Polymerized liposomes targeted to M cells and useful for oral or mucosal drug delivery

• US 6,387,397 B1
• Filed: 06/02/1999
• Issued: 05/14/2002
• Est. Priority Date: 04/18/1997
• Status: Expired due to Fees

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Chen, Hongming, Langer, Robert S.
• Primary Examiner(s): Kishore, Gollamudi S.
• Application Number:
  US09/324,458
• Time in Patent Office: 1,077 Days
• Field of Search: 424/450, 424/812, 424/1.21, 424/9.321, 424/9.51, 424/417, 436/829, 935/54, 428/402.2
• US Class Current: 424/450
• CPC Class Codes: A61K 2039/541 Mucosal route
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/05 Actinobacteria, e.g. Actinomyces, Streptomyces, Nocardia, Bifidobacterium, Gardnerella, Corynebacterium; Propionibacterium Mycobacterium A61K39/04
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• 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: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
• CPC Class Codes: Y10S 436/829 Liposomes, e.g. encapsulation
• CPC Class Codes: Y10T 428/2984 Microcapsule with fluid core [includes liposome]

Abstract

The present invention relates to targeted polymerized liposomes for oral and/or mucosal delivery of vaccines, allergens and therapeutics. In particular, the present invention relates to polymerized liposomes which have been modified on their surface to contain a molecule or ligand which targets the polymerized liposome to a specific site or cell type. More particularly, the invention relates to the use of polymerized liposomes modified to contain a carbohydrate or lectin on their surface.

Claims

1. A polymerized liposome comprising a phospholipid bilayer having phospholipids covalently bonded to each other, an antigen, an adjuvant, and a targeting molecule, wherein the targeting molecule is Ulex Europeans Agglutinin I.

14. The polymerized liposome of claim 1, 2, 9 or 10 wherein the antigen is an influenza antigen, an HTLV antigen, a rhinovirus antigen, a herpes virus antigen, or an Epstein-Barr virus antigen.

15. The polymerized liposome of claim 1 in which the antigen is and the adjuvant are in the interior space of the polymerized liposome.

17. The polymerized liposome of claim 1 in which the antigen is in the interior space of the polymerized liposome and the adjuvant is in the bilayer of the polymerized liposome.

19. The polymerized liposome of claim 1 in which the antigen and the adjuvant are in the bilayer of the polymerized liposome.

21. The polymerized liposome of claim 1 in which the antigen is in the bilayer of the polymerized liposome and the adjuvant is in the interior space of the polymerized lipsome.

23. The polymerized liposome of claim 1, 2, 8 or 9 in which the antigen is hydrophobic.

24. The polymerized liposome of claim 1, 2, 8 or 9 in which the phospholipid is DODPC.

25. The polymerized liposome of claim 1, 2, 8 or 9 having a degree of crosslinking between 30 and 100 percent.

2. A polymerized liposome suitable for oral delivery of an antigen to a mammal, said polymerized liposome comprising a phospholipid bilayer having phospholipids that are covalently bonded to each other, an antigen, and a targeting molecule, wherein the targeting molecule is a lectin which specifically binds to fucosyl sugars.

12. The polymerized liposome of claim 2, 8 or 9 further comprising an adjuvant.

16. The polymerized liposome of claim 12 in which the antigen is and the adjuvant are in the interior space of the polymerized liposome.

18. The polymerized liposome of claim 12 in which the antigen is in the interior space of the polymerized liposome and the adjuvant is in the bilayer of the polymerized liposome.

20. The polymerized liposome of claim 12 in which the antigen and the adjuvant are in the bilayer of the polymerized liposome.

22. The polymerized liposome of claim 12 in which the antigen is in the bilayer of the polymerized liposome and the adjuvant is in the interior space of the polymerized lipsome.

3. A method of delivering an antigen to a mammal, said method comprising administering to said mammal a polymerized liposome comprising a phospholipid bilayer having phospholipids that are covalently bonded to each other, an antigen, an adjuvant, and a targeting molecule, wherein the targeting molecule is Ulex Europeans Agglutinin I.

5. The method of claim 3, wherein the liposome is administered orally.

6. The method of claim 3, wherein the administration of the liposome is sublingal, buccal, intranasal, or rectal.

7. The method of claim 3, wherein the liposome is administered through the mucosa.

26. The method of claim 3 in which the antigen and the adjuvant are in the interior space of the polymerized liposome.

28. The method of claim 3 in which the antigen is in the interior space of the polymerized liposome and the adjuvant is in the bilayer of the polymerized liposome.

30. The method of claim 3 in which the antigen and the adjuvant are in the bilayer of the polymerized liposome.

32. The method of claim 3 in which the antigen is in the bilayer of the polymerized liposome and the adjuvant is in the interior space of the polymerized liposome.

4. A method of delivering an antigen to a mammal, said method comprising orally administering to said mammal a polymerized liposome comprising a phospholipid bilayer having phospholipids that are covalently bonded to each other, an antigen, and a targeting molecule, wherein the targeting molecule is a lectin which specifically binds to fucosyl sugars.

8. A polymerized liposome suitable for oral delivery of an antigen to a mammal, said polymerized liposome comprising a phospholipid bilayer having phospholipids that are covalently bonded to each other, an antigen, and a targeting molecule, wherein the targeting molecule is a lectin which specifically binds to 2′

-fucosyllactosamine residues.

9. A polymerized liposome suitable for oral delivery of an antigen to a mammal, said polymerized liposome comprising a phospholipid bilayer having phospholipids that are covalently bonded to each other, an antigen, and a targeting molecule, wherein the targeting molecule is a lectin which specifically binds to M cells with the proviso that the lectin is not WGA.

10. A method of delivering an antigen to a mammal, said method comprising orally administering to said mammal a polymerized liposome comprising a polymerized liposome suitable for oral delivery of an antigen to a mammal, said polymerized liposome comprising a phospholipid bilayer having phospholipids that are covalently bonded to each other, an antigen, and a targeting molecule, wherein the targeting molecule is a lectin which specifically binds to 2′

-fucosyllactosamine residues.

13. The method of claim 4, 10, or 11 wherein the polymerized lipsome further comprises an adjuvant.

27. The method of claim 13 in which the antigen and the adjuvant are in the interior space of the polymerized liposome.

29. The method of claim 13 in which the antigen is in the interior space of the polymerized liposome and the adjuvant is in the bilayer of the polymerized liposome.

31. The method of claim 13 in which the antigen and the adjuvant are in the bilayer of the polymerized liposome.

33. The method of claim 13 in which the antigen is in the bilayer of the polymerized liposome and the adjuvant is in the interior space of the polymerized liposome.

34. The method of claim 3, 4, 10 or 11 in which the antigen is hydrophobic.

35. The method of claim 3, 4, 10 or 11, wherein the antigen is an influenza virus antigen, an HTLV antigen, a rhinovirus antigen, a herpes virus antigen, or Epstein-Barr virus antigen.

36. The method of claim 3, 4, 10 or 11 in which the phospholipid is DODPC.

37. The method of claim 3, 4, 10 or 11 in which the polymerized liposomes have a degree of crosslinking between 30 and 100 percent.

11. A method of delivering an antigen to a mammal, said method comprising orally administering to said mammal a polymerized liposome comprising a polymerized liposome suitable for oral delivery of an antigen to a mammal, said polymerized liposome comprising a phospholipid bilayer having phospholipids that are covalently bonded to each other, an antigen and a targeting molecule, wherein the targeting molecule is a lectin which specifically binds to M cells with the proviso that the lectin is not WGA.