Mucosal delivery of vaccines: Role of mucoadhesive/biodegradable polymers

Recent Patents on Drug Delivery and Formulation

Volumn 4, Issue 2, 2010, Pages 114-128

  Garg, Neeraj K ^a,b   Mangal, Sharad ^a   Khambete, Hemant ^b   Sharma, Pradeep K ^c   Tyagi, Rajeev K ^c  

^a DR H S GOUR UNIVERSITY   (India)

^b Smriti College of Pharmaceutical Education   (India)

^c CH CHARAN SINGH UNIVERSITY   (India)

Author keywords

Immunity; Mucosal vaccine; Patents; Polymers; SIgA

Indexed keywords

ALGINIC ACID; CARBOMER; CHITOSAN; CYANOACRYLATE; EUDRAGIT; GELATIN; HYALURONIC ACID; MACROGOL; NANOPARTICLE; POLY(3 HYDROXYBUTYRIC ACID); POLY(ORTHO ESTER); POLYACRYLIC ACID; POLYANHYDRIDE; POLYCAPROLACTONE; POLYGLACTIN; POLYLACTIC ACID; POLYMER; POLYSTYRENE; POLYVINYL ALCOHOL; PULLULAN; VACCINE;

ARTICLE; BIOCOMPATIBILITY; BIODEGRADABILITY; CHEMICAL ANALYSIS; CHEMICAL COMPOSITION; CHEMICAL STRUCTURE; DRUG ABSORPTION; DRUG DELIVERY SYSTEM; DRUG FORMULATION; DRUG HALF LIFE; DRUG SOLUBILITY; HUMAN; HYDROPHOBICITY; IMMUNOGENICITY; MUCOADHESION; PARTICLE SIZE; PATENT; PH; PRIORITY JOURNAL; STRUCTURE ANALYSIS; VACCINE PRODUCTION;

ADHESIVENESS; ANIMALS; ANTIGENS; DRUG CARRIERS; HUMANS; IMMUNITY, MUCOSAL; MUCOUS MEMBRANE; PATENTS AS TOPIC; POLYMERS; VACCINES;

EID: 77954081810     PISSN: 18722113     EISSN: None     Source Type: Journal    
DOI: 10.2174/187221110791185015     Document Type: Article

References (137)

