Use of buckysome or carbon nanotube for drug delivery

• US 7,070,810 B2
• Filed: 02/14/2003
• Issued: 07/04/2006
• Est. Priority Date: 02/14/2002
• Status: Expired due to Fees

• Current Assignee: Luna Innovations, Inc.
• Original Assignee: C Sixty Incorporated
• Inventors: Hirsch, Andreas, Sagman, Uri, Wilson, Stephen R.
• Primary Examiner(s): HARTLEY, MICHAEL G
• Application Number:
  US10/367,646
• Publication Number:
  US 20030180491A1
• Time in Patent Office: 1,236 Days
• Field of Search: 424/489, 424/450, 560/80, 560/76, 560/8, 514/709, 423/445.B, 516/901, 977/DIG.1
• US Class Current: 424/489
• CPC Class Codes: A61K 47/6949 inclusion complexes, e.g. clathrates, cavitates or fullerenes
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: Y10S 516/901 Substantially pure carbon, e.g. graphite, lamp black, carbon black, fullerenes
• CPC Class Codes: Y10S 977/734 Fullerenes, i.e. graphene-based structures, such as nanohorns, nanococoons, nanoscrolls or fullerene-like structures, e.g. WS2 or MoS2 chalcogenide nanotubes, planar C3N4, etc.
• CPC Class Codes: Y10T 428/1352 Polymer or resin containing [i.e., natural or synthetic]
• CPC Class Codes: Y10T 428/1393 Multilayer [continuous layer]

Abstract

Compositions and methods for administering a therapeutic agent to a mammal are disclosed. The compositions comprise either (i) vesicles comprising an amphiphilic substituted fullerene, wherein the therapeutic agent is present in the vesicle interior or between layers of the vesicle wall, (ii) a substituted fullerene, comprising a fullerene core and a functional moiety, wherein the therapeutic agent is associated with the substituted fullerene, or (iii) carbon nanotubes, wherein the therapeutic agent is covalently bonded to the carbon nanotubes.

Claims

1. A vesicle having an interior, an exterior, and a wall, wherein the wall comprises one or more layers, wherein each layer comprises a substituted fullerene having structure I:

(B)_b—

C_n-(A)_a 

 

(I)

wherein C_n is a fullerene moiety comprising n carbon atoms, wherein n is an integer and 60≦

n≦

240;

B is an organic moiety comprising from 1 to about 40 polar headgroup moieties;

b is an integer and 1≦

b≦

5;

each B is covalently bonded to the C_n through 1 or 2 carbon-carbon, carbon-oxygen, or carbon-nitrogen bonds;

A is an organic moiety comprising a terminus proximal to the C_n and one or more termini distal to the C_n, wherein the termini distal to the C_n each comprise —

C_xH_y, wherein x is an integer and 8≦

x≦

24, and y is an integer and 1≦

y≦

2x+1;

a is an integer, 1≦

a≦

5;

2≦

b+a≦

6; and

each A is covalently bonded to the C_n through 1 or 2 carbon-carbon, carbon-oxygen, or carbon-nitrogen bonds,

wherein the vesicle wall comprises at least about 50 mol % the substituted fullerene; and

,

wherein the interior of the vesicle, a portion of the wall between two layers, or both comprise a therapeutic agent.

2. The vesicle of claim 1, wherein the wall is a bilayer membrane.

3. The vesicle of claim 1, wherein the wall is a monolayer membrane.

4. The vesicle of claim 1, wherein B comprises 18 polar headgroup moieties;

A comprises two termini distal to the C_n;

x=12;

y=25;

b=1; and

a=5.

5. The vesicle of claim 4, wherein the substituted fullerene molecule has structure II:

6. The vesicle of claim 5, wherein the substituted fullerene molecule has the structure

7. The vesicle of claim 1, wherein from about 0.01 mole % to about 100 mole % of the substituted fullerene molecules further comprise a functional group covalently linked to a B group.

8. The vesicle of claim 7, wherein the functional group is selected from the group consisting of biotin-containing moieties, antigen-binding moieties, and tissue-recognition moieties.

9. The vesicle of claim 8, wherein the substituted fullerene comprising the functional group has the structure.

10. The vesicle of claim 1, wherein the wall comprises at least about 75 mol % a substituted fullerene having structure I.

