US2005208143A1PendingUtilityA1

Microparticles with adsorbent surfaces, methods of making same, and uses thereof

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Assignee: O' HAGAN DEREKPriority: Jan 30, 1997Filed: Apr 25, 2005Published: Sep 22, 2005
Est. expiryJan 30, 2017(expired)· nominal 20-yr term from priority
Inventors:Derek O' HaganManmohan SinghGary S. OttJohn BarackmanJina Kazzaz
A61K 2039/543C12N 2740/16111A61K 39/39A61K 9/167A61K 2039/55505C12N 2740/16234A61K 39/21C12N 2740/16134A61K 2039/53A61K 39/12A61K 2039/55561A61K 2039/545C12N 2770/24234A61K 9/1647A61K 39/245C12N 2770/24211A61K 2039/55555
61
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Claims

Abstract

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.

Claims

exact text as granted — not AI-modified
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.

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