1. Sally B, Ronald BM, Eduardo F-C. Calculating the potential epidemic-level impact of therapeutic vaccination on the San Francisco HIV epidemic. AID Science 2003; 3 (21).
2. Levine MM, Campbell JD. Mucosal immunization and needle-free injection devices. In: Levine MM, Kaper JB, Rappuoli R, Liu MA, Good MF, Eds. New Generation Vaccines. Marcel Dekker Inc.: New York 2004; 393-9.
3. Glenn GM, Kenney RT, Hammond SA, Ellingsworth LR. Transcutaneous immunization and immunostimulant strategies. Immunol Allergy Clin North Am 2003; 23: 787-813.
4. Bennett JV, Fernandez de Castro J, Valdespino-Gomez JL, Garcia-Garcia Mde L, Islas-Romero R, Echaniz-Aviles G, et al. Aerosolized measles and measles-rubella vaccines induce better measles antibody booster responses than injected vaccines: Randomized trials in Mexican schoolchildren. Bull World Health Organ Suppl 2002; 80: 806-12.
5. World Health Organization, Immunization, Vaccines and Biologicals, http://www.who.int/immunization/newsroom/amcs/ en/index.html (Accessed August 25, 2009).
6. Gavi A. More combination vaccines needed: Faced with a bigger than expected Short fall in supplies of some vaccines, countries mustmake choices,PhyllidaBrown eports.http:// www.gavialliance.org/Resources_Documents/Immunization_Focus /Download/report_2.ph p (Accessed August 22, 2009).
7. Davis SS. Nasal vaccines. Adv Drug Deliv Rev 2001; 51: 21-42.
8. Nugent J, Po AL, Scott EM. Design and delivery of non-parenteral vaccines. J Clin Pharm Ther 1998; 23(4): 257-85.
9. Jaganathan KS, Vyas SP. Strong systemic and mucosal immune responses to surface modified PLGA microspheres containing recombinant hepatitis B antigen administered intranasally. Vaccine 2006; 24 (19): 4201-11.
10. Gupta PN, Mahor S, Rawat A, Khatri K, Goyal A, Vyas SP. Lectin anchored stabilized biodegradable nanoparticles for oral immunization: 1. Development and in vitro evaluation. Int J Pharm 2006; 318: 163-73.
11. O'Hagan DT. The intestinal uptake of particles and the implications for drug and antigen delivery. J Anat 1996; 189: 477-82.
12. Dea-Ayuela MA, Rama-Iniguez S, Torrado-Santiago S, Bolas- Fernandez F. Microcapsules formulated in the enteric coating copolymer Eudragit L100 as delivery systems for oral vaccination against infections by gastrointestinal nematode parasites. J Drug Target 2006; 14: 567-75.
13. Tafaghodi M, Sajadi Tabasi SA, Jaafari MR. Formulation, characterization and release studies of alginate microspheres encapsulated with tetanus toxoid. J Biomater Sci Polym Ed 2006; 17: 909-24.
14. Sturesson C, Degling WL. Comparison of poly (acryl starch) and poly (lactide-co-glycolide) microspheres as drug delivery system for a rotavirus vaccine. J Control Release 2000; 68: 441-50.
15. Litwin A, Flanagan M, Entis G, Esch K, Gartside P, Michael JG. Immunologic effects of encapsulated short ragweed extract: A potent new agent for oral immunotherapy. Ann Allergy Asthma Immunol 1996; 77: 132-38.
16. Haining WN, Anderson DG, Little SR, von Bergwelt-Baildon MS, Cardoso AA, Alves P, et al. pH-triggered microparticles for peptide vaccination. J Immunol 2004; 173: 2578-85.
17. Brandtzaeg P. Developement and basic mechanisms of human gut immunity. Nutr Rev 1998; 1993: S5-S18.
18. Guy-Grand D, Griscelli C, Vassalli P. The gut-associated lymphoid system: Nature and properties of the large dividing cells. Eur J Immunol 1974; 4: 435-43.
19. Roux ME, McWilliams M, Phillips-Quagliata JM, Lamm ME. Differentiation pathways of Peyer's patch precursors of IgA plasma cells in the secretory immune system. Cell Immunol 1981; 61: 141-53.
