Targeted polymerized liposomes for improved drug delivery

• US 6,004,534 A
• Filed: 04/18/1997
• Issued: 12/21/1999
• Est. Priority Date: 07/23/1993
• 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): Lovering, Richard D.
• Application Number:
  US08/844,137
• Time in Patent Office: 977 Days
• Field of Search: 424/450, 424/1.21, 424/9.321, 424/9.51, 424/184.1, 424/812, 424/9.4, 428/402.2, 264/4.1, 264/4.3
• US Class Current: 424/9.321
• 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 424/812 Liposome comprising an antibody, antibody fragment, antigen, or other specific or nonspecific immunoeffector
• 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 in order to optimize the immune response to the encapsulated antigen or the efficacy of the encapsulated drug.

Claims

1. A polymerized liposome suitable for oral delivery of a biologically active substance comprising a phospholipid bilayer having covalently bound phospholipids, an aqueous core and a bioactive molecule, wherein said liposome is modified to contain a targeting molecule which is selected from the group consisting of glycoproteins, lectins, carbohydrates, bacterial proteins and viral proteins.

2. The polymerized liposomes of claim 1 further comprising a vaccine, an antigen, biologically active drugs and detectable molecules.

3. The polymerized liposome of claim 1 wherein the targeting molecule is a lectin.

4. The liposomes of claim 1 wherein the biologically active substances are selected from the group consisting of cells, viruses, vectors, proteins, peptides nucleic acids, polysaccharides and carbohydrates, lipids, glycoproteins, and combinations thereof, and synthetic organic and inorganic drugs exerting a biological effect when administered to an animal.

5. The polymerized liposomes of claim 4 wherein the biologically active substance is an antigen.

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

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

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

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

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

12. A pharmaceutical composition suitable for oral delivery which comprises a polymerized liposome of claim 1 and a pharmaceutically acceptable excipient or carrier suitable for oral delivery.

13. The polymerized liposome of claim 1 wherein the targeting molecule is covalently bonded to said polymerized liposome.

14. A method of orally delivering molecules to an animal which comprises administering to said animal polymerized liposomes comprising a phospholipid bilayer having covalently bonded phospholipids, an aqueous core, a targeting molecule selected from the group consisting of glycolproteins, lectins, carbohydrates, bacterial proteins and viral proteins and a bioactive molecule.

15. The method of claim 14 wherein the biologically active substance is a detectable compound selected from the group consisting of radiopaque substances, air, magnetic materials, and substances detectable by magnetic resonance imaging.

16. 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, and combinations thereof, and synthetic organic and inorganic drugs exerting a biological effect when administered to an animal.

17. 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.

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