VESICLES OF SELF-ASSEMBLING BLOCK COPOLYMERS AND METHODS FOR MAKING AND USING THE SAME

• US 20100003336A1
• Filed: 11/30/2007
• Published: 01/07/2010
• Est. Priority Date: 12/01/2006
• Status: Abandoned Application

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Deming, Timothy J., Holowka, Eric P., Sun, Victor Z., Kamei, Daniel T.
• Application Number:
  US12/517,009
• Publication Number:
  US 20100003336A1
• Time in Patent Office: Days
• US Class Current: 424/491
• CPC Class Codes: A61K 9/1273 Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances polymers grafted or coated on phosphatidyl liposomes A61K9/1271, on non-phosphatidyl liposomes A61K9/1272
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Vesicles of self-assembling block copolymers, e.g., diblock copolypeptides, as well as methods of making and using the same. Vesicles of the invention have a shell made up of block copolymers that include an intracellular transduction hydrophilic domain and a hydrophobic domain. In certain embodiments, the vesicles include an encapsulated active agent, e.g., a diagnostic or therapeutic agent. The vesicles find use in a variety of different application, including the intracellular delivery of active agents, e.g., diagnostic and therapeutic agents.

Claims

1. A vesicle comprising a shell encapsulating a polar fluid medium, wherein said shell comprises self-assembling block copolymers that include a first hydrophobic domain and a second hydrophilic intracellular transduction domain.

2. The vesicle according to claim 1, wherein said shell comprises a single type of self-assembling block copolymer.

3. The vesicle according to claim 1, wherein said shell comprises two or more different types of self-assembling block copolymers.

4. The vesicle according to Claim 1, wherein said self assembling block copolymer is a block copolypeptide.

5. The vesicle according to claim 4, wherein said first hydrophobic domain is a homopolypeptidic domain.

6. The vesicle according to claim 5, wherein said first hydrophobic domain ranges in length from about 10 to about 30 residues.

7. The vesicle according to claim 6, wherein said first hydrophobic domain is a poly-leucine (polyL) domain.

8. The vesicle according to claim 7, wherein said polyL domain is L₂₀.

9. The vesicle according to claim 4, wherein said hydrophilic domain is a heteropolypeptidic domain.

10. The vesicle according to claim 9, wherein said hydrophilic domain is a homopolypeptidic domain.

11. The vesicle according to claim 10, said hydrophilic domain ranges in length from about 40 to about 80 residues.

12. The vesicle according to claim 11, wherein hydrophilic domain is a poly arginine (polyR) domain.

13. The vesicle according to claim 12, wherein said polyr domain is R₆₀.

14. The vesicle according to Claim 1, wherein said self-assembling block copolymer is a diblock copolypeptide, wherein said second domain has a length that is about 2 to 4 times longer than the length of said first domain.

15. The vesicle according to claim 14, wherein said diblock copolypeptide is a R₆₀L₂₀.

16. The vesicle according to claim 1, wherein said vesicle has a diameter ranging from about 50 to about 1000 nm.

17. The vesicle according to claim 1, wherein said vesicle is stable at temperatures up to about 80°

C.

18. The vesicle according to claim 1, wherein said vesicle is non-toxic.

19. The vesicle according to claim 1, wherein said polar fluid medium is an aqueous medium.

20. The vesicle according to claim 19, wherein said aqueous medium comprises a water-soluble active agent.

21. The vesicle according to claim 20, wherein said water-soluble active agent is a diagnostic agent.

22. The vesicle according to claim 20, wherein said water-soluble active agent is a therapeutic agent.

23. A composition comprising a plurality of vesicles according to claim 1.

24. The composition according to claim 23, wherein said composition exhibits low size polydispersity with respect to vesicles present therein.

25. The composition according to claim 23, wherein said vesicles comprise an active agent.

26. The composition according to claim 25, wherein said composition is a pharmaceutical composition.

27. A method for preparing a vesicle according to claim 1, said method comprising;

(a) providing a mixture of fluid polar medium comprising self-assembling block copolymers that include a first hydrophobic domain and a second hydrophilic intracellular transduction domain; and

(b) maintaining said mixture under conditions sufficient to produce said vesicle.

28. The method according to claim 27, wherein said fluid polar medium is an aqueous medium.

29. The method according to claim 28, wherein said aqueous medium comprises a water-soluble active agent.

30. A method of treating or preventing a disease in a subject, said method comprising administering to the subject vesicle according to claim l.

31. A self-assembling block copolymer capable of forming a vesicle encapsulating a polar fluid medium, said self-assembling block copolymer comprising a first hydrophobic domain and a second hydrophilic intracellular transduction domain.

32. The self-assembling block polymer according to claim 31, wherein said block copolyner is a block copolypeptide.

33. The self-assembling block copolymer according to claim 32, wherein said first hydrophobic domain is a homopolypeptidic domain.

34. The self-assembling block copolymer according to claim 33, wherein said first hydrophobic domain ranges in length from about 10 to about 30 residues.

35. The self-assembling block copolymer according to claim 34, wherein said first hydrophobic domain is a poly-leucine (polyL) domain.

36. The self-assembling block copolymer according to claim 35, wherein said polyL domain is L₂₀.

37. The self-assembling block copolymer according to claim 32, wherein said hydrophilic domain is a heteropolypeptidic domain.

38. The self-assembling block copolymer according to claim 37, wherein said hydrophilic domain is a homopolypeptidic domain.

39. The self-assembling block copolymer according to claim 38, said hydrophilic domain ranges in length from about 40 to about 80 residues

40. The self-assembling block copolymer according to claim 39, wherein hydrophilic domain is a poly arginine (polyR) domain.

41. The self-assembling block copolymer according to claim 40, wherein said polyR domain is R₆₀.

42. The self-assembling block copolymer according to claim 31, wherein said self-assembling block copolymer is a diblock copolypeptide, wherein said second domain has a length that is about 2 to 4 times longer than the length of said first domain.

43. The self-assembling block copolymer according to claim 42, wherein said diblock copolypeptide is a R₆₀L₂₀.