System for targeted delivery of therapeutic agents

• US 8,802,153 B2
• Filed: 07/25/2013
• Issued: 08/12/2014
• Est. Priority Date: 03/31/2006
• Status: Active Grant

• Current Assignee: Brigham and Women's Hospital Incorporated, Massachusetts Institute of Technology
• Original Assignee: Brigham and Women's Hospital Incorporated, Massachusetts Institute of Technology
• Inventors: Cheng, Jianjun, Farokhzad, Omid C., Langer, Robert S., Teply, Benjamin A., Zale, Stephen E.
• Primary Examiner(s): Popa, Ileana
• Application Number:
  US13/950,804
• Publication Number:
  US 20140017327A1
• Time in Patent Office: 383 Days
• Field of Search: None
• US Class Current: 424/489
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 47/549 Sugars, nucleosides, nucleotides or nucleic acids
• CPC Class Codes: A61K 47/555 pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells
• CPC Class Codes: A61K 47/593 Polyesters, e.g. PLGA or polylactide-co-glycolide
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/6935 the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol
• CPC Class Codes: A61K 47/6937 the polymer being PLGA, PLA or polyglycolic acid
• CPC Class Codes: A61K 51/0417 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 51/0491 Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
• CPC Class Codes: A61K 51/0495 Pretargeting
• CPC Class Codes: A61K 51/065 conjugates with carriers being macromolecules
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5153 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5192 Processes
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention provides a drug delivery system for targeted delivery of therapeutic agent-containing particles to tissues, cells, and intracellular compartments. The invention provides targeted particles comprising a particle, one or more targeting moieties, and one or more therapeutic agents to be delivered and pharmaceutical compositions comprising inventive targeted particles. The present invention provides methods of designing, manufacturing, and using inventive targeted particles and pharmaceutical compositions thereof.

Claims

1. A targeted particle comprising a polymer conjugated to a surfactant, hydrophilic polymer or lipid,

Wherein the particle is a nanoparticle having bound thereto a plurality of small molecule targeting moieties that specifically bind to the Zn²⁺ NAAG/PSMA binding pocket within prostate specific membrane antigen (PSMA) selected from the group consisting of 2-PMPA, GP15232, VA-033 2 MPPA, 2-MPPA, thiol and indole thiol based PSMA inhibitors, 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acid derivative PSMA inhibitors, hydroxamate derivative PSMA inhibitors, PDBA-based PSMA inhibitors, and urea-based PSMA inhibitors, and

having encapsulated or dispersed therein a taxane.

2. The targeted particle of claim 1, wherein the taxane is docetaxel or paclitaxel.

3. The targeted particle of claim 2, wherein the taxane is docetaxel.

4. The targeted particle of claim 1, wherein the conjugated polymer comprises a copolymer of two or more polymers.

5. The targeted particle of claim 1, wherein the particle comprises a second polymer not conjugated to the surfactant, hydrophilic polymer, or lipid.

6. The targeted particle of claim 4, wherein the copolymer comprises a polymer selected from the group consisting of poly(lactide-co-glycolide) (PLGA), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), polycaprolactone, and polyanhydrides.

7. The targeted particle of claim 4, wherein the copolymer comprises a polymer selected from the group consisting of polyethylenes, polycarbonates, polyanhydrides, polyhydroxyacids, polypropylfumerates, polycaprolactones, polyamides, polyacetals, polyethers, polyesters, poly(orthoesters), polycyanoacrylates, polyvinyl alcohols, polyurethanes, polyphosphazenes, polyacrylates, polymethacrylates, polycyanoacrylates, polyureas, polystyrenes, polyamines, and combinations thereof.

8. The targeted particle of claim 4, wherein the copolymer comprises polyalkylene glycol.

9. The targeted particle of claim 8, wherein the polyalkylene glycol is polyethylene glycol (PEG).

10. The targeted particle of claim 4, wherein the copolymer is a copolymer of PLA and PEG.

11. The targeted particle of claim 1 further comprising a therapeutic, prophylactic, or diagnostic agent.

12. The targeted particle of claim 1, wherein the small molecule targeting moiety is a urea-based PSMA inhibitor.

13. A method of treating cancer in a subject, comprising administering an effective amount of a targeted particle comprising a polymer conjugated to a surfactant, hydrophilic polymer or lipid,

the particle having bound thereto a plurality of small molecule targeting moieties that specifically bind to the Zn²⁺ NAAG/PSMA binding pocket within prostate specific membrane antigen (PSMA) selected from the group consisting of 2-PMPA, GPI5232, VA-033 2MPPA, 2-MPPA, thiol and indole thiol based PSMA inhibitors, 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acid derivative PSMA inhibitors, hydroxamate derivative PSMA inhibitors, PDBA-based PSMA inhibitors, and urea-based PSMA inhibitors, and

having encapsulated or dispersed therein a taxane.

14. The method of claim 13, wherein the taxane is docetaxel or paclitaxel.

15. The method of claim 14, wherein the taxane is docetaxel.

16. The method of claim 13, wherein the small molecule targeting moiety is a urea-based PSMA inhibitor.