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;
a detergent selected from a cationic detergent and an anionic detergent; and
an immunological adjuvant, wherein said immunological adjuvant is adsorbed on the surface of said microparticle.
2 . The microparticle of claim 1 , further comprising an antigen derived from a pathogenic organism or a tumor, wherein said antigen is adsorbed on the surface of said microparticle, encapsulated within said microparticle, or both.
3 . The microparticle of claim 1 , wherein the biodegradable polymer is selected from the group consisting of a poly(a-hydroxy acid), a polyhydroxy butyric acid, a polycaprolactone, a polyorthoester, a polyanhydride, and a polycyanoacrylate.
4 . The microparticle of claim 1 , wherein the microparticle comprises a poly(a-hydroxy acid) selected from the group consisting of poly(L-lactide), poly(D,L-lactide) and poly(D,L-lactide-co-glycolide).
5 . The microparticle of claim 1 , wherein the microparticle comprises a cationic detergent.
6 . The microparticle of claim 1 , wherein the microparticle comprises an anionic detergent.
7 . The microparticle of claim 2 , wherein the antigen is an antigen comprising a polypeptide.
8 . The microparticle of claim 2 , wherein the antigen is an antigen comprising a polynucleotide.
9 . The microparticle of claim 1 , wherein the microparticle further comprises an immunological adjuvant encapsulated within the microparticle.
10 . The microparticle of claim 1 , wherein the immunological adjuvant is selected from a CpG oligonucleotide, an E. coli heat-labile toxin, a monophosphorylipid A compound, and an aluminum salt.
11 . The microparticle of claim 2 , wherein the microparticle comprises a cationic detergent.
12 . The microparticle of claim 2 , wherein the microparticle comprises an anionic detergent.
13 . A method of producing a microparticle, said method comprising the steps of:
(a) providing an emulsion comprising (i) an organic solvent, (ii) a biodegradable polymer, (iii) water and (iv) a detergent selected from a cationic detergent and an anionic detergent, wherein the detergent is present in the mixture at a weight to weight detergent to polymer ratio of from about 0.00001:1 to about 0.1:1;
(b) removing the organic solvent from the emulsion; and
(c) adsorbing an immunological adjuvant on the surface of said microparticle.
14 . The method of claim 13 , wherein the detergent comprises an anionic detergent.
15 . The method of claim 13 , wherein the detergent comprises a cationic detergent.
16 . The method of claim 13 , wherein the detergent further comprises a nonionic detergent.
17 . The method of claim 13 , wherein the detergent is present at a weight to weight detergent to polymer ratio of from about 0.0001:1 to about 0.1:1.
18 . The method of claim 13 , wherein the detergent is present at a weight to weight detergent to polymer ratio of from about 0.001:1 to about 0.1:1.
19 . The method of claim 13 , wherein the biodegradable polymer comprises a poly(a-hydroxy acid), a polyhydroxy butyric acid, a polycaprolactone, a polyorthoester, a polyanhydride, or a polycyanoacrylate.
20 . The method of claim 13 , wherein the biodegradable polymer comprises a poly(a-hydroxy acid) selected from the group consisting of poly(L-lactide), poly(D,L-lactide) and poly(D,L-lactide-co-glycolide).
21 . The method of claim 13 , wherein the biodegradable polymer comprises poly(lactide-co-glycolide).
22 . The method of claim 13 , wherein the polymer is present at a concentration of about 1% to about 30% relative to the organic solvent.
23 . The method of claim 13 , wherein the biodegradable polymer comprises poly(D,L-lactide-co-glycolide) and is present at a concentration of about 3% to about 10% relative to the organic solvent.
24 . The method of claim 13 , wherein said emulsion is a water-in-oil-in-water emulsion.
25 . The method of claim 13 , further comprising providing an antigen derived from a pathogenic organism or a tumor, wherein said antigen is adsorbed on the surface of said microparticle, encapsulated within said microparticle, or both.
26 . The method of claim 25 , wherein the antigen is adsorbed on the surface of said microparticle.
27 . The method of claim 25 , wherein the antigen is an antigen comprising a polynucleotide.
28 . The method of claim 25 , wherein the antigen is an antigen comprising a polypeptide.
29 . The method of claim 13 , further comprising providing an immunological adjuvant within the microparticle.
30 . A microparticle made according to the method of claim 13 .
31 . A microparticle composition comprising a microparticle produced by the method of claim 30 and a pharmaceutically acceptable excipient.
