Microparticles with adsorbed polypeptide-containing molecules

1. A microparticle composition comprising: (a) microparticles 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; and (b) a polypeptide-containing molecule adsorbed to the microparticles, wherein the microparticle composition is formed in the absence of surfactant and wherein the microparticles do not contain entrapped or encapsulated polypeptide-containing molecules.

2. The microparticle composition of claim 1 , wherein the polymer comprises a poly(α-hydroxy acid).

3. The microparticle composition of claim 2 , wherein the poly(α-hydroxy acid) is selected from the group consisting of poly(L-lactide), poly(D,L-lactide) and poly(D,L-lactide-co-glycolide).

4. The microparticle composition of claim 3 , wherein the polymer comprises poly(D,L-lactide-co-glycolide).

5. The microparticle composition of claim 4 , wherein the poly(D,L-lactide-co-glycolide) has a lactide/glycolide molar ratio ranging from 25:75 to 75:25 and a molecular weight ranging from 10,000 to 100,000 Daltons.

6. The microparticle composition of claim 4 , wherein the poly(D,L-lactide-co-glycolide) has a lactide/glycolide molar ratio ranging from 40:60 to 60:40 and a molecular weight ranging from 20,000 Daltons to 70,000 Daltons.

7. The microparticle composition of any of claims 1 - 6 , wherein the polypeptide-containing molecule is an antigen.

8. The microparticle composition of claim 7 , wherein the antigen is selected from HIV antigens, meningitis B antigens, streptococcus antigens, hepatitis B virus antigens, hepatitis C virus antigens, Haemophilis influenza type B antigens, pertussis antigens, diphtheria antigens, tetanus antigens, Helicobacter pylori antigens and Influenza A hemagglutinin antigens.

9. The microparticle composition of claim 7 , wherein the antigen is selected from the group consisting of HIV gp41 antigen, HIV gp120 antigen, HIV gp140 antigen, HIV p24gag antigen, HIV p55gag antigen, meningitis B recombinant protein 287 antigen, and group B streptococcus antigen.

10. The microparticle composition of claim 1 , further comprising a pharmaceutically acceptable excipient.

11. The microparticle composition of claim 10 , further comprising an additional biologically active macromolecule selected from the group consisting of a polynucleotide, a polynucleoside, a pharmaceutical, a hormone, an enzyme, a transcription or translation mediator, an intermediate in a metabolic pathway, an immunomodulator, and an adjuvant.

12. The microparticle composition of claim 11 , wherein the additional biologically active macromolecule is an adjuvant.

13. The microparticle composition of claim 12 , wherein the adjuvant is a member selected from the group consisting of CpG oligonucleotides, double-stranded RNA adjuvants, aminoalkyl glucosaminide 4-phosphate adjuvants, imidazoquinoline adjuvants, lipopolysaccharide mimetic adjuvants, saponin adjuvants, E. coli heat-labile toxin adjuvants, monophosphorylipid A adjuvants and aluminum salts.

14. The microparticle composition of claim 12 , wherein the adjuvant is aluminum phosphate.

15. A method of delivering a therapeutically effective amount of a polypeptide-containing molecule to a vertebrate subject, the method comprising the step of administering to the vertebrate subject the microparticle composition of any of claims 10 - 14 .

16. The microparticle composition of claim 7 , wherein the antigen comprises a polysaccharide conjugated to a polypeptide.

17. A method of producing a microparticle composition, the method comprising: (a) forming microparticles by a surfactant-free emulsification process, the microparticles 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; and (b) adsorbing a polypeptide-containing molecule on the surface of the microparticles to form the microparticle composition.

18. The method of claim 17 , wherein the emulsification process comprises: (a) forming an emulsion comprising an organic solvent, water and the polymer; and (b) removing the organic solvent from the emulsion to form microparticles.

19. The method of claim 18 , wherein the emulsion is a water-in-oil-in-water emulsion that is formed by a process comprising: (a) emulsifying an organic phase comprising the polymer and the organic solvent with a first aqueous phase comprising water to form a water-in-oil emulsion; and (b) emulsifying a second aqueous phase comprising water with the emulsion formed in step (a) to form a water-in-oil-in-water emulsion.

20. The method of claim 19 , wherein the emulsifying steps are conducted in a high-shear homogenizer.

21. The method of any of claims 17 - 20 , wherein the polymer is a poly(α-hydroxy acid).

22. The method of any of claims 17 - 20 , wherein the polymer is a poly(D,L-lactide-co-glycolide).

23. The method of claim 22 , wherein the poly(D,L-lactide-co-glycolide) has a lactide/glycolide molar ratio ranging from 25:75 to 75:25 and a molecular weight ranging from 10,000 to 100,000 Daltons.