20. Butcher EC, William M, Youngman K, Rott L, Briskin M. Lymphocyte trafficking and regional immunity. Adv Immunol 1999; 72: 209-53.
21. Berlin C, Berg EL, Briskin MJ. 4 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MADCAM-1. Cell 1993; 74: 185-95.
22. Sonoda E, Matsumoto R, Hitoshi Y. Transforming growth factor beta induces IgA production and acts additively with interleukin-5 for IgA production. J Exp Med 1989; 170: 1415-20.
23. McIntyre TM, Kehry MR, Snapper CM. Novel in vitro model for high rate of IgA class switching. J Immunol 1995; 154: 3156-61.
24. Spalding DM, Williamson SI, Koopman WJ, McGhee JR. referential induction of polyclonal IgA secretion by murine Peyer's patch dendritic cell T cell mixtures. J Exp Med 1984; 160: 941-6.
25. Holmgren J, Czerkinsky C, Eriksson K, Mharandi A. Mucosal immunization and adjuvants: A brief overview of recent advances and challenges. Vaccine 2003; 21: S89-S95.
26. Andrianov AK, Payne LG. Polymeric carriers for oral uptake of microparticulates. Adv Drug Deliv Rev 1998; 34: 155-70.
27. Bacon A, Makin J, Sizer PJ, Jabbal-Gill I, Hinchcliffe M, Illum L, et al. Carbohydrate biopolymers enhance antibody responses to mucosally delivered vaccine antigens. Infect Immun 2000; 68:5764-70.
28. Bertram U, Bernard MC, Haensler J, Maincent P, Bodmeier R. In situ gelling nasal inserts for influenza vaccine delivery. Drug Dev Ind Pharm 2009; In press.
29. Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, Bonasio R, et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2001; 2: 361-7.
30. Payne LG, Jenkins SA, Andrianov A, Roberts BE. Water Soluble Phosphazene Polymers for Parenteral and Mucosal Vaccine Delivery. In: Powell MF, Newman MJ, Eds. Vaccine Design: The Subunit and Adjuvant Approach. Plenum Press: New York 1995; 473-92.
31. Dea-Ayuela MA, Rama-Iniguez S, Torrado-Santiago S, Bolas- Fernandez F. Microcapsules formulated in the enteric coating copolymer Eudragit L100 as delivery systems for oral vaccination against infections by gastrointestinal nematode parasites. J Drug Target 2006; 14: 567-75.
32. Tafaghodi M, Tabasi SSA, Jaafari MR. Formulation, characterization and release studies of alginate microspheres encapsulated with tetanus toxoid. J Biomater Sci Polym Ed 2006; 17: 909-24.
33. Sturesson C, Degling WL. Comparison of poly (acryl starch) and poly (lactide-co-glycolide) microspheres as drug delivery system for a rotavirus vaccine. J Control 2000; 68: 441-50.
34. Litwin A, Flanagan M, Entis G, Gottschlich G, Esch R, Gartside P, et al. Immunologic effects of encapsulated short ragweed extract: A potent new agent for oral immunotherapy. Ann Allergy Asthma Immunol 1996; 77: 132-8.
35. Haining WN, Anderson DG, Little SR, von Berwelt-Baildon MS, Cardoso AA, Alves P, et al. pH-Triggered microparticles for peptide vaccination. J Immunol 2004; 173: 2578-85.
36. Mohapatra, S.S., Kumar, M., Huang, S.K., Leong, K. Gene expression vaccine. US7118888 (2006).
37. Watts, P.J, Illum, L. Pharmaceutical compositions of chitosan with type-A gelatin. US20026465626 (2002).
38. Davis, S.S, Lin, W., Bignotti, F., Ferruti, P. Conjugate of polyethylene glycol and chitosan. US6730735 (2004).
39. Illum, L., Chatfield, S.N. Vaccine compositions including chitosan for intranasal administration and use thereof. US6391318 (2002).
40. Fernandez, A., Jose, M., Kevin, J., Csaba, N. Nanoparticles of chitosan and polyethyleneglycol as a system for the administration of biologically-active molecules. US20080095810 (2008).
41. Del, G.G., Barbara, B. Mucosal vaccines with chitosan adjuvant and meningococcal antigens. US20060051378 (2006).
