Hyperbranched polymeric micelles for encapsulation and delivery of hydrophobic molecules

• US 6,328,988 B1
• Filed: 10/21/1999
• Issued: 12/11/2001
• Est. Priority Date: 04/23/1999
• Status: Expired due to Fees

• Current Assignee: Rutgers University
• Original Assignee: Rutgers University
• Inventors: Uhrich, Kathryn E.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): FUBARA, BLESSING M
• Application Number:
  US09/422,295
• Time in Patent Office: 782 Days
• Field of Search: 514/773, 514/937, 514/969, 424/501, 424/450, 424/451, 424/489, 424/78.08
• US Class Current: 424/422
• CPC Class Codes: A61K 47/6907 the form being a microemulsion, nanoemulsion or micelle
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/5146 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: C08G 83/005 Hyperbranched macromolecules
• CPC Class Codes: C08L 71/02 Polyalkylene oxides
• CPC Class Codes: G03C 1/04 with macromolecular additives; with layer-forming substances
• CPC Class Codes: G03C 5/3056 Macromolecular additives G03C5/261 takes precedence

Abstract

Polymeric micelles for encapsulation of hydrophobic molecules are provided. Methods and formulations for delivering hydrophobic molecules to a host via these micelles are also provided. Methods of stabilizing liposomes or lipid based formulations by addition of polymeric micelles are also provided.

Claims

1. A hydrophobic molecule encapsulated in a polymer, said polymer having a structure selected from the group consisting of:

2. The encapsulate of claim 1, wherein said hydrophobic molecule has biological or pharmaceutical activity.

3. The encapsulate of claim 1, wherein said hydrophobic molecule is a fragrance, dye, protein or vitamin.

4. The encapsulate of claim 1, having the structure R(—

O—

R₁)_x, wherein R(—

O—

)_x, is a polyol moiety.

5. The encapsulate of claim 4, wherein said polyol moiety is a 1,1,1-tris(hydroxyphenyl)ethane moiety.

6. The encapsulate of claim 4, wherein all of said hydroxyl groups of said dicarboxylic acid moiety are acylated with carboxylic acids having from 6 to 24 carbon atoms.

7. The encapsulate of claim 6, wherein y is 0.

8. The encapsulate of claim 6, wherein said divalent dicarboxylic acid moiety is a mucic acid moiety.

9. The encapsulate of claim 1, wherein said poly(alkylene oxide) is a methoxy-terminated poly(ethylene glycol) and Q is —

NH—

.

10. A formulation comprising the encapsulate of claim 1, and an acceptable vehicle.

11. The formulation of claim 10, wherein the accetable vehicle comprises an aqueous solution, suspension, dispersion, emollient, lotion, cream, salve, balm or ointment.

12. The formulation of claim 10, wherein the concentration of said encapsulate in said formulation is between about 10⁻

10 M and 10⁶ M.

13. The formulation of claim 12, wherein said encapsulate concentration is between about 10⁻

8 M and about 10⁶ M.

14. The formulation of claim 10, wherein the hydrophobic molecule of the encapsulate has biological or pharmaceutical activity.

15. The formulation of claim 10, wherein the hydrophobic molecule of the encapsulate is a dye, fragrance, protein, or vitamin.

16. A method of delivering a hydrophobic molecule to a host comprising administering to the host an encapsulate of claim 1.

17. The method of claim 16, wherein the host is an animal and the encapsulate is administered orally, subcutaneously, intramuscularly, intraperitoneally or intravenously.

18. The method of claim 16, wherein the encapsulate is administered topically to the host.

19. The method of claim 16, wherein the hydrophobic molecule of the encapsulate is biologically or pharmaceutically active.

20. The encapsulate of claim 1 wherein R(—

O—

)_x is an aliphatic polyol having from 1 to 10 carbon atoms.

21. The encapsulate of claim 1 wherein R(—

O—

)_x is a cycloaliphatic polyol.

22. The encapsulate of claim 21 wherein the cycloaliphatic polyol is a sugar.

23. The encapsulate of claim 1 wherein R(—

O—

)_x is an aromatic polyol.

24. The encapsulate of claim 23 wherein the aromatic polyol is 1,1,1-tris(4′

-hydroxyphenyl)ethane, 1,3-adamantanediyl)diphenol, 2,6-bis(hydroxyalkyl)cresol, 2,2′

-alkylene-bis(6-tert-butyl-4-alkylphenol), 2-2′

-alkylene-bis(t-butylphenol), catechol, an alkylcatechol, pyrogallol, fluoroglycinol, 1,2,4-benzenetriol, resorcinol, an alkylresorcinol, a dialkylresorcinol, orcinol monohydrate, olivetol, hydroquinone, an alkylhydroquinone, 1,1-bi-2-naphthol, a phenyl hydroquinone, a dihydroxynaphthalene, 4,4′

-(9-fluorenylidene)-diphenol, anthrarobin, dithranol, bis(hydroxyphenyl) methane a biphenol, a dialkylstilbeterol, a bis(hydroxyphenyl) alkane, or bisphenol-A.

25. The encapsulate of claim 1 wherein R(—

O—

)_x is a cyclic crown ether, a cyclodextrine, or a dextrine.

26. The encapsulate of claim 1 wherein the polymer has a number average molecular weight between about 1,000 and about 100,000 daltons.

27. The encapsulate of claim 1 wherein the polymer has a number average molecular weight between about 2,500 and about 25,000 daltons.