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Buccal Delivery of Biopharmaceuticals: Vaccines and Allergens

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Mucosal Delivery of Biopharmaceuticals

Abstract

Oral delivery of most biopharmaceuticals is limited due to their acidic and enzymatic degradation in the gastrointestinal tract. Furthermore, the high molecular weight of these drugs often results in poor absorption through the gastrointestinal membranes into the systemic circulation when administered orally. Among the new strategies for an improved therapy with biopharmaceuticals is their delivery via different routes of administration such as various mucosas (oral, nasal, vaginal, rectal, etc.) besides parenteral delivery. In this chapter, we will focus on oral mucosa as an alternative delivery route for biopharmaceuticals, specifically for vaccines and allergens, as almost all the data reported on oral mucosal delivery of biopharmaceuticals are related to recombinant vaccines and allergens.

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References

  1. Walsh G. Biopharmaceuticals: recent approvals and likely directions. Trends Biotechnol. 2005;23(11):553–8.

    Article  CAS  PubMed  Google Scholar 

  2. Walsh G. Post-translational modifications of protein biopharmaceuticals. Drug Discov Today. 2010;15(17–18):773–80.

    Article  CAS  PubMed  Google Scholar 

  3. Rader RA. What is a biopharmaceutical? Part 1: (Bio)technology-based definitions. BioExecutive International; 2005. pp. 60–5.

    Google Scholar 

  4. No authors. Federal register/ Vol. 68, No. 123/ Thursday, June 26, 2003/ Notices. http://www.fda.gov/ohrms/dockets/98fr/03–16108.pdf. Accessed 19 March 2013.

  5. No authors. Federal Register/ Vol. 70, No. 56/ Thursday, March 24, 2005/ rules and regulations. http://www.gpo.gov/fdsys/pkg/FR-2005-03-24/pdf/05-5780.pdf. Accessed 19 March 2013.

  6. No authors. Directive 2001/83/EC of the European parliament and of the Council of 6 November 2001 on the community code relating to medicinal products for human use. http://www.emea.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004481.pdf. Accessed 19 March 2013.

  7. Orive G, Gascon AR, Hernandez RM, Dominguez-Gil A, Pedraz JL. Techniques: new approaches to the delivery of biopharmaceuticals. Trends Pharmacol Sci. 2004;25(7):382–7.

    Article  CAS  PubMed  Google Scholar 

  8. Singh R, Singh S, Lillard JW. Past, present, and future technologies for oral delivery of therapeutic proteins. J Pharm Sci. 2008;97(7):2497–523.

    Article  CAS  PubMed  Google Scholar 

  9. Pather SI, Rathbone MJ, Şenel S. Current status and the future of buccal drug delivery systems. Expert Opin Drug Del. 2008;5(5):531–42.

    Article  CAS  Google Scholar 

  10. Pather SI, Rathbone MJ, Şenel S. Oral transmucosal drug delivery. In: Rathbone M, et al., editors. Modified release drug delivery technology. 2nd ed. Vol. 1, Informa Healthcare; 2008. pp. 54–73.

    Google Scholar 

  11. Şenel S, Rathbone MJ, Cansız M, Pather I. Recent developments in buccal and sublingual delivery systems. Expert Opin Drug Del. 2012;9(6):615–28.

    Article  Google Scholar 

  12. Şenel S, Kremer M, Nagy K, Squier C. Delivery of bioactive peptides and proteins across oral (buccal) mucosa. Curr Pharm Biotechnol. 2001;2(2):175–86.

    Article  PubMed  Google Scholar 

  13. Squier CA, Wertz P. Structure and function of the oral mucosa and implications for drug delivery. In: Rathbone MJ, editor. Oral mucosal delivery. New York: Marcel Dekker; 1996. pp. 1–26.