24. The method of claim 22 , wherein the polymer is a poly(D,L-lactide-co-glycolide) having a lactide/glycolide molar ratio ranging from 40:60 to 60:40 and a molecular weight ranging from 20,000 Daltons to 70,000 Daltons.

25. The method of any of claims 17 - 20 , wherein the polypeptide-containing molecule is an antigen.

26. The method of claim 25 , wherein the antigen is selected from HIV antigens, meningitis B antigens, streptococcus antigens, hepatitis B virus antigens, hepatitis C virus antigens, Haemophilus influenza type B antigens, pertussis antigens, diphtheria antigens, tetanus antigens, Helicobacter pylori antigens and Influenza A hemagglutinin antigens.

27. The method of claim 25 , wherein the antigen is selected from the group consisting of HIV gp41 antigen, HIV gp120 antigen, HIV gp140 antigen, HIV p24gag antigen, HIV p55gag antigen, meningitis B recombinant protein 287 antigen, and group B streptococcus antigen.

28. A microparticle composition formed by a process comprising: (a) forming microparticles by a surfactant-free emulsification process, the microparticles 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; and (b) adsorbing a polypeptide-containing molecule on the surface of the microparticles to form the microparticle composition.

29. The method of any of claims 17 - 20 , wherein a weight-to-weight ratio of the adsorbed polypeptide-containing molecule to the polymer ranges between 0.001:1 and 0.1:1.

30. The microparticle composition of any of claims 1 - 6 , and 10 - 13 , wherein a weight-to-weight ratio of the adsorbed polypeptide-containing molecule to the polymer ranges between 0.01:1 and 0.05:1.

31. The microparticle composition of claim 28 , wherein the polymer comprises a poly(α-hydroxy acid).

32. The microparticle composition of claim 31 , wherein the poly(α-hydroxy acid) is selected from the group consisting of poly(L-lactide), poly(D,L-lactide) and poly(D,L-lactide-co-glycolide).

33. The microparticle composition of claim 28 , wherein the polypeptide-containing molecule is an antigen.

34. The microparticle composition of claim 33 , wherein the antigen is selected from HIV antigens, meningitis B antigens, streptococcus antigens, hepatitis B virus antigens, hepatitis C virus antigens, Haemophilus influenza type B antigens, pertussis antigens, diphtheria antigens, tetanus antigens, Helicobacter pylori antigens and Influenza A hemagglutinin antigens.

35. The microparticle composition of claim 33 , wherein the antigen is selected from the group consisting of HIV gp41 antigen, HIV gp120 antigen, HIV gp140 antigen, HIV p24gag antigen, HIV p55gag antigen, meningitis B recombinant protein 287 antigen, and group B streptococcus antigen.

36. The microparticle composition of claim 28 , further comprising an additional biologically active macromolecule selected from the group consisting of a polynucleotide, a polynucleoside, a pharmaceutical, a hormone, an enzyme, a transcription or translation mediator, an intermediate in a metabolic pathway, an immunomodulator, and an adjuvant.

37. The microparticle composition of claim 36 , wherein the additional biologically active macromolecule is an adjuvant.

38. The microparticle composition of claim 37 , wherein the adjuvant is a member selected from the group consisting of CpG oligonucleotides, double-stranded RNA adjuvants, aminoalkyl glucosaminide 4-phosphate adjuvants, imidazoquinoline adjuvants, lipopolysaccharide mimetic adjuvants, saponin adjuvants, E. coil heat-labile toxin adjuvants, monophosphorylipid A adjuvants and aluminum salts.

39. The microparticle composition of claim 28 , wherein the emulsification process comprises: (a) forming an emulsion comprising an organic solvent, water and the polymer; and (b) removing the organic solvent from the emulsion to form microparticles.

40. The microparticle composition of claim 39 , wherein the emulsion is a water-in-oil-in-water emulsion that is formed by a process comprising: (a) emulsifying an organic phase comprising the polymer and the organic solvent with a first aqueous phase comprising water to form a water-in-oil emulsion; and (b) emulsifying a second aqueous phase comprising water with the emulsion formed in step (a) to form a water-in-oil-in-water emulsion.

41. The microparticle composition of claim 40 , wherein the emulsifying steps are conducted in a homogenizer.