Microparticles with adsorbent surfaces, methods of making same, and uses thereof
Microparticles with adsorbent surfaces, methods of making such microparticles, and uses thereof, are disclosed. The microparticles comprise a polymer, such as a poly(α-hydroxy acid), a polyhydroxy butyric acid, a polycaprolactone, a polyorthoester, a polyanhydride, and the like, and are formed using cationic, anionic, or nonionic detergents. The surface of the microparticles efficiently adsorb biologically active macromolecules, such as DNA, polypeptides, antigens, and adjuvants.
1 . A microparticle comprising: a biodegradable polymer; an anionic detergent; and an antigen comprising a polypeptide 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 , wherein the microparticle comprises 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.
3 . The microparticle of claim 1 , wherein the microparticle comprises a poly(α-hydroxy acid).
4 . The microparticle of claim 1 , wherein the microparticle comprises a poly(α-hydroxy acid) selected from poly(L-lactide), poly(D,L-lactide) and poly(D,L-lactide-co-glycolide).
5 . The microparticle of claim 1 , wherein the microparticle comprises poly(D,L-lactide-co-glycolide).
6 . The microparticle of any of claim 1 , wherein said antigen is derived from a pathogenic organism.
7 . The microparticle of claim 6 , wherein said pathogenic organism is a bacterium.
8 . The microparticle of claim 6 , wherein said pathogenic organism is a virus.
9 . The microparticle of any of claim 3 , wherein said antigen is derived from a pathogenic organism.
10 . The microparticle of claim 9 , wherein said pathogenic organism is a bacterium.
11 . The microparticle of claim 9 , wherein said pathogenic organism is a virus.
12 . The microparticle of any of claim 5 , wherein said antigen is derived from a pathogenic organism.
13 . The microparticle of claim 12 , wherein said pathogenic organism is a bacterium.
14 . The microparticle of claim 12 , wherein said pathogenic organism is a virus.
15 . The microparticle of claim 1 , wherein said antigen is a tumor antigen.
16 . The microparticle of claim 3 , wherein said antigen is a tumor antigen.
17 . The microparticle of claim 5 , wherein said antigen is a tumor antigen.
18 . The microparticle of any claim 1 , wherein the polypeptide is selected from HIV polypeptides, hepatitis B virus polypeptides, hepatitis C virus polypeptides, Haemophilus influenza type B polypeptides, Neisseria meningitides B polypeptides, pertussis polypeptides, diphtheria polypeptides, tetanus polypeptides, and influenza A virus polypeptides.
19 . The microparticle of any claim 3 , wherein the polypeptide is selected from HIV polypeptides, hepatitis B virus polypeptides, hepatitis C virus polypeptides, Haemophilus influenza type B polypeptides, Neisseria meningitides B polypeptides, pertussis polypeptides, diphtheria polypeptides, tetanus polypeptides, and influenza A virus polypeptides.
20 . The microparticle of claim 5 , wherein the polypeptide is selected from HIV polypeptides, hepatitis B virus polypeptides, hepatitis C virus polypeptides, Haemophilus influenza type B polypeptides, Neisseria meningitides B polypeptides, pertussis polypeptides, diphtheria polypeptides, tetanus polypeptides, and influenza A virus polypeptides.
21 . The microparticle of claim 1 , wherein the antigen is selected from an HIV gp120 antigen, an HIV gp160 antigen, an HIV p24gag antigen, an HIV p55gag antigen, and an Influenza A hemagglutinin antigen.
22 . The microparticle of claim 3 , wherein the antigen is selected from an HIV gp120 antigen, an HIV gp160 antigen, an HIV p24gag antigen, an HIV p55gag antigen, and an Influenza A hemagglutinin antigen.
23 . The microparticle of claim 5 , wherein the antigen is selected from an HUV gp120 antigen, an HIV gp160 antigen, an HIV p24gag antigen, an HIV p55gag antigen, and an Influenza A hemagglutinin antigen.
24 . The microparticle of claim 1 , wherein the anionic detergent is sodium dodecyl sulfate.
25 . The microparticle of claim 1 , wherein said microparticle does not comprise an entrapped antigen.
26 . The microparticle of claim 1 , wherein said microparticle is formed in a double emulsion process.
27 . The microparticle of claim 1 , wherein the microparticle has a diameter between 500 nanometers and 10 microns.
28 . The microparticle of claim 3 , wherein the microparticle has a diameter between 500 nanometers and 10 microns.
29 . The microparticle of claim 5 , wherein the microparticle has a diameter between 500 nanometers and 10 microns.
30 . 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.
31 . The microparticle of claim 3 , 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.
32 . The microparticle of claim 5 , 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.
33 . A microparticle composition comprising a microparticle according to claim 1 and a pharmaceutically acceptable excipient.
34 . A microparticle composition comprising a microparticle according to claim 1 , a pharmaceutically acceptable excipient, and an immunological adjuvant.
35 . The microparticle composition of claim 34 , 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.
36 . The microparticle composition of claim 33 , wherein said microparticle composition is an injectable composition.
37 . The microparticle composition of claim 34 , wherein said microparticle composition is an injectable composition.
38 . A method of raising an immune response, comprising: providing the microparticle composition of claim 33 , and administering said microparticle composition to a vertebrate animal.
39 . A method of raising an immune response, comprising: providing the microparticle composition of claim 34 , and administering said microparticle composition to a vertebrate animal.
40 . The microparticle of claim 1 , comprising an immunological adjuvant adsorbed to said microparticle.
41 . The microparticle of claim 3 , comprising an immunological adjuvant adsorbed to said microparticle.
42 . The microparticle of claim 5 , comprising an immunological adjuvant adsorbed to said microparticle.
43 . A method of claim 38 further comprising separately administering an immunological adjuvant in a separate composition.
44 . The composition of claim 33 , comprising a plurality of antigens.