METHODS OF SYNTHESIS AND USE OF CHEMOSPHERES

• US 20110104052A1
• Filed: 12/03/2008
• Published: 05/05/2011
• Est. Priority Date: 12/03/2007
• Status: Abandoned Application

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Geschwind, Jeffrey, Barnett, Bradley Powers
• Application Number:
  US12/746,030
• Publication Number:
  US 20110104052A1
• Time in Patent Office: Days
• US Class Current: 424/1.21
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 49/1824 coated or functionalised nanoparticles liposomes A61K49/1812; nanoemulsions A61K49/1806; micelles A61K49/1809
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents

Abstract

The present invention provides, in general, compositions comprising a hydrogel and an agent, for example a therapeutic agent or an imaging agent, for locoregional delivery. In certain preferred embodiments of the invention, the hydrogel compositions are detectable by Magnetic Responance and CT Scan and are used for locoregional delivery of therapeutic agents, for example chemotherapeutic agents. The invention also features polymer matrix compositions comprising nanoparticles that can be loaded after polymerization with bioactive agents, for example a diagnostic agent or therapeutic agent.

Claims

1. A polymer matrix comprising nanoparticles, wherein the nanoparticles are loaded after polymerization with one or more bioactive agents.

2. The polymer matrix of claim 1, wherein the one or more bioactive agents is selected from the group consisting of:

a diagnostic agent, an imaging agent, a contrast agent, a radioactive isotope, and a therapeutic agent.

3. The polymer matrix of claim 1, in which the nanoparticles irreversibly interact with the bioactive agent.

4. The polymer matrix of claim 1, in which the nanoparticles reversibly interact with the bioactive agent.

5. The polymer matrix of claim 1 in which nanoparticles are undecorated metallic nanoparticles.

6. The polymer matrix of claim 1 in which nanoparticles are decorated metallic nanoparticles.

7. The polymer matrix of claim 6 wherein the decorated metallic nanoparticles are decorated with one or more elements selected from the group consisting of:

dextran, PEG, streptavidin, biotin, antibodies, antibody fragments, ligands and aptamers.

8. The polymer matrix of claim 1, wherein the nanoparticles are coated with streptavidin.

9. The polymer matrix of claim 1, wherein the bioactive agent is conjugated to biotin.

10-12. -12. (canceled)

13. A method of producing a therapeutic polymer matrix comprising nanoparticles loaded with one or more bioactive agents comprising:

polymerizing a matrix comprising polymers and nanoparticles; and

incubating the nanoparticles and the polymer matrix after polymerization with one or more bioactive agents for a time sufficient to load the nanoparticle and polymer matrix with the agent,

thereby producing a polymer matrix comprising nanoparticles loaded with one or more bioactive agents.

14-15. -15. (canceled)

16. A method of producing a therapeutic polymer matrix in a subject tissue comprising:

administering a nanoparticle and polymer matrix to a subject; and

loading the nanoparticles with a bioactive agent,

thereby producing a therapeutic polymer matrix in a subject tissue.

17-19. -19. (canceled)

20. A method of embolizing polymer microspheres containing streptavidin coated nanoparticles in a patient tumor comprising systemically infusing yttrium 90-y biotin into the patient so that yttrium 90-y biotin accumulates at the site of embolization and interacts with the streptavidin coated nanoparticles.

21-22. -22. (canceled)

23. A method of producing a polymer matrix comprising nanoparticles wherein the nanoparticles are liposomes with an aqueous core comprising:

producing a liposome suspension; and

forcing the liposome suspension through a calibrated porous membrane before introduction of the liposome into the polymer,

thereby producing a polymer matrix comprising nanoparticles wherein the nanoparticles are liposomes with an aqueous core.

24-27. -27. (canceled)

28. A method of treating a subject comprising administering an alginate liposome polymer matrix to a treatment area of the subject, wherein the polymer matrix comprises a potentially radioactive isotope;

exposing the treatment area of the subject to neutrons, protons, electrons, or high energy photons to activate the potentially radioactive isotope; and

providing AMF thermotherapy,

thereby treating the subject.

29. The method of claim 28, wherein the alginate liposome polymer matrix further comprises one or more of a radioisotope, potential radioactive isotope or a chemotherapeutic agent.

30-33. -33. (canceled)

34. A kit comprising the polymer matrix comprising nanoparticles wherein the nanoparticles are loaded after polymerization with one or more bioactive agents, and instructions for use, or

a kit comprising the polymer matrix comprising nanoparticles wherein the nanoparticles are loaded after polymerization with one or more bioactive agents, and instructions for use in embolization, or

a kit comprising the polymer matrix comprising nanoparticles wherein the nanoparticles are loaded after polymerization with one or more bioactive agents, and instructions for therapeutic use, or

a composition comprising a hydrogel and a bioactive agent that forms one or more microspheres.

35-46. -46. (canceled)

47. A method of forming one or more microspheres comprising bioactive agent, the method comprising:

adding bioactive agent to a hydrogel solution;

adding the agent and hydrogel solution to a mineral oil bath; and

initiating polymerization;

thereby forming one or more microspheres comprising bioactive agent.

48-52. -52. (canceled)

53. A method for treating a subject having a vascular or non-vascular condition, the method comprising the step of administering to the subject a composition comprising a hydrogel and a bioactive agent that forms one or more microspheres, or

a method for treating a subject having a vascular or non-vascular hemorrhage, the method comprising the step of administering to the subject a composition comprising a hydrogel and a bioactive agent that forms one or more microspheres, or

a method for treating a subject having a neoplastic growth, the method comprising the step of administering to the subject a composition comprising a hydrogel and a bioactive agent that forms one or more microspheres, thereby treating the subject, or

a method for the selective delivery of a therapeutic agent to a targeted non-occluded vessel by administering to the subject a hydrogel and a bioactive agent that forms one or more microspheres based biomaterial, or

a method for the controlled release of an agent in a subject, the method comprising the steps of:

administering to the subject a hydrogel and a bioactive agent that forms one or more microspheres, or

a method for the controlled release of a label in a subject, the method comprising the steps of administering to the subject a hydrogel and a bioactive agent that forms one or more microspheres, or

a method for the controlled release of a contrast agent in a subject, the method comprising the steps of administering to the subject a hydrogel and a bioactive agent that forms one or more microspheres, or

a method comprising administering a cell or therapeutic compound in a hydrogel that forms one or more microspheres to a target area in a patient, or

a method for the selective control of bulking or remodeling in a subject, the method comprising the steps of;

(i) administering to the subject a hydrogel based biomaterial to a targeted area; and

(ii) polymerizing the hydrogel, thereby controlling bulking or remodeling in a subject.

54-105. -105. (canceled)