by coating into a tube, each bead of the series of implantable beads containing the one or more of the chemotherapy agent, biologic, and drug; inserting the tube containing the series of implantable beads into the patient's organ; advancing the series of implantable beads through the tube into the patient’s organ by pressing the series of implantable beads with a pushing tool or a plunger; and removing the tube from the patient’s organ, wherein the beads in the patient’s organ are allowed to slowly elute the one or more of thechemotherapy agent, biologic, and drug out of the beads into the patient’s organ.

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