42. Makin, J., Catherin, B., Andrew, D. Influenza vaccine composition with chitosan adjuvant. US6534065 (2003).
43. Alonso, F.J., Janes, K., Csaba, N. Nanoparticles of chitosan and polyethyleneglycol as a system for the administration of biologically-active molecules. US2008095810 (2008).
44. Guidice, G.D., Baudner, B. Mucosal vaccines with chitosan adjuvant and meningococcal antigens. US20060051378 (2006).
45. Illum, L.C., Steven, N. Vaccine compositions including chitosan for intranasal administration and use thereof. US7323183 (2008).
46. Giudice, G.D., Baudner, B., O'hagan, D. Mucosal meningococcal vaccine. US20070207090 (2007).
47. Bowersock, T.L., Park, K., Porter, R.E. Alginate-based vaccine compositions. US5674495 (1997).
48. Gombotz, W.R., Mumper, R.J., Hoffman, A.S. Methods and compositions for the oral delivery of therapeutic agents. US5451411 (1995).
49. Jeong, S.Y., Chan, K.I., Ae, P.J. Vaccine compositions using antigens encapsulated within alginate microspheres for oral administration and preparation process thereof. WO01000233 (2001).
50. Sava, G., Zorzin, L. Polysaccharide double-layer microcapsules as carriers for biologically active substance oral administration. US2006228422 (2006).
51. Biegajski, J.E. Two-phase mucoadhesive composition. US20070298087 (2007).
52. Chang, R.C., Kivirikko, K.I., Neff, T.B., Olsen, D.R., Polarek, J.W. Recombinant gelatin in vaccines. EP2011874 (2009).
53. Lawter, J.R. Mucoadhesi vetetracy cline formulations. US20090098203 (2009).
54. Pilch, S., Masters, J.G., Dillon, R., Viscio, D.B. Controlled surface gellingof mucoadhesive polymers on oral mucosa. US20090068259 (2009).
55. Jacob, J.S., Moslemy, P., Nangia, A., Shaked, Z., Kreitz, M. Mucoadhesive oral formulations of high permeability, high solubility drugs. US20070281007 (2007).
56. O'Hagan, D. Pavesio, A. Use of hyaluronic acid polymers for mucosal delivery of vaccine antigens and adjuvants. US6824793 (2005).
57. Weiner, D.B., Wang, B., Ugen, K.E. Methods of inducing mucosal immunity. US7220728 (2007).
58. Dehazya, P., Lu, C. Sodiumh hyaluronate microspheres. US6969531 (2005).
59. Gerber, J.D. Adjuvant composition for mucosal and injection delivered vaccines. US6676958 (2004).
60. McCluskie, M.J. Methods and products for inducing mucosal immunity. EP1733735 A2 (2006).
61. Baker, J.R. Bielinska, A., Myc, A. Nanoemulsion vaccine. US20080181949A1 (2008).
62. Mohapatra, S., Lee, D.W. Controlled and sustained gene transfer mediated by thiol-modified polymers. WO2007086923 (2007).
63. Hilgers, L. Polyanionic polymers as adjuvants for mucosal immunization. US2003021793 (2003).
64. Elisseeff, J. Biological adhesive. US20100003329 (2010).
65. Berkland, C.J., Shi, L. Nanoclusters for delivery of therapeutics. US7651770 (2010).
66. Cipolla, D.C., Blanchard, J. Dual action, inhaled formulations providing both an immediate and sustained release profile. US20090269396 (2009).
67. O'Hagan, D.T. Immunogenic compositions containing microparticles comprising adsorbed toxoid and polysaccharide- containing antigens. US20050118275 (2005).
68. Burnett, P.R., Van Hamont, J.E., Reid, R.H., Setterstrom, J.A., Van Cott, T.C., Birx, D.L. Vaccines against intracellular pathogens using antigens encapsulated within biodegradble-biocompatible microspheres. US5762965 (1998).
69. O'Hagan, D., Singh, M., Ott, G. Microparticles with adsorbent surfaces, methods of making same, and uses thereof. US20056884435 (2005).
70. Reid, R., Setterstrom, J., Boedeker, E., Vanhamont, J., Mcqueen, C., Cassels, F. Vaccines against diseases caused by enteropa- thogenic organisms using antigens encapsulated within biode- gradable-biocompatible microspheres. US20030161889 (2003).
