Microparticles with adsorbent surfaces, methods of making same, and uses thereof
The present invention is directed to microparticles, to microparticle compositions containing the same, to methods of forming the same, and to uses for the same, including use for a vaccine, for raising an immune response, for treatment of a disease and for diagnosis of a disease. The microparticles comprise a biodegradable polymer, such as a poly(α-hydroxy acid), a polyhydroxy butyric acid, a polycaprolactone, a polyorthoester, a polyanhydride, or a polycyanoacrylate, and a detergent selected from a cationic detergent and an anionic detergent. The microparticles further comprise an antigen adsorbed on the surface of the microparticle.
1. A microparticle comprising: a polymer selected from the group consisting of a poly(α-hydroxy acid), a polyhydroxy butyric acid, a polycaprolactone, a polyorthoester, a polyanhydride, and a polycyanoacrylate; a cationic detergent; and an antigen comprising a polynucleotide adsorbed on the surface of said microparticle,
wherein said microparticle is formed by a process that comprises: forming a microparticle comprising said polymer and said detergent, said microparticle being formed in the presence of said detergent; and exposing said microparticle to said antigen.
2. The microparticle of claim 1 , further comprising an additional biologically active macromolecule encapsulated within said microparticle, wherein the additional biologically active macromolecule is selected from a polypeptide, a polynucleotide, a polynucleoside, an antigen, a hormone, an enzyme, and an immunological adjuvant.
3. The microparticle of claim 2 , wherein the additional biologically active macromolecule is an immunological adjuvant.
4. The microparticle of claim 3 , wherein the immunological adjuvant is an aluminum salt.
5. The microparticle of claim 1 , wherein the poly(α-hydroxy acid) is selected from poly(L-lactide), poly(D,L-lactide) and poly(D,L-lactide-co-glycolide).
6. The microparticle of claim 1 , wherein the polymer is poly(D,L-lactide-co-glycolide).
7. The microparticle of claim 1 , wherein said polynucleotide encodes a polypeptide selected from an HIV gp 160polypeptide, an HIV p24gag polypeptide, an HIV p55gag polypeptide, and an Influenza A hemagglutinin polypeptide.
8. The microparticle of claim 1 , wherein said polynucleotide encodes an HIV gp 120 polypeptide.
9. The microparticle of claim 1 wherein the cationic detergent is hexadecyltrimethylammonium bromide.
10. A microparticle composition comprising a microparticle of any one of claims 1 , 2 - 6 and 7 - 4 and a pharmaceutically acceptable excipient.
11. The microparticle composition of claim 10 , wherein said microparticle composition is an injectable composition.
12. A microparticle composition comprising a microparticle according to any one of claims 1 , 5 , 6 , 7 and 8 , a pharmaceutically acceptable excipient, and an immunological adjuvant.
13. A microparticle composition of claim 12 , wherein the immunological adjuvant is selected from CpG oligonucleotides, E. coli heat-labile toxin-K63 (LTK63), E. coli heat-labile toxin-R72 (LTR72) monophosphorylipid A (MPL), and an aluminum salt.
14. A microparticle composition of claim 13 , wherein the aluminum salt is aluminum phosphate.
15. The microparticle composition of claim 12 , wherein said microparticle composition is an injectable composition.
16. The microparticle of any one of claims 1 , 2 - 6 and 7 - 4 , wherein said polynucleotide is a plasmid DNA molecule.
17. A microparticle composition comprising a microparticle of claim 16 and a pharmaceutically acceptable excipient.
18. The microparticle composition of claim 17 , wherein said microparticle composition is an injectable composition.
19. The microparticle of any of claims 1 , 2 - 6 , 3 and 4 , wherein the polynucleotide encodes a polypeptide selected from HIV polypeptides, hepatitis B virus polypeptides, hepatitis C virus polypeptides, Haemophilus influenza type B polypeptides, pertussis polypeptides, diphtheria polypeptides, tetanus polypeptides, and influenza A virus polypeptides.
20. A microparticle composition comprising a microparticle of claim 19 and a pharmaceutically acceptable excipient.
21. The microparticle composition of claim 20 , wherein said microparticle composition is an injectable composition.
22. The microparticle of any one of claims 1 , 2 - 6 , 7 - 4 and 9 , wherein said microparticle does not comprise an entrapped antigen.