11. The vesicle of claim 1, wherein the therapeutic agent is an anti-cancer drug.

12. A method of administering a therapeutic agent to a mammal, comprising:

(i) administering a solution comprising a pharmaceutically effective amount of the therapeutic agent, wherein the therapeutic agent is present in (a) the interior of a vesicle having an interior, an exterior, and a wall, (b) a portion of the wall between two layers, or (c) both, to the mammal, wherein the wall comprises one or more layers, wherein each layer comprises a substituted fullerene having structure I;

(B)_b—

C_n-(A)_a 

 

(I)

wherein C_n is a fullerene moiety comprising n carbon atoms, wherein n is an integer and 60≦

n≦

240;

B is an organic moiety comprising from 1 to about 40 polar headgroup moieties;

b is an integer and 1≦

b≦

5;

each B is covalently bonded to the C_n through 1 or 2 carbon-carbon, carbon-oxygen, or carbon-nitrogen bonds;

A is an organic moiety comprising a terminus proximal to the C_n and one or more termini distal to the C_n, wherein the termini distal to the C_n each comprise —

C_xH_y, wherein x is an integer and 8≦

x≦

24, and y is an integer and 1≦

y≦

2x+1;

a is an integer, 1≦

a≦

5;

2≦

b+a≦

6; and

each A is covalently bonded to the C_n through 1 or 2 carbon-carbon, carbon-oxygen, or carbon-nitrogen bonds,

wherein the vesicle wall comprises at least about 50 mol % the substituted fullerene.

13. The method of claim 12, wherein the wall is a bilayer membrane.

14. The method of claim 12, wherein the wall is a monolayer membrane.

15. The method of claim 12, wherein from about 0.01 mole % to about 100 mole % of the substituted fullerene molecules further comprise a functional group covalently linked to a B group.

16. The method of claim 15, wherein the functional group is selected from the group consisting of biotin-containing moieties, antigen-binding moieties, and tissue-recognition moieties.

17. The method of claim 12, wherein the wall comprises at least about 75 mol % a substituted fullerene having structure I.

18. The method of claim 12, wherein the therapeutic agent is an anti-cancer drug.

19. The method of claim 12, further comprising

(ii) administering an adjuvant to the mammal, wherein the adjuvant facilitates recognition of the tissue by a functional group, if any, covalently bonded to the substituted fullerene in the layer of the wall adjacent to the vesicle exterior;

union of the vesicle with the membrane of a cell of the tissue;

or both.

20. The method of claim 12, further comprising:

(ii) disaggregating the vesicle.

21. A method of reversibly forming a vesicle having an interior, an exterior, and a wall, wherein the wall comprises one or more layers and the interior of the vesicle, a portion of the wall between two layers, or both comprise a therapeutic agent, comprising:

dissolving in an aqueous solvent (a) a substituted fullerene having the structure I;

(B)_b—

C_n-(A)_a 

 

(I)

wherein C_n is a fullerene moiety comprising n carbon atoms, wherein n is an integer and 60≦

n≦

240;

B is an organic moiety comprising from 1 to about 40 polar headgroup moieties;

b is an integer and 1≦

b≦

5;

each B is covalently bonded to the C_n through 1 or 2 carbon-carbon, carbon-oxygen, or carbon-nitrogen bonds;

A is an organic moiety comprising a terminus proximal to the C_n and one or more termini distal to the C_n, wherein the termini distal to the C_n each comprise —

C_xH_y, wherein x is an integer and 8≦

x≦

24, and y is an integer and 1≦

y≦

2x+1;

a is an integer, 1≦

a≦

5;

2≦

b+a≦

6; and

each A is covalently bonded to the C_n through 1 or 2 carbon-carbon, carbon-oxygen, or carbon-nitrogen bonds, and

(b) the therapeutic agent,

wherein the pH of the solvent is sufficiently low to form a vesicle from the substituted fullerene and the vesicle comprise at least 50 mole % of the fullerene.

22. The method of claim 21, wherein the wall is a bilayer membrane.

23. The method of claim 21, wherein the wall is a monolayer membrane.

24. The method of claim 21, wherein the pH is less than about 8.0.

25. The method of claim 21, further comprising disaggregating the vesicle.