Encapsulation and separation of charged organic solutes inside catanionic vesicles

• US 20080305157A1
• Filed: 06/09/2008
• Published: 12/11/2008
• Est. Priority Date: 06/08/2007
• Status: Abandoned Application

• Current Assignee: University of Maryland Office of Technology Commercialization
• Original Assignee: University of Maryland Office of Technology Commercialization
• Inventors: English, Douglas S., DeShong, Philip R., Danoff, Emily J., Lee, Jaeho, Wang, Xiang, Raghavan, Srinivasa
• Application Number:
  US12/155,758
• Publication Number:
  US 20080305157A1
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543

Abstract

Catanionic vesicles including solute ion, methods for forming these, and methods of using these.

Claims

1. A method for sequestering a solute ion within a catanionic vesicle comprising:

determining the charge of the solute ion;

creating a catanionic vesicle having a net surface charge opposite to the charge of the solute ion;

combining the catanionic vesicle with the solute ion; and

allowing the catanionic vesicle to sequester the solute ion.

2. The method of claim 1, wherein the solute ion is in solution, comprising:

adding a cationic surfactant and an anionic surfactant to the solution, in a ratio effective to produce the catanionic vesicles.

3. The method of claim 2, wherein the solute ion is selected from the group consisting of a biologically active compound, a pharmaceutical agent, a fluorescently active chemical, a cosmetic chemical, an agriculturally active chemical, a fertilizer, a nutrient, a pesticide, an herbicide, and combinations.

4. The method of claim 1, wherein the solute ion is in a bulk solution, and the catanionic surfactant vesicle comprises a bilayer comprising a cationic surfactant and an anionic surfactant, and an inner pool separated from the bulk solution by the bilayer, the method comprising:

combining the catanionic surfactant vesicle with the bulk solution and sequestering the solute ion in the inner pool and/or the bilayer of the catanionic vesicle, and

separating the solute ion from the bulk solution by separating the catanionic surfactant vesicle from the bulk solution.

5. The method of claim 4, wherein the solute ion is selected from the group consisting of an atomic ion, a charged inorganic molecule, and a charged organic molecule.

6. The method of claim 4 wherein the separating comprises size exclusion chromatography, affinity chromatography, and/or electrokinetic chromatography.

7. An aqueous composition, comprising,

an aqueous environment and a catanionic surfactant vesicle,

the catanionic surfactant vesicle comprising

a bilayer comprising a cationic surfactant and an anionic surfactant and having a net surface charge;

an inner pool separated from the aqueous environment by the bilayer;

a solute ion having a charge, within the inner pool and/or the bilayer;

the net surface charge of the bilayer being opposite to that of the solute ion.

8. The aqueous composition of claim 7, wherein the solute ion is selected from the group consisting of a metal, carboxyfluorescein, Lucifer yellow, Rhodamine 6G, Sulforhodamine 101, a drug, doxorubicin, a chemotherapeutic agent, a natural product, a peptide, an oligopeptide, a polypeptide, a nucleotide, an oligonucleotide, a polynucleotide, DNA, RNA, derivatives of these, and combinations.

9. The aqueous composition of claim 7, wherein the anionic surfactant is selected from the group consisting of alkyl sulfate, sodium octyl sulfate, sodium decyl sulfate, sodium dodecyl sulfate, sodium tetra-decyl sulfate, alkyl sulfonates, sodium octyl sulfonate, sodium decyl sulfonate, sodium dodecyl sulfonate, alkyl benzene sulfonates, sodium octyl benzene sulfonate, sodium decyl benzene sulfonate, sodium dodecyl benzene sulfonate, fatty acid salt, sodium octanoate, sodium decanoate, sodium dodecanoate, sodium salt of oleic acid, derivatives of these, and combinations.

10. The aqueous composition of claim 7, wherein the cationic surfactant is selected from the group consisting of alkyl trim ethylammonium halide, octyl trimethylammonium bromide, decyl trimethylammonium bromide, dodecyl trimethylammonium bromide, myristyl trimethylammonium bromide, cetyl trimethylammonium bromide, alkyl trimethylammonium tosylate, octyl trimethylammonium tosylate, decyl trimethylammonium tosylate, dodecyl trimethylammonium tosylate, myristyl trimethylammonium tosylate, cetyl trimethylammonium tosylate, N-alkyl pyridinium halide, decyl pyridinium chloride, dodecyl pyridinium chloride, cetyl pyridinium chloride, derivatives of these and combinations.

11. The aqueous composition of claim 7, wherein the cationic and/or the anionic surfactant is selected from the group consisting of SDS, DTAC, DTAB, DPC, DDAO, DDAB, SOS, AOT, derivatives of these, and combinations.

