Apparatus and method for transdermal delivery of multiple vaccines

• US 20050271684A1
• Filed: 03/18/2005
• Published: 12/08/2005
• Est. Priority Date: 04/13/2004
• Status: Abandoned Application

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Daddona, Peter E., Trautman, Joseph C., Cormier, Michel J.N.
• Application Number:
  US11/084,635
• Publication Number:
  US 20050271684A1
• Time in Patent Office: Days
• US Class Current: 424/204.100
• CPC Class Codes: A61K 2039/525 Virus
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0046 Solid microneedles
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 37/0015 by using microneedles

Abstract

An apparatus and method for transdermally delivering an immunologically active agent comprising a delivery system having a microprojection array that includes a plurality of microprojections that are adapted to pierce through the stratum corneum into the underlying epidermis layer, or epidermis and dermis layers, the microprojection array having a plurality of array regions, each of the array regions having a different biocompatible coating disposed thereon, wherein at least one of the array region coatings includes an immunologically active agent. In one embodiment, each coating on the array regions includes a different immunologically active agent. In another embodiment, the biocompatible coating on a first array region includes an immunologically active agent and the biocompatible coating on a second array region includes an immune response augmenting adjuvant.

Claims

1. A system for transdermally delivering multiple immunologically active agents, comprising a microprojection array having a plurality of stratum corneum-piercing microprojections, said microprojection array having at least first and second array regions, said first array region having a first biocompatible coating disposed thereon, said second array region having a second biocompatible coating disposed thereon, wherein said first biocompatible coating includes at least one immunologically active agent.

2. The system of claim 1, wherein said second biocompatible coating includes an immune response augmenting adjuvant.

3. The system of claim 1, wherein said immunologically active agent is selected from the group consisting of viruses, bacteria, protein-based vaccines, polysaccharide-based vaccine, and nucleic acid-based vaccines.

4. The system of claim 1, wherein said immunologically active agent is selected from the group consisting of viruses, weakened viruses, killed viruses, bacteria, weakened bacteria, killed bacteria, protein-based vaccines, polysaccharide-based vaccine, nucleic acid-based vaccines, proteins, polysaccharide conjugates, oligosaccharides, lipoproteins, Bordetella pertussis (recombinant PT vaccine—

acellular), Clostridium tetani (purified, recombinant), Corynebacterium diphtheriae (purified, recombinant), Cytomegalovirus (glycoprotein subunit), Group A streptococcus (glycoprotein subunit, glycoconjugate Group A polysaccharide with tetanus toxoid, M protein/peptides linked to toxing subunit carriers, M protein, multivalent type-specific epitopes, cysteine protease, C5a peptidase), Hepatitis B virus (recombinant Pre S1, Pre-S2, S, recombinant core protein), Hepatitis C virus (recombinant—

expressed surface proteins and epitopes), Human papillomavirus (Capsid protein, TA-GN recombinant protein L2 and E7[from HPV-6], MEDI-501 recombinant VLP L1 from HPV-11, Quadrivalent recombinant BLP L1 [from HPV-6], HPV-11, HPV-16, and HPV-18, LAMP-E7[from HPV-16]), Legionella pneumophila (purified bacterial survace protein), Neisseria meningitides (glycoconjugate with tetanus toxoid), Pseudomonas aeruginosa (synthetic peptides), Rubella virus (synthetic peptide), Streptococcus pneumoniae (glycoconjugate [1, 4, 5, 6B, 9N, 14, 18C, 19V, 23F] conjugated to meningococcal B OMP, glycoconjugate [4, 6B, 9V, 14, 18C, 19F, 23F] conjugated to CRM197, glycoconjugate [1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F] conjugated to CRM1970, Treponema pallidum (surface lipoproteins), Varicella zoster virus (subunit, glycoproteins), Vibrio cholerae (conjugate lipopolysaccharide), cytomegalo virus, hepatitis B virus, hepatitis C virus, human papillomavirus, rubella virus, varicella zoster, bordetella pertussis, clostridium tetani, corynebacterium diphtheriae, group A streptococcus, legionella pneumophila, neisseria meningitdis, pseudomonas aeruginosa, streptococcus pneumoniae, treponema pallidum, vibrio cholerae, flu vaccines, Lyme disease vaccines, rabies vaccines, measles vaccines, mumps vaccines, chicken pox vaccines, small pox vaccines, hepatitis vaccines, pertussis vaccines, diphtheria vaccines, nucleic acids, single-stranded nucleic acids, double-stranded nucleic acids, supercoiled plasmid DNA, linear plasmid DNA, cosmids, bacterial artificial chromosomes (BACs), yeast artificial chromosomes (YACs), mammalian artificial chromosomes, RNA molecules, and mRNA.