71. Singh, M., O'Hagan, D. Use of bioadhesives and adjuvants for the mucosal delivery of antigens. US2005281843 (2005).
72. Sokoll, K.K., Chong, P., Klein, M.H. Biodegradable targetable microparticle delivery system. US20050163745 (2005).
73. O'Hagan, D., Singh, M., Klinman, D.M. Immunogenic compo- sitions containing anthrax antigen, biodegradable polymer microparticles, and polynucleotide-containing immunological adjuvant. US20080317784 (2008).
74. Ghayur, T., Morgan-lappe, S.E., Reilly, E.B., Kingsbury, G.A., Phillips, A., Wang, J., Bell, R.L., Norvell, S.M., Li, Y., Liu, J., Ying, H. Dual variable domain immumoglobulins and uses thereof. US20100076178 (2010).
75. O'hagan, D., Van Nest, G., Ott, G. S., Barackman, J., Kazzaz, J. Use of microparticles with adsorbed antigen to stimulate immune responses. US20100021548 (2010).
76. Ni, Y., Yates, K.M. Delivery of physiological agents with in situ gels comprising anionic polysaccharides. US7494669 (2009).
77. Blizzard, C.D., Rashba-step, J., Scott, T.L., Brown, L.R., Riske, F. J. Sustained release microspheres. EP1837018B1 (2010).
78. Hoffmann, E., Hoffmann, M., Horres, R. Biodegradable vascular support. US20100076544 (2010).
79. Mccarthy, S.P., Koroskenyi, B., Nicolosi, R. J. Polysaccharide- containing block copolymer particles and uses thereof. US20100040883 (2010).
80. Orlowski, M. Coated expandable system. US20100076542 (2010).
81. Lichter, J., Vollrath, B., Duron, S.G., Lebel, C., Plu, F., Ye, Q., Dellamary, L.A., Trammel, A.M., Scaife, M.C., Harris, J.P. Controlled release compositions for modulating free-radical induced damage and methods of use thereof. US20100022661 (2010).
82. Darvari, R., Lambert, A., Rashba-step, J. E.,Yang X, M., Zhang, J., O'connell, E. Methods of processing compositions containing microparticles. US20100047248 (2010).
83. Baker Jr, J.R., Bielinska, A.U., Mank, N.J., Makidon, P.E., Cao, Z., Scott, A.J., Nigavekar, S.S. Immunogenic compositions comprising nanoemulsion and hepatitis b virus immunogen and methods of using the same. US20100028433 (2010).
84. Janes KA, Fresneau MP, Marazuela A, Fabra A, Alonso MJ. Chitosan nanoparticles as delivery systems for doxorubicin. J Control Release 2001; 73: 255-67.
85. Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro-and nanoparticles in drug delivery. J Control Release 2004; 100: 5-28.
86. Dodane V, Vilivalam VD. Pharmaceutical applications of chitosan. Pharm Sci Technol Today 1998; 1: 246-53.
87. Goyal AK, Khatri K, Mishra N, Vyas SP. New patents on mucosal delivery of vaccines. Exp Opin Ther Pat 2008; 18:1271-88.
88. Alpar HO, Somavarapu S, Atuah KN, Bramwell VW. Biodegradable mucoadhesive particulates for nasal and pulmonary antigen and DNA delivery. Adv Drug Deliv Rev 2005; 57 (3): 411-30.
89. Illum L, Chatfield SN, Roberts M. Carbohydrate biopolymers enhance antibody responses to mucosally delivered vaccine antigens. Infect Immun 2000; 68: 5764-70.
90. Del, G., Giuseppe, C.S., Barbara, C.S., O'Hagan, D.T. Mucosal vaccines with chitosan adjuvant and/or meningococcal antigens. EP1506008 (2009).
91. Alonso, F., Janes, K, Csaba, N. Nanoparticles of chitosan and polyethyleneglycol as a system for the administration of biolo- gically-active molecules. WO2006097558 (2006).
92. Tafaghodi M, Sajadi TSA, Jaafari MR. Formulation, characterization and release studies of alginate microspheres encapsulated with tetanus toxoid. J Biomater Sci Polym Ed 2006; 17: 909-24.