23. The microparticle of any one of claims 1 , 2 - 6 , 7 - 4 and 9 , wherein said microparticle is formed in a double emulsion process.
24. The microparticle of any one of claims 1 , 2 - 6 , 3 , 4 and 9 , wherein the polynucleotide encodes a polypeptide derived from a pathogenic organism.
25. The microparticle of claim 24 wherein said pathogenic organism is a bacterium.
26. The microparticle of claim 24 , wherein said pathogenic organism is a virus.
27. A microparticle composition comprising a microparticle of claim 24 and a pharmaceutically acceptable excipient.
28. The microparticle composition of claim 27 , wherein said microparticle composition is an injectable composition.
29. The microparticle of any one of claims 1 , 2 - 6 , 7 - 4 and 9 , wherein the microparticle has a diameter between 500 nanometers and 10 microns.
30. A microparticle composition comprising a microparticle of claim 29 and a pharmaceutically acceptable excipient.
31. The microparticle composition of claim 30 , wherein said microparticle composition is an injectable composition.
32. The microparticle of any one of claims 1 , 2 , 5 , 6 , 3 and 4 , wherein said polynucleotide encodes a polypeptide derived from a tumor antigen.
33. A microparticle composition comprising a microparticle of claim 32 and a pharmaceutically acceptable excipient.
34. The microparticle composition of claim 32 wherein said microparticle composition is an injectable composition.
35. The microparticle of any one of claims 2 , 7 - 4 and 9 , wherein the polymer is poly(D,L-lactide-co-glycolide).
36. A microparticle composition comprising a microparticle of claim 35 and a pharmaceutically acceptable excipient.
37. The microparticle composition of claim 36 , wherein said microparticle composition is an injectable composition.
38. A method of raising an immune response, comprising:
providing the microparticle composition of claim 10 , and administering said microparticle composition to a vertebrate animal.
39. A method of raising an immune response, comprising: providing the microparticle composition of claim 12 , and administering said microparticle composition to a vertebrate animal.
40. A method of raising an immune response, comprising:
providing the microparticle composition of claim 17 , and administering said microparticle composition to a vertebrate animal.
41. A method of raising an immune response, comprising:
providing the microparticle composition of claim 30 , and administering said microparticle composition to a vertebrate animal.
42. A method of raising an immune response, comprising:
providing the microparticle composition of claim 36 , and administering said microparticle composition to a vertebrate animal.
43. A method of raising an immune response, comprising:
providing the microparticle composition of claim 20 , and administering said microparticle composition to a vertebrate animal.
44. A method of raising an immune response, comprising:
providing the microparticle composition of claim 27 , and administering said microparticle composition to a vertebrate animal.
45. A method of raising an immune response, comprising:
providing the microparticle composition of claim 33 , and administering said microparticle composition to a vertebrate animal.
46. A microparticle comprising: a biodegradable polymer; a cationic detergent; and an antigen comprising a polynucleotide adsorbed on the surface of said microparticle,
wherein said microparticle is formed by a process that comprises: forming a microparticle comprising said polymer and said detergent, said microparticle being formed in the presence of said detergent; and exposing said microparticle to said antigen.
47. The microparticle of claim 46 , further comprising an additional biologically active macromolecule encapsulated within said microparticle, wherein the additional biologically active macromolecule is selected from a polypeptide, a polynucleotide, a polynucleoside, an antigen, a hormone, an enzyme, and an immunological adjuvant.
48. A microparticle composition comprising a microparticle of any one of claims 46 and 47 and a pharmaceutically acceptable excipient.
49. The microparticle composition of claim 48 , wherein said microparticle composition is an injectable composition.
50. A microparticle composition comprising a microparticle according to any one of claims 46 and 47 a pharmaceutically acceptable excipient, and an immunological adjuvant.
51. The microparticle of composition of claim 50 , wherein said microparticle composition is an injectable composition.
52. A method of raising an immune response, comprising:
providing the microparticle composition of claim 48 , and administering said microparticle composition to a vertebrate animal.
53. A method of raising an immune response, comprising:
providing the microparticle composition of claim 50 , and administering said microparticle composition to a vertebrate animal.