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

• US 6,060,082 A
• Filed: 04/18/1997
• Issued: 05/09/2000
• Est. Priority Date: 04/18/1997
• Status: Expired due to Fees

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Langer, Robert S., Chen, Hongming
• Primary Examiner(s): Kishore, Gollamudi S.
• Application Number:
  US08/844,138
• Time in Patent Office: 1,117 Days
• Field of Search: 424/450, 424/1.21, 424/9.321, 424/9.51, 424/417, 436/829, 935/54
• 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. Polymerized liposomes comprising a phospholipid bilayer having covalently bonded phospholipids, an aqueous core and a lectin wherein the lectin is Ulex Europeans Agglutinin I.

2. The liposomes of claim 1 further comprising an antigen, a biologically active molecule or a detectable molecule.

3. The liposome of claim 1 wherein the targeting molecule is modified Ulex Europaeus Agglutinin.

4. The liposomes of claim 2 wherein the biologically active molecule is selected from the group consisting of cells, viruses, vectors, proteins, peptides, nucleic acids, polysaccharides, carbohydrates, lipids, glycoproteins, drugs or combinations thereof.

5. The liposomes of claim 2 wherein the biologically active molecule is an antigen.

6. The liposomes of claim 5 wherein the antigen is influenza hemeagglutinin.

7. The liposomes of claim 5 wherein the antigen is the ospA antigen from Lyme disease bacteria.

8. The liposomes of claim 5 wherein the antigen is a fragment of diphtheria toxin.

9. The liposomes of claim 1 having a degree of crosslinking between 30 and 100 percent.

10. The liposomes of claim 1 comprising phospholipids selected from the group consisting of double bond-containing olefinic and acetylenic phospholipids and phospholipids containing thiol groups.

11. The liposomes of claim 1 having a diameter of between fifteen nm and ten microns.

12. The polymerized liposome of claim 1 wherein said phospholipid is DODPC.

13. The polymerized liposome of claim 12 wherein the polymerized liposome comprises about 85 to 100% DODPC.

14. A method of delivering therapeutic molecules to an animal which comprises administering to said animal polymerized liposomes comprising a phospholipid bilayer having covalently bonded phospholipids;

an aqueous core;

a lectin wherein the lectin is Ulex Europeans Agglutinin(UEA) therapeutic molecule.

15. The method of claim 14 further comprising at least one targeting molecule selected from the group consisting of glycoproteins, antibodies, antibody fragments, or cell surface receptors and ligands.

16. The method of claim 14 wherein the therapeutic molecule is a detectable compound selected from the group consisting of radiopaque substances, air, magnetic materials, or substances detectable by magnetic resonance imaging.

17. The method of claim 14 wherein the molecules are biologically active substances selected from the group consisting of cells, viruses, vectors, proteins, peptides, nucleic acids, polysaccharides and carbohydrates, lipids, glycoproteins, or combinations thereof, and synthetic organic and inorganic drugs exerting a biological effect when administered to an animal.

18. The method of claim 14 wherein the biologically active substance is an antigen and the liposomes are administered to the animal in an amount effective to elicit a humoral or cell mediated immune response against the antigen.

19. The method of claim 14 further comprising providing an adjuvant in the hydrophobic layer of the liposome.

20. The method of claim 14 wherein the administration is by an oral route.

21. The method of claim 14 wherein the administration of sublingual, buccal, or rectal.

22. The method of claim 14 wherein the administration is through mucosa.

23. A method of orally delivering therapeutics to a mammal which comprises administering to said mammal a polymerized liposome comprising a polymerized phospholipid bilayer, therapeutic agent encapsulated in an aqueous core of said liposome and a lectin wherein the lectin is Ulex Europeans Agglutinin(UEA).