12. The aqueous composition of claim 7, wherein the cationic surfactant is a single alkyl chain surfactant and/or the anionic surfactant is a single alkyl chain surfactant.

13. The aqueous composition of claim 7,

wherein the solute ion is a cation having positive charge and

wherein the cationic surfactant and anionic surfactant comprising the bilayer are in proportions creating a bilayer with a negative net surface charge.

14. The aqueous composition of claim 7,

wherein the solute ion is an anion having negative charge and

wherein the cationic surfactant and anionic surfactant comprising the bilayer are in proportions creating a bilayer with a positive net surface charge

15. The aqueous composition of claim 7,

wherein the bilayer comprises cationic surfactant and anionic surfactant in a molar ratio in a range of from about 1:

9 to about 9;

1, excluding a molar ratio of about 1;

1.

16. The aqueous composition of claim 7, wherein the combined weight percentage of cationic surfactant and anionic surfactant in the external aqueous environment is less than about 5 wt %.

17. The aqueous composition of claim 7, wherein the combined weight percentage of cationic surfactant and anionic surfactant in the external aqueous environment is less than from about 0.0001 wt % to about 3 wt %.

18. The aqueous composition of claim 7, wherein the combined weight percentage of cationic surfactant and anionic surfactant in the external aqueous environment is from about 0.5 wt % to about 2 wt %.

19. The aqueous composition of claim 7, wherein the concentration of the solute ion within the catanionic vesicle is greater than the concentration of the solute ion in the aqueous environment.

20. The aqueous composition of claim 7, wherein the encapsulation efficiency of the solute ion in the vesicle is at least about 2%.

21. The aqueous composition of claim 7, wherein the percentage of solute adsorbed on the bilayer is at least about 0.5%.

22. A method of introducing an agent into a cell, comprising:

contacting the cell with a composition comprising catanionic surfactant vesicles comprising a bilayer of a cationic surfactant and an anionic surfactant defining an inner pool comprising the agent, the net surface charge of the bilayer being opposite to that of the agent.

23. The method of claim 22, wherein the cell is within a living organism.

24. The method of claim 22, wherein the composition comprising the catanionic surfactant vesicles is administered orally or intravenously.

25. A method of introducing a nucleic acid into a cell, comprising:

administering catanionic surfactant vesicles comprising a nucleic acid to the cell,

wherein the catanionic surfactant vesicle comprises

a bilayer comprising a cationic surfactant and an anionic surfactant,

an inner pool separated from an aqueous environment by the bilayer,

the inner pool and/or the bilayer comprising the nucleic acid,

the nucleic acid having a negative charge,

the cationic surfactant and anionic surfactant comprising the bilayer having a net positive surface charge.

26. A kit, comprising:

a premeasured amount of an anionic surfactant in a first labeled container; and

a premeasured amount of a cationic surfactant in a second labeled container,

wherein the premeasured amount of the anionic surfactant and the premeasured amount of the cationic surfactant are selected so that when the premeasured amount of the anionic surfactant and the premeasured amount of the cationic surfactant are added to a predetermined amount of water containing a solute ion having a charge, catanionic surfactant vesicles are formed and

wherein the catanionic surfactant vesicles comprise

a bilayer comprising a cationic surfactant and an anionic surfactant and having a net surface charge,

an inner pool separated from the aqueous environment by the bilayer,

the solute ion within the inner pool and/or the bilayer, and

the net surface charge of the bilayer being opposite to that of the solute ion.

27. A kit, comprising:

a mixture of an anionic surfactant and a cationic surfactant in a labeled container,

wherein the anionic surfactant and the cationic surfactant are in a predetermined molar ratio in the mixture,

wherein the predetermined molar ratio is selected so that when the mixture is added to a predetermined amount of water containing a solute ion having a charge, catanionic surfactant vesicles are formed and

wherein the catanionic surfactant vesicles comprise

a bilayer comprising a cationic surfactant and an anionic surfactant and having a net surface charge,

an inner pool separated from the aqueous environment by the bilayer,

the solute ion within the inner pool and/or the bilayer, and

the net surface charge of the bilayer being opposite to that of the solute ion.

28. A kit, comprising:

a mixture of an anionic surfactant, a cationic surfactant, and a solute ion having a charge in a labeled container,

wherein the anionic surfactant and the cationic surfactant are in a predetermined molar ratio in the mixture,

wherein the predetermined molar ratio is selected so that when the mixture is added to a predetermined amount of water, catanionic surfactant vesicles are formed and

wherein the catanionic surfactant vesicles comprise

a bilayer comprising a cationic surfactant and an anionic surfactant and having a net surface charge,

an inner pool separated from the aqueous environment by the bilayer,

the solute ion within the inner pool and/or the bilayer, and

the net surface charge of the bilayer being opposite to that of the solute ion.