93. Goosen, M.F.A., O'Shea, G.M, Sun, A.M.F. Microencapsulation of living tissue and cells. US4806355 (1989).
94. Gombotz, W.R., Mumper, R.J. Methods and compositions for the oral delivery of therapeutic agents. US5451411 (1995).
95. Balthasar S, Michaelis K, Dinauer N, Briesen von H, Kreuter J, Langer K. Preparation and characterization of antibody modified gelatin nanoparticles as drug carrier system for uptake in lymphocytes. Biomaterials 2005; 26: 2723-32.
96. Spear, J.M. Small particle drug compositions. WO006282 (1991).
97. Singh M, Briones M, O'Hagan DT. A novel bioadhesive intranasal delivery system for inactiveated influenzavaccines. J Control Release 2001; 70: 267-76.
98. O'Hagan, D.T., Pavesio, A. Use of hyaluronic acid polymers for mucosal delivery of vaccine and adjuvants. US20050226937 (2005).
99. Wolf BW, Garleb KA, Choe YS, Humphrey PM, Makiet KC. Pullulan is a slowly digested carbohydrate in humans. J Nutr 2003; 133: 1051-5.
100. Varner, S.E., Beeley, N.R.F., Chudzik, S.J., Burkstrand, M.J. in vivo Formed matrices including natural biodegradale polysaccharides and ophthalmic uses thereof. US20070071792 (2007).
101. Gerber, J.D. Adjuvant composition for mucosal and injection delivered vaccines. US6676958 (2004).
102. See, J.R., See, D.M. Method for inducing a systemic immune response to an antigen. US20006015576 (2000).
103. Kumar N, Langer RS, Domb AJ. Polyanhydrides: An overview. Adv Drug Deliv Rev 2002; 54: 889-910.
104. Scopelianos AG. Polyphosphazenes as New Biomaterials. In: Shalaby SW, Ed. Biomedical Polymers: Designed-to-degrade systems. Hanser/Gardner Pub, Inc.: Cincinnati, OH 1994; 153-71.
105. Vandorpe J, Schacht E, Stolnik S, Garnett MC, Davies MC, Illum L, et al. Poly(organo phosphazene) nanoparticles surface modified with poly(ethylene oxide). Biotechnol Bioeng 1996; 52: 89-95.
106. Veronese FM, Marsilio F, Caliceti P, De Filiis P, Giunchedi P, Lora S. Polyorganophosphazene microspheres for drug release: Polymer synthesis, microsphere preparation, in vitro and in vivo naproxen release. J Control Release 1998; 52: 227-37.
107. Passi P, Zadro A, Marsilio F, Lora S, Caliceti P, Veronese FM. Plain and drug loaded polyphosphazene membranes and microspheres in the treatment of rabbit bone defects. J Mater Sci Mater Med 2000; 11: 643-54.
108. Laurencin CT, Koh HJ, Neenan TX, Allcock HR, Langer R. Controlled release using a new bioerodible polyphosphazene matrix system. J Biomed Mater Res 1987; 21: 1231-46.
109. Andrianov, A.K., Decollibus, D.P., Gillis, H.A., Kha, H.H., Marin, A. Immunostimulating polyphosphazene compounds for intradermal immunization. US20090041810 (2009).
110. Gupta RK, Singh M, O'Hagan DT. Poly(lactide-co-glycolide) microparticles for the development of single-dose controlled- release vaccines. Adv Drug Deliv Rev 1998; 32: 225-46.
111. Delgado A, Lavelle EC, Hartshorne M, Davis SS. PLG microparticles stabilized using enteric coating polymers as oral vaccine delivery systems. Vaccine 1999; 17: 2927-38.
112. O'Hagan, D.T., Nest, G.V., Ott, G.S., Barackman, J., Kazzaz, J. Use of microparticles with adsorbed antigen to stimulate immune responses. US0049298 (2003).
113. Lee, H., Choi, N., Kim, M., Kim, M.-J., Kim, S.-H. Single-shot vaccine formulation. US5753234 (1998).
114. Kohn J, Langer R. Bioresorbable and bioerodible materials. Biomaterials Academic Press: San Diego 1996.
115. Grandfils, C., Jerome, R., Nihant, N. Biocompatible and biodegradable nanoparticles designed for proteinaceous drugs absorption and delivery. US5962566 (1999).
116. O'Hagan, D.T. Immunogenic compositions containing microparticles comprising adsorbed toxoid and polysaccharide- containing antigens. US2005118275 (2005).