    Google Scholar 

  14. Harris D, Robinson JR. Drug delivery via the mucous-membranes of the oral cavity. J Pharm Sci. 1992;81(1):1–10.

    Article  CAS  PubMed  Google Scholar 

  15. Wertz PW, Squier CA. Cellular and molecular-basis of barrier function in oral epithelium. Crit Rev Ther Drug. 1991;8(3):237–69.

    CAS  Google Scholar 

  16. Scholz OA, Wolff A, Schumacher A, Giannola LI, Campisi G, Ciach T, Velten T. Drug delivery from the oral cavity. focus on a novel mechatronic delivery device. Drug Discov Today. 2008;13(5–6):247–53.

    Article  CAS  PubMed  Google Scholar 

  17. Arca HC, Günbeyaz M, Şenel S. Chitosan-based systems for the delivery of vaccine antigens. Expert Rev Vaccines. 2009;8(7):937–53.

    Article  CAS  PubMed  Google Scholar 

  18. Şenel S. Chitosan-based particulate systems for non-invasive vaccine delivery. Adv Polym Sci. 2011;243:111–138.

    Article  Google Scholar 

  19. Kweon MN. Sublingual mucosa: a new vaccination route for systemic and mucosal immunity. Cytokine. 2011;54 (1):1–5.

    Article  CAS  PubMed  Google Scholar 

  20. No authors. EMEA/CHMP/BWP/304831/2007guideline on allergen products: production and quality issues. http://www.emea.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003333.pdf. Accessed 19 March 2013.

  21. Cromwell O, Hafner D, Nandy A. Recombinant allergens for specific immunotherapy. J Allergy Clin Immun. 2011;127(4):865–72.

    Article  CAS  PubMed  Google Scholar 

  22. No authors. FDA—allergenics. http://www.fda.gov/BiologicsBloodVaccines/Allergenics/default.htm. Accessed 19 March 2013.

  23. Linnemann DESL. One hundred years of immunotherapy: review of the first landmark studies. Allergy Asthma Proc. 2012;33(2):122–8.

    Article  CAS  Google Scholar 

  24. Fujimura T, Okamoto Y, Taniguchi M. Therapeutic effects and biomarkers in sublingual immunotherapy: a review. J Allergy (Cairo). 2012;2012:381737.

    Google Scholar 

  25. Sikora JM, Tankersley MS. Perception and practice of sublingual immunotherapy among practicing allergists in the United States: a follow-up survey. Ann Allergy Asthma Immunol. 2013;110(3):194–197.e194.

    Google Scholar 

  26. Frati F, La Grutta S, Bernardini R, Zampogna S, Scurati S, Puccinelli P, Riario-Sforza GG, Incorvaia C. Sublingual immunotherapy: administration, dosages, use. Int J Immunopathol Pharmacol. 2009;22(4 Suppl):13–6.

    Google Scholar 

  27. Valenta R. The future of antigen-specific immunotherapy of allergy. Nat Rev Immunol. 2002;2(6):446–53.

    CAS  PubMed  Google Scholar 

  28. Moingeon P. Sublingual immunotherapy: from biological extracts to recombinant allergens. Allergy. 2006;61:15–9.

    Article  PubMed  Google Scholar 

  29. Frati F, Moingeon P, Marcucci F, Puccinelli P, Sensi L, Di Cara G, Incorvaia C. Mucosal immunization application to allergic disease. Sublingual immunotherapy. Allergy Asthma Proc. 2007;28(1):35–9.

    Article  CAS  PubMed  Google Scholar 

  30. Novak N, Bieber T, Allam JP. Immunological mechanisms of sublingual allergen-specific immunotherapy. Allergy. 2011;66(6):733–9.

    Article  CAS  PubMed  Google Scholar 

  31. Pfaar O, Cazan D, Klimek L, Larenas-Linnemann D, Calderon MA. Adjuvants for immunotherapy. Curr Opin Allergy Clin Immunol. 2012;12(6):648–57.

    Article  CAS  Google Scholar 

  32. Calderon MA, Simons FER, Malling HJ, Lockey RF, Moingeon P, Demoly P. Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile. Allergy. 2012;67(3):302–11.