5. The system of claim 1, wherein said immunologically active agent includes an immune response augmenting adjuvant selected from the group consisting of aluminum phosphate gel, aluminum hydroxide, alpha glucan, β

-glucan, cholera toxin B subunit, CRL1005, ABA block polymer with mean values of x=8 and y=205, gamma inulin, linear (unbranched) β

-D(2->

1) polyfructofuranoxyl-α

-D-glucose, Gerbu adjuvan, N-acetylglucosamine-(β

1-4)-N-acetylmuramyl-L-alanyl-D-glutamine (GMDP), dimethyl dioctadecylammonium chloride (DDA), zinc L-proline salt complex (Zn-Pro-8), Imiquimod (1-(2-methypropyl)-1H-imidazo[4,5-c]quinolin-4-amine, ImmTher™

, N-acetylglucoaminyl-N-acetylmuramyl-L-Ala-D-isoGlu-L-Ala-glycerol dipalmitate, MTP-PE liposomes, C₅₉H₁₀₈N₆O₁₉PNa-3H₂O (MTP), Murametide, Nac-Mur-L-Ala-D-Gln-OCH₃, Pleuran, QS-21;

S-28463, 4-amino-a, a-dimethyl-1H-imidazo[4,5-c]quinoline-1-ethanol, sclavo peptide, VQGEESNDK.HCl (IL-1β

163-171 peptide), threonyl-MDP (Termurtide™

), N-acetyl muramyl-L-threonyl-D-isoglutamine, interleukine 18 (IL-18), IL-2 IL-12, IL-15, IL-4, IL-10, DNA oligonucleotides, CpG containing oligonucleotides, gamma interferon, and NF kappa B regulatory signaling proteins.

6. The system of claim 2, wherein said immune response augmenting adjuvant is selected from the group consisting of aluminum phosphate gel, aluminum hydroxide, alpha glucan, β

-glucan, cholera toxin B subunit, CRL1005, ABA block polymer with mean values of x=8 and y=205, gamma inulin, linear (unbranched) β

-D(2->

1) polyfructofuranoxyl-α

-D-glucose, Gerbu adjuvan, N-acetylglucosamine-(β

1-4)-N-acetylmuramyl-L-alanyl-D-glutamine (GMDP), dimethyl dioctadecylammonium chloride (DDA), zinc L-proline salt complex (Zn-Pro-8), Imiquimod (1-(2-methypropyl)-1H-imidazo[4,5-c]quinolin-4-amine, ImmTher™

, N-acetylglucoaminyl-N-acetylmuramyl-L-Ala-D-isoGlu-L-Ala-glycerol dipalmitate, MTP-PE liposomes, C₅₉H₁₀₈N₆O₁₉PNa-3H₂O (MTP), Murametide, Nac-Mur-L-Ala-D-Gln-OCH₃, Pleuran, QS-21;

S-28463, 4-amino-a, a-dimethyl-1H-imidazo[4,5-c]quinoline-1-ethanol, sclavo peptide, VQGEESNDK.HCl (IL-1β

163-171 peptide), threonyl-MDP (Termurtide™

M), N-acetyl muramyl-L-threonyl-D-isoglutamine, interleukine 18 0(IL-18), IL-2 IL-12, IL-15, IL4, IL-10, DNA oligonucleotides, CpG containing oligonucleotides, gamma interferon, and NF kappa B regulatory signaling proteins.

7. The system of claim 1, wherein said microprojection member has a microprojection density of at least approximately 100 microprojections/cm².

8. The system of claim 7, wherein said microprojection member has a microprojection density in the range of approximately 200-3000 microprojections/cm².

9. The system of claim 1, wherein each of said microprojections has a length less than 1000 microns.

10. The system of claim 9, wherein each of said microprojections has a length in the range of approximately 50-145 microns.

11. The system of claim 1, wherein said first and second biocompatible coatings have a thickness in the range of approximately 2-50 microns.

12. The system of claim 1, wherein said first and second biocompatible coatings are formed from a coating formulation.

13. The system of claim 12, wherein said coating formulation comprises an aqueous formulation.

14. The system of claim 12, wherein said coating formulation includes a surfactant.

15. The system of claim 14, wherein said surfactant is selected from the group consisting of sodium lauroamphoacetate, sodium dodecyl sulfate (SDS), cetylpyridinium chloride (CPC), dodecyltrimethyl ammonium chloride (TMAC), benzalkonium, chloride, polysorbates, such as Tween 20 and Tween 80, sorbitan derivatives, sorbitan laurate, alkoxylated alcohols, and laureth-4.

