Method for Nanoencapsulation

• US 20100303913A1
• Filed: 10/31/2006
• Published: 12/02/2010
• Est. Priority Date: 10/31/2006
• Status: Active Grant

• Current Assignee: Rice University
• Original Assignee: Rice University
• Inventors: Fang, Yu-Lun, Gheith, Muhammed K., Wong, Michael S.
• Granted Patent: US 8,663,690 B2
• Time in Patent Office: Days
• US Class Current: 424/488
• CPC Class Codes: A61K 9/5089 Processes
• CPC Class Codes: A61K 9/5169 Proteins, e.g. albumin, gelatin
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Methods of nanoencapsulation are described herein. Embodiments of the method utilize the coacervation of a cationic polyelectrolyte with an anionic polyelectrolyte to form a novel capsular matrix. In particular, the novel methods may be used to encapsulate a suspension of a hydrophobic material such as a carotenoid. The disclosed methods do not require lengthy pH adjustments nor do they require the use of any toxic crosslinking agents. In one embodiment, a method of encapsulation comprises dispersing a hydrophobic compound in an organic solvent to form a solution. The method also comprises admixing an anionic polyelectrolyte and a cationic polyelectrolyte with the suspension to form a mixture. In addition, the method comprises quiescently cooling the mixture so as to cause self-crosslinking of a capsular matrix encapsulating the hydrophobic particles.

Claims

1. A method of encapsulation comprising:

a) admixing a hydrophobic compound in an organic solvent to form a mixture;

b) admixing an anionic polyelectrolyte and a cationic polyelectrolyte with the mixture to form a suspension of encapsulated hydrophobic particles;

c) quiescently cooling the suspension so as to cause self-crosslinking of the encapsulated hydrophobic particles to form a capsular matrix.

2. The method of claim 1, wherein step (a) comprises admixing an amount of said hydrophobic compound in said organic solvent at a concentration greater than the saturation point of said organic solvent so as to form a mixture comprising a solution of the hydrophobic compound and a suspension of undissolved hydrophobic particles.

3. The method of claim 1 wherein said mixture is a solution.

4. The method of claim 1 wherein said mixture is an emulsion.

5. The method of claim 1 wherein said mixture is a suspension.

6. The method of claim 1 wherein step (b) comprises admixing the anionic polyelectrolyte before the cationic polyelectrolyte.

7. The method of claim 1 wherein step (b) comprises admixing the cationic polyelectrolyte before the anionic polyelectrolyte.

8. The method of claim 1 wherein step (b) comprises admixing the cationic polyelectrolyte and the anionic polyelectrolyte simultaneously.

9. The method of claim 1 wherein step (b) comprises admixing the cationic polyelectrolyte and the anionic polyelectrolyte at a cationic polyelectrolyte to anionic polyelectrolyte weight ratio of at least 2:

1.

10. The method of claim 1 wherein step (a) comprises dispersing the hydrophobic compound at a temperature ranging from 40°

C. to 80°

C.

11. The method of claim 1 wherein step (b) comprises admixing the anionic polyelectrolyte and the cationic polyelectrolyte at a temperature ranging from 40°

C. to 60°

C.

12. The method of claim 1 wherein step (c) comprises cooling the mixture to a temperature ranging from 20°

C. to 30°

C.

13. The method of claim 1 wherein step (c) comprises cooling the mixture at a pH ranging from 5 to 6.

14. The method of claim 1 further comprising adjusting the pH of the mixture after step (b).

15. The method of claim 1 further comprising dissolving the capsular matrix in water at a temperature ranging from 40°

C. to 60°

C. to form a suspension of capsules having an average diameter ranging from 1 nm to 1000 nm.

16. The method of claim 1 wherein the cationic polyelectrolyte is a gelatin.

17. The method of claim 1 wherein the cationic polyelectrolyte comprises chitosan, whey protein, albumin, beta-lactoglobulin, potato protein, faba bean legumin, soybean protein, or combinations thereof.

18. The method of claim 1 wherein the anionic polyelectrolyte is gum arabic.

19. The method of claim 1 wherein the anionic polyelectrolyte comprises any anionic polysaccharide, alginate, pectin, agar, carrageenan, or combinations thereof.

20. The method of claim 1 wherein the hydrophobic compound comprises a carotenoid.

21. The method of claim 20 wherein the carotenoid comprises lutein, antheraxanthin, astaxanthin, canthaxanthin, a-carotene, beta-carotene, cryptoxanthin, diatoxanthin, fucoxanthin, fucoxanthinol, lactucaxanthin, lycopene, neoxanthin, neurosporene, peridinin, phytoene, rhodopin, siphonaxanthin, spheroidene, spirilloxanthin, uriolide, uriolide acetate, violaxanthin, zeaxanthin, or combinations thereof.

22. The method of claim 1 wherein the hydrophobic compound is selected from the group consisting of phytosterols and coenzymes Q.

23. The method of claim 1 wherein the encapsulated hydrophobic particles have an average diameter ranging from about 1 nm to about 1000 nm.

24. The method of claim 1 wherein the organic solvent comprises an alcohol.

25. The method of claim 1 wherein the hydrophobic compound is an oil.

26. The method of claim 1, further comprising adding a binder to the capsular matrix to dissolve the capsular matrix.

27. The method of claim 25, further comprising grinding the capsular matrix into a powder.

28. The method of claim 25 wherein the binder is a salt.

29. The method of claim 28 wherein the binder comprises calcium chloride, sodium chloride, sodium bicarbonate, sodium sulfate, calcium carbonate, magnesium sulfate, starch or combinations thereof.

30. The method of claim 27 wherein said powder is soluble in warm water.

31. The method of claim 27 wherein said powder is soluble in cold water.

32. A capsular matrix comprising:

a self-crosslinked network of capsules encapsulating a plurality of hydrophobic particles, wherein each capsule comprises a cationic polyelectrolyte and an anionic polyelectrolyte.

33. The capsular matrix of claim 32 wherein said self-crosslinked network of capsules is water-soluble.

34. The capsular matrix of claim 32 wherein said cationic polyelectrolyte comprises gelatin.

35. The capsular matrix of claim 32 wherein said anionic polyelectrolyte comprises gum arabic.