32 . A method of delivering a therapeutically effective amount of an immunological adjuvant to a vertebrate subject comprising the step of administering to the vertebrate subject a microparticle composition of claim 31 .
33 . Use of a microparticle composition of claim 31 for treatment of a disease.
34 . Use of a microparticle composition of claim 31 for a vaccine.
35 . Use of a microparticle composition of claim 31 for raising an immune response.
36 . The microparticle of claim 5 , wherein said immunological adjuvant comprises an immunostimulating nucleotide sequence.
37 . The microparticle of claim 36 , wherein the immunological adjuvant comprises a CpG oligonucleotide.
38 . The microparticle of claim 11 , wherein the antigen (a) is adsorbed on the surface of the microparticle and (b) comprises a polynucleotide.
39 . The microparticle of claim 12 , wherein the antigen (a) is adsorbed on the surface of the microparticle and (b) comprises a polypeptide.
40 . The microparticle of claim 2 , wherein said antigen is selected from HIV antigens, hepatitis B virus antigens, hepatitis C virus antigens, Haemophilus influenza type B antigens, meningitis B antigens, pertussis antigens, diphtheria antigens, tetanus antigens and influenza A virus antigens.
41 . The microparticle of claim 2 , wherein the antigen comprises a plasmid DNA molecule.
42 . The microparticle of claim 1 , wherein the microparticle has a diameter between 500 nanometers and 30 microns.
43 . The microparticle of claim 1 , wherein the microparticle comprises poly(lactide-co-glycolide).
44 . The microparticle of claim 3 , wherein the microparticle comprises an anionic detergent.
45 . The microparticle of claim 3 , wherein the microparticle comprises a cationic detergent.
46 . A microparticle composition comprising a microparticle of claim 1 , and a pharmaceutically acceptable excipient.
47 . The microparticle composition claim 46 , wherein said microparticle composition is an injectable composition.
48 . A method of delivering a therapeutically effective amount of an immunological adjuvant to a vertebrate subject comprising the step of administering to the vertebrate subject a microparticle composition of claim 46 .
49 . Use of a microparticle composition of claim 46 for treatment of a disease.
50 . Use of a microparticle composition of claim 46 for a vaccine.
51 . Use of a microparticle composition of claim 46 for raising an immune response.
52 . A microparticle composition comprising a microparticle of claim 42 and a pharmaceutically acceptable excipient.
53 . The microparticle composition claim 52 , wherein said microparticle composition is an injectable composition.
54 . A method of delivering a therapeutically effective amount of an immunological adjuvant to a vertebrate subject comprising the step of administering to the vertebrate subject a microparticle composition of claim 52 .
55 . Use of a microparticle composition of claim 52 for treatment of a disease.
56 . Use of a microparticle composition of claim 52 for a vaccine.
57 . Use of a microparticle composition of claim 52 for raising an immune response.
58 . A microparticle composition comprising a microparticle of claim 43 and a pharmaceutically acceptable excipient.
59 . The microparticle composition claim 58 , wherein said microparticle composition is an injectable composition.
60 . A method of delivering a therapeutically effective amount of an immunological adjuvant to a vertebrate subject comprising the step of administering to the vertebrate subject a microparticle composition of claim 58 .
61 . Use of a microparticle composition of claim 58 for treatment of a disease.
62 . Use of a microparticle composition of claim 58 for a vaccine.
63 . Use of a microparticle composition of claim 58 for raising an immune response.
64 . A microparticle composition comprising a microparticle of claim 44 and a pharmaceutically acceptable excipient.
65 . The microparticle composition claim 64 , wherein said microparticle composition is an injectable composition.
66 . A method of delivering a therapeutically effective amount of an immunological adjuvant to a vertebrate subject comprising the step of administering to the vertebrate subject a microparticle composition of claim 64 .
67 . Use of a microparticle composition of claim 64 for treatment of a disease.
68 . Use of a microparticle composition of claim 64 for a vaccine.
69 . Use of a microparticle composition of claim 64 for raising an immune response.
70 . A microparticle composition comprising a microparticle of claim 45 and a pharmaceutically acceptable excipient.
71 . The microparticle composition claim 70 , wherein said microparticle composition is an injectable composition.
72 . A method of delivering a therapeutically effective amount of an immunological adjuvant to a vertebrate subject comprising the step of administering to the vertebrate subject a microparticle composition of claim 70 .
73 . Use of a microparticle composition of claim 70 for treatment of a disease.
74 . Use of a microparticle composition of claim 70 for a vaccine.
75 . Use of a microparticle composition of claim 70 for raising an immune response.