16. The system of claim 12, wherein said coating formulation includes an amphiphilic polymer.

17. The system of claim 16, wherein said amphiphilic polymer is selected from the group consisting of cellulose derivatives, hydroxyethylcellulose (HEC), hydroxypropyl-methylcellulose (HPMC), hydroxypropycellulose (HPC), methylcellulose (MC), hydroxyethylmethylcellulose (HEMC), ethylhydroxyethylcellulose (EHEC), and pluronics.

18. The system of claim 12, wherein said coating formulation includes a hydrophilic polymer.

19. The system of claim 18, wherein said hydrophilic polymer is selected from the group consisting of poly(vinyl alcohol), poly(ethylene oxide), poly(2-hydroxyethylmethacrylate), poly(n-vinyl pyrolidone), polyethylene glycol and mixtures thereof.

20. The system of claim 12, wherein said coating formulation includes a biocompatible carrier.

21. The system of claim 20, wherein said biocompatible polymer is selected from the group consisting of human albumin, bioengineered human albumin, polyglutamic acid, polyaspartic acid, polyhistidine, pentosan polysulfate, polyamino acids, sucrose, trehalose, melezitose, raffinose and stachyose.

22. The system of claim 12, wherein said coating formulation includes a stabilizing agent selected from the group consisting of a non-reducing sugar, a polysaccharide, a reducing sugar, and a DNase inhibitor.

23. The system of claim 12, wherein said coating formulation includes a vasoconstrictor.

24. The system of claim 23, wherein said vasoconstrictor is selected from the group consisting of epinephrine, naphazoline, tetrahydrozoline indanazoline, metizoline, tramazoline, tymazoline, oxymetazoline, xylometazoline, amidephrine, cafaminol, cyclopentamine, deoxyepinephrine, epinephrine, felypressin, indanazoline, metizoline, midodrine, naphazoline, nordefrin, octodrine, ornipressin, oxymethazoline, phenylephrine, phenylethanolamine, phenylpropanolamine, propylhexedrine, pseudoephedrine, tetrahydrozoline, tramazoline, tuaminoheptane, tymazoline, vasopressin and xylometazoline.

25. The system of claim 12, wherein said coating formulation includes a pathway patency modulator.

26. The system of claim 25, wherein said pathway patency modulator is selected from the group consisting of osmotic agents, sodium chloride, zwitterionic compounds, amino acids, anti-inflammatory agents, betamethasone 21-phosphate disodium salt, triamcinolone acetonide 21-disodium phosphate, hydrocortamate hydrochloride, hydrocortisone 21-phosphate disodium salt, methylprednisolone 21-phosphate disodium salt, methylprednisolone 21-succinaate sodium salt, paramethasone disodium phosphate, prednisolone 21-succinate sodium salt, anticoagulants, citric acid, citrate salts, sodium citrate, dextran sulfate sodium, and EDTA.

27. The system of claim 12, wherein said coating formulation has a viscosity less than approximately 5 poise and greater than approximately 0.3 poise.

28. A system for transdermally delivering multiple immunologically active agents, comprising a microprojection array having a plurality of stratum corneum-piercing microprojections, said microprojection array having at least first and second array regions, said first array region having a first biocompatible coating disposed thereon, said first biocompatible coating including a first immunologically active agent, said second array region having a second biocompatible coating disposed thereon, said second biocompatible coating including a second immunologically active agent.

29. The system of claim 28, wherein said first and second immunologically active agents are different.

30. The system of claim 28, wherein said first and second immunologically active agents are selected from the group consisting of viruses, bacteria, protein-based vaccines, polysaccharide-based vaccine, and nucleic acid-based vaccines.

31. The system of claim 28, wherein said first and second immunologically active agents are selected from the group consisting of viruses, weakened viruses, killed viruses, bacteria, weakened bacteria, killed bacteria, protein-based vaccines, polysaccharide-based vaccine, nucleic acid-based vaccines, proteins, polysaccharide conjugates, oligosaccharides, lipoproteins, Bordetella pertussis (recombinant PT vaccine—

acellular), Clostridium tetani (purified, recombinant), Corynebacterium diphtheriae (purified, recombinant), Cytomegalovirus (glycoprotein subunit), Group A streptococcus (glycoprotein subunit, glycoconjugate Group A polysaccharide with tetanus toxoid, M protein/peptides linked to toxing subunit carriers, M protein, multivalent type-specific epitopes, cysteine protease, C5a peptidase), Hepatitis B virus (recombinant Pre S1, Pre-S2, S, recombinant core protein), Hepatitis C virus (recombinant—