117. Lherm C, Muller RH, Puisieux F, Couvreur P. Alkylcyanoacrylate drug carriers 2. Cytotoxicity of cyanoacrylate nanoparticles with different alkyl chainlength. Int J Pharm 1992; 84: 13-22.
118. Couvreur, P., Roland, M., Speiser, P. Biodegradable submicroscopic particles containing a biologically active substance and compositions containing them. US4329332 (1982).
119. Al-Khouri FN, Roblot-Treupel L, Fessi H, Devissaguet JP, Puisieux F. Development of a new process for the manufacture of polyisobutylcyanoacrylate nanocapsules. Int J Pharm 1986; 28: 125-32.
120. Chouinard F, Kan FWK, Leroux, JC, Foucher C, Lenaerts V. Preparation and purification of polyisohexylcyanoacrylate nanocapsules. Int J Pharm 1991; 72: 211-7.
121. Muller RH, Lherm C, Jaffray P, Couvreur P. Toxicity of cyanoacrylate particles in L929 fibroblast cell-cultures-relation between toxicity and in vitro characterization parameters. Arch Der Pharmazi 1988; 321: 681-1.
122. Askill, I.N., Byram, M.M., Greff, R.J. Application of cyanoacrylate/anti-microbial compositions to the peri-wound or peri-mucosal area. US6001345 (1999).
123. Bobo, J.S., Quintero, J.A., Jonn, J.Y., Barefoot, J.B., Clark, J.G., Narang, U., Cannizaro, S.M. Biocompatible polymers and adhesives: Compositions, methods of making and uses related thereto. US7255874 (2007).
124. Park H, Robinson JR. Mechanisms of mucoadhesion of poly (acrylic acid) hydrogels. Pharm Res 1987; 4: 457-64.
125. Ponchel G, Irache JM. Specific and non-specific bioadhesive particulate systems for oral delivery to the gastrointestinal tract. Adv Drug Deliv Rev 1998; 34: 191-219.
126. Allen A, Bell A, Mantle M, Pearson JP. The Structure and Physiology of Gastrointestinal Mucus. In: Chantler EN, Elder JB, Elstein M, Eds. Mucin in Health and Disease. Plenum Press: New York 1982; 15-133.
127. Lehr CM. Lectin-mediated drug delivery: The second generation of bioadhesives. J Control Release 2000; 65: 19-29.
128. Saffran M, Kumar GS, Savariar C, Burnham JC, Williams F, Neckers DC. A new approach to the oral administration of insulin and other peptide drugs. Science 1986; 233:1081-4.
129. Brondsted H, Kopecek J. Hydrogels for site-specific drug delivery to the colon in vitro and in vivo degradation. Pharm Res 1992; 9: 1540-5.
130. Yeh PY, Berenson MM, Samowitz WS, Kopeckova P, Kopecek J. Site specific drug-delivery and penetration enhancement in the gastrointestinal-tract. J Control Release 1995; 36: 109-24.
131. Hilgers, L. Polyanionic polymers as adjuvants for mucosal immunization. EP0934077 (2007).
132. Gerber, J.D. Adjuvant compositions and methods for delivering vaccines. US20080292663 (2008).
133. Veronese FM, Largajolli R, Boccu E, Benassi CA, Schiavon O. Surface modification of proteins: Activation of monomethoxy- polyethylene glycols by phenylchloroformates and modification of ribonuclease and superoxide dismutase. Alied Biochem Biotechnol 1985; 11: 141-52.
134. Gemeinhart RA. Polymeric systems for oral protein and peptide delivery. Pharmaceutical biotechnology. Taylor & Francis Group: LLC 2006; 283-306.
135. Compans, R.W. Methods and compositions for administering DNA to mucosal surfaces. US20030092665 (2003).
136. Jon, S., Farokhazd, O.C., Langer, R.S., Cheng, J. Coated controlled release polymer particles as efficient oral delivery vehicles for biopharmaceuticals. US20080268063 (2008).
137. McGhee JR, Mestecky J, Dertzbaugh MT, Eldridge JH, Hirasawa M, Kiyono H, et al. The mucosal immune system: From funda- mental concepts to vaccine development. Vaccine 1992; 10: 75-88.