    Article  CAS  PubMed  Google Scholar 

  33. Allam JP, Stojanovski G, Friedrichs N, Peng W, Bieber T, Wenzel J, Novak N. Distribution of Langerhans cells and mast cells within the human oral mucosa: new application sites of allergens in sublingual immunotherapy? Allergy. 2008;63(6):720–7.

    Article  PubMed  Google Scholar 

  34. Becker WM, Vogel L, Vieths S. Standardization of af lergen extracts for immunotherapy: where do we stand? Curr Opin Allergy Clin Immunol. 2006;6(6):470–5.

    Article  Google Scholar 

  35. Moingeon P. Adjuvants for allergy vaccines. Hum Vacc Immunother. 2012;8(10):1492–8.

    Article  CAS  Google Scholar 

  36. Kopp MV. Role of immunmodulators in allergen-specific immunotherapy. Allergy. 2011;66(6):792–7.

    Article  CAS  PubMed  Google Scholar 

  37. Razafindratsita A, Saint-Lu N, Mascarell L, Berjont N, Bardon T, Betbeder D, Van Overtvelt L, Moingeon P. Improvement of sublingual immunotherapy efficacy with a mucoadhesive allergen formulation. J Allergy Clin Immunol. 2007;120(2):278–85.

    Article  CAS  PubMed  Google Scholar 

  38. Passalacqua G, Lombardi C, Troise C, Canonica GW. Sublingual immunotherapy: certainties, unmet needs and future directions. Eur Ann Allergy Clin Immunol. 2009;41(6):163–170.

    CAS  PubMed  Google Scholar 

  39. Moingeon P, Zimmer A, Van Overtvelt L, Tourdot S, Mascarell L. Oral mucosal immunity and allergy. Rev Fr Allergol. 2010;50(3):274–6.

    Article  Google Scholar 

  40. Şenel S. Chitosan-based particulate systemsfor non-invasive vaccine delivery. Adv Polym Sci. 2011;243:111–38.

    Article  Google Scholar 

  41. No authors. Viscogel—A chitosan based adjuvant for prophylactic and therapeutic vaccination. http://cordis.europa.eu/projects/rcn/96803_en.html. Accessed 22 March 2013.

  42. Bhalla PL, Singh MB. Biotechnology-based allergy diagnosis and vaccination. Trends Biotechnol. 2008;26(3):153–61.

    Article  CAS  PubMed  Google Scholar 

  43. Bahçeciler NN, Galip N, Çobanoğlu N. Multiallergen-specific immunotherapy in polysensitized patients: where are we? Immunotherapy. 2013;5(2):183–90.

    Article  PubMed  Google Scholar 

  44. Jutel M, Jaeger L, Suck R, Meyer H, Fiebig H, Cromwell O. Allergen-specific immunotherapy with recombinant grass pollen allergens. J Allergy Clin Immunol. 2005;116(3):608–13.

    Article  CAS  PubMed  Google Scholar 

  45. Radulovic S, Wilson D, Calderon M, Durham S. Systematic reviews of sublingual immunotherapy (SLIT). Allergy. 2011;66(6):740–52.

    Article  CAS  PubMed  Google Scholar 

  46. Calderon MA, Casale TB, Togias A, Bousquet J, Durham SR, Demoly P. Allergen-specific immunotherapy for respiratory allergies. From meta-analysis to registration and beyond. J Allergy Clin Immun. 2011;127(1):30–8.

    Article  PubMed  Google Scholar 

  47. Calderon MA, del Rio PR, Demoly P. Sublingual allergen immunotherapy in children. An evidence-based overview. Rev Fr Allergol. 2012;52(1):20–5.

    Article  Google Scholar 

  48. Song JH, Nguyen HH, Cuburu N, Horimoto T, Ko SY, Park SH, Czerkinsky C, Kweon MN. Sublingual vaccination with influenza virus protects mice against lethal viral infection. Proc Nat Acad Sci U S A. 2008;105(5):1644–9.

