Materials and methods for drug delivery and uptake

• US 7,090,868 B2
• Filed: 09/13/2002
• Issued: 08/15/2006
• Est. Priority Date: 09/13/2002
• Status: Expired due to Fees

• Current Assignee: University of Florida (State University System of Florida)
• Original Assignee: University of Florida (State University System of Florida)
• Inventors: Gallup, Allison, Gower, Laurie A., Sheth, Piyush, Ossenbeck, Michael, Patel, Vishal M.
• Primary Examiner(s): Lankford, Jr., Leon B.
• Assistant Examiner(s): Barnhart, Lora E
• Application Number:
  US10/243,340
• Publication Number:
  US 20040052865A1
• Time in Patent Office: 1,432 Days
• Field of Search: 424/400, 424/450, 424/458, 424/489, 424/490, 424/686
• US Class Current: 424/489
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61K 9/501 Inorganic compounds

Abstract

The subject invention pertains to novel materials and methods for use in delivering and sequestering substances, such as pharmacological agents, within a patient. One aspect of the invention is directed towards core-shell particles having a core encapsulated within a calcium carbonate shell, with an intermediate layer composed of an amphiphilic compound surrounding the core. When the particles of the subject invention are administered to a patient, they are capable of removing lipophilic drugs by absorption of the drug through their mineral shell and into their core. The particles of the subject invention can also be administered to a patient as controlled release, drug delivery vehicles. Thus, in another aspect, the subject invention concerns a method of delivering pharmacological agents by administering the core-shell particles of the subject invention to a patient in need of such administration.

Claims

1. A core-shell particle comprising:

(a) a shell, wherein said shell comprises a continuous calcium carbonate film that is not an aggregate of individual calcium carbonate crystals;

(b) a core; and

(c) an intermediate layer between said shell and said core, wherein said intermediate layer comprises an amphiphilic compound, and wherein said core and said intermediate layer are surrounded by said shell.

2. The core-shell particle of claim 1, wherein said core is hollow.

3. The core-shell particle of claim 1, wherein said core comprises a lipophilic liquid.

4. The core-shell particle of claim 3, wherein said lipophilic liquid is an oil.

5. The core-shell particle of claim 4, wherein said oil comprises dodecane.

6. The core-shell particle of claim 3, wherein said lipophilic liquid is selected from the group consisting of cyclohexane, n-hexane, benzene, cottonseed oil, rapeseed oil, squalane, squalene, waxes, styrene, divinylbenzene, butyl acrylate, 2-ethylhexyl acrylate, cyclohexyl acrylate, decyl acrylate, lauryl acrylate, dodecenyl acrylate, myristyl acrylate, palmityl acrylate, hexadecenyl acrylate, stearyl acrylate, octadecenyl acrylate, behenyl acrylate, butyl methacrylate, 2-ethylhexyl methacrylate, cyclohexyl methacrylate, decyl methacrylate, lauryl methacrylate, dodecenyl methacrylate, myristyl methacrylate, palmityl methacrylate, hexadecenyl methacrylate, stearyl methacrylate, octadecenyl methacrylate, behenyl methacrylate, and silicone macromonomers.

7. The core-shell particle of claim 1, wherein said amphiphilic compound has a partially deprotonated carboxylic acid headgroup functionality.

8. The core-shell particle of claim 1, wherein said amphiphilic compound is selected from the group consisting of stearic acid and arachidic acid.

9. The core-shell particle of claim 1, wherein said intermediate layer comprises a film of said amphiphilic compound.

10. The core-shell particle of claim 1, wherein said intermediate layer comprises a monolayer of said amphiphilic compound.

11. The core-shell particle of claim 1, wherein said shell is porous.

12. The core-shell particle of claim 1, wherein said shell has a diameter within the range of about 1 μ

m to about 100 μ

m in diameter.

13. The core-shell particle of claim 1, wherein said shell has a diameter within the range of about 1 μ

m to about 50 μ

m in diameter.

14. The core-shell particle of claim 1, wherein said shell has a diameter within the range of about 1 μ

m to about 5 μ

m in diameter.

15. The core-shell particle of claim 1, wherein said shell has a thickness within the range of about 200 nm to about 500 nm in thickness.

16. The core-shell particle of claim 1, wherein said shell has a thickness within the range of about 100 nm to about 1000 nm in thickness.

17. The core-shell particle of claim 1, wherein said intermediate layer comprises stearic acid.

18. The core-shell particle of claim 1, wherein said shell is a sphere.

19. The core-shell particle of claim 1, wherein said core and said intermediate layer are together an emulsion.

20. The core-shell particle of claim 1, wherein said core comprises a biologically active agent.

21. The core-shell particle of claim 3, wherein said core further comprises a biologically active agent.

22. The core-shell particle of claim 20, wherein said biologically active agent is selected from the group consisting of medicaments, vitamins, and mineral supplements.

23. The core-shell particle of claim 20, wherein said biologically active agent is selected from the group consisting of antifungal agents, antibacterial agents, anti-viral agents, anti-parasitic agents, growth factors, angiogenic factors, anaesthetics, mucopolysaccharides, metals, antibodies, antibody fragments, and cells.

24. The core-shell particle of claim 20, wherein said biologically active agent is a lipophilic drug.

25. The core-shell particle of claim 24, wherein said lipophilic drug comprises a tricyclic anti-depressant selected from the group consisting of amitriptyline, clomipramine, desipramine, imipramine, norclomipramine, nortriptyline, and trimipramine.

26. The core-shell particle of claim 1, wherein said core comprises a catabolic enzyme.

27. The core-shell particle of claim 3, wherein said core further comprises a catabolic enzyme.

28. The core-shell particle of claim 27, wherein said catabolic enzyme is a cytochrome P450 enzyme.

29. The core-shell particle of claim 28, wherein said cytochrome P450 enzyme is selected from the group consisting of CYP1A2, CYP2A6, CYP286, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4.

30. The core-shell particle of claim 1, wherein said continuous calcium carbonate film has a uniform thickness.

31. The core-shell particle of claim 1, wherein said continuous calcium carbonate film has a spherulitic crystal structure.

32. The core-shell particle of claim 1, wherein said continuous calcium carbonate film has a spherulitic crystalline structure that exhibits a Maltese Cross extinction pattern when viewed under cross-polarized light microscopy.

33. The core-shell particle of claim 32, wherein said continuous calcium carbonate film has a uniform thickness.

34. The core-shell particle of claim 1, wherein said continuous calcium carbonate film is smooth.

35. A core-shell particle comprising:

(a) a shell, wherein said shell comprises a continuous calcium carbonate film, wherein said film is not an aggregate of individual calcium carbonate crystals, wherein said film is formed by a liquid phase calcium carbonate precursor that confers on said film a uniform thickness and an amorphous or spherulitic crystalline structure, and wherein said spherulitic crystalline structure exhibits a Maltese Cross extinction pattern when viewed under cross-polarized light microscopy;

(b) a core; and

(c) an intermediate layer between said shell and said core, wherein said intermediate layer comprises an amphiphilic compound, and wherein said core and said intermediate layer are surrounded by said shell.