expressed surface proteins and epitopes), Human papillomavirus (Capsid protein, TA-GN recombinant protein L2 and E7[from HPV-6], MEDI-501 recombinant VLP L1 from HPV-11, Quadrivalent recombinant BLP L1 [from HPV-6], HPV-11, HPV-16, and HPV-18, LAMP-E7[from HPV-16]), Legionella pneumophila (purified bacterial survace protein), Neisseria meningitides (glycoconjugate with tetanus toxoid), Pseudomonas aeruginosa (synthetic peptides), Rubella virus (synthetic peptide), Streptococcus pneumoniae (glycoconjugate [1, 4, 5, 6B, 9N, 14, 18C, 19V, 23F] conjugated to meningococcal B OMP, glycoconjugate [4, 6B, 9V, 14, 18C, 19F, 23F] conjugated to CRM197, glycoconjugate [1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F] conjugated to CRM1970, Treponema pallidum (surface lipoproteins), Varicella zoster virus (subunit, glycoproteins), Vibrio cholerae (conjugate lipopolysaccharide), cytomegalo virus, hepatitis B virus, hepatitis C virus, human papillomavirus, rubella virus, varicella zoster, bordetella pertussis, clostridium tetani, corynebacterium diphtheriae, group A streptococcus, legionella pneumophila, neisseria meningitdis, pseudomonas aeruginosa, streptococcus pneumoniae, treponema pallidum, vibrio cholerae, flu vaccines, Lyme disease vaccines, rabies vaccines, measles vaccines, mumps vaccines, chicken pox vaccines, small pox vaccines, hepatitis vaccines, pertussis vaccines, diphtheria vaccines, nucleic acids, single-stranded nucleic acids, double-stranded nucleic acids, supercoiled plasmid DNA, linear plasmid DNA, cosmids, bacterial artificial chromosomes (BACs), yeast artificial chromosomes (YACs), mammalian artificial chromosomes, RNA molecules, and mRNA.

32. The system of claim 28, wherein said first and second immunologically active agents include an immune response augmenting adjuvant selected from the group consisting of aluminum phosphate gel, aluminum hydroxide, alpha glucan, β

-glucan, cholera toxin B subunit, CRL1005, ABA block polymer with mean values of x=8 and y=205, gamma inulin, linear (unbranched) β

-D(2->

1) polyfructofuranoxyl-α

-D-glucose, Gerbu adjuvan, N-acetylglucosamine-(β

1-4)-N-acetylmuramyl-L-alanyl-D-glutamine (GMDP), dimethyl dioctadecylammonium chloride (DDA), zinc L-proline salt complex (Zn-Pro-8), Imiquimod (1-(2-methypropyl)-1H-imidazo[4,5-c]quinolin4-amine, ImmTher™

, N-acetylglucoaminyl-N-acetylmuramyl-L-Ala-D-isoGlu-L-Ala-glycerol dipalmitate, MTP-PE liposomes, C₅₉H₁₀₈N₆O₁₉PNa-3H₂O (MTP), Murametide, Nac-Mur-L-Ala-D-Gln-OCH₃, Pleuran, QS-21;

S-28463, 4-amino-a, a-dimethyl-1H-imidazo[4,5-c]quinoline-1-ethanol, sclavo peptide, VQGEESNDK.HCl (IL-1β

163-171 peptide), threonyl-MDP (Termurtide™

), N-acetyl muramyl-L-threonyl-D-isoglutamine, interleukine 18 (IL-18), IL-2 IL-12, IL-15, IL-4, IL-10, DNA oligonucleotides, CpG containing oligonucleotides, gamma interferon, and NF kappa B regulatory signaling proteins.

33. The system of claim 28, wherein said microprojection member has a microprojection density of at least approximately 100 microprojections/cm².

34. The system of claim 28, wherein said microprojection member has a microprojection density in the range of approximately 200-3000 microprojections/cm².

35. The system of claim 28, wherein each of said microprojections has a length in the range of approximately 50-145 microns.

36. A method for transdermally delivering multiple immunologically active agents to a subject, the method comprising the steps of:

providing a microprojection array having a plurality of microprojections, said microprojection array having at least first and second array regions;

coating said first array region with a first biocompatible coating, said first biocompatible coating including at least one immunologically active agent;

coating said second array region with a second biocompatible coating, said second biocompatible coating including an immune response augmenting adjuvant; and

applying said coated microprojection array to the skin of a subject.

37. A method for transdermally delivering multiple immunologically active agents to a subject, the method comprising the steps of:

providing a microprojection array having a plurality of microprojections, said microprojection array having a plurality of array regions;

coating at least a first microprojection in a first array region with a first biocompatible coating having a first immunologically active agent;

coating at least a second microprojection in a second array region with a second biocompatible coating having a second immunologically active agent; and

applying said coated microprojection array to the skin of a subject.

38. The method of claim 37, wherein said first and second immunologically active agents are different.