    Article  CAS  Google Scholar 

  49. Hikono H, Miyazaki A, Mase M, Inoue M, Hasegawa M, Saito T. Induction of a cross-reactive antibody response to influenza virus M2 antigen in pigs by using a Sendai virus vector. Vet Immunol Immunopathol. 2012;146(1)92–6.

    Google Scholar 

  50. Zhang T, Hashizume T, Kurita-Ochiai T, Yamamoto M. Sublingual vaccination with outer membrane protein of Porphyromonas gingivalis and Flt3 ligand elicits protective immunity in the oral cavity. Biochem Biophys Res Commun. 2009;390(3):937–41.

    Article  CAS  PubMed  Google Scholar 

  51. Cho HJ, Kim JY, Lee Y, Kim JM, Kim YB, Chun T, Oh YK. Enhanced humoral and cellular immune responses after sublingual immunization against human papillomavirus 16 L1 protein with adjuvants. Vaccine. 2010;28(14):2598–606.

    Article  CAS  PubMed  Google Scholar 

  52. Ralli-Jain P, Tifrea D, Cheng CM, Pal S, de la Maza LM. Enhancement of the protective efficacy of a Chlamydia trachomatis recombinant vaccine by combining systemic and mucosal routes for immunization. Vaccine. 2010;28(48):7659–66.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Carmichael JR, Pal S, Tifrea D, de la Maza LM. Induction of protection against vaginal shed ding and infertility by a recombinant Chlamydia vaccine. Vaccine. 2011;29(32):5276–83.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Jenikova G, Hruz P, Andersson MK, Tejman-Yarden N, Ferreira PC, Andersen YS, Davids BJ, Gillin FD, Svard SG, Curtiss R, Eckmann L 3rd. Alpha1-giardin based live heterologous vaccine protects against Giardia lamblia infection in a murine model. Vaccine. 2011;29(51):9529–37.

    Article  CAS  PubMed  Google Scholar 

  55. Batard T, Zimmer A, Nony E, Bouley J, Airouche S, Luce S, Turfkruyer M, Tourdot S, Mascarell L, Moingeon P. Anti-inflammatory activity of sublingual immunoglobulin (SLIG) in a murine model of allergen-driven airway inflammation. Vaccine. 2012;30(38):5666–74.

    Article  CAS  PubMed  Google Scholar 

  56. Flach CF, Svensson N, Blomquist M, Ekman A, Raghavan S, Holmgren J. A truncated form of HpaA is a promising antigen for use in a vaccine against Helicobacter pylori. Vaccine. 2011;29(6):1235–41.

    Article  CAS  PubMed  Google Scholar 

  57. Negri DRM, Riccomi A, Pinto D, Vendetti S, Rossi A, Cicconi R, Ruggiero P, Del Giudice G, De Magistris MT. Persistence of mucosal and systemic immune responses following sublingual immunization, Vaccine. 2010;28(25):4175–80.

    Article  CAS  PubMed  Google Scholar 

  58. Amuguni JH, Lee S, Kerstein KO, Brown DW, Belitsky BR, Herrmann JE, Keusch GT, Sonenshein AL, Tzipori S. Sublingually administered Bacillus subtilis cells expressing tetanus toxin C fragment induce protective systemic and mucosal antibodies against tetanus toxin in mice. Vaccine. 2011;29(29–30):4778–84.

    Article  CAS  PubMed  Google Scholar 

  59. Amuguni H, Lee S, Kerstein K, Brown D, Belitsky B, Herrmann J, Keusch G, Sonenshein A, Tzipori S. Sublingual immunization with an engineered Bacillus subtilis strain expressing tetanus toxin fragment C induces systemic and mucosal immune responses in piglets. Microbes Infect. 2012;14(5):447–56.

    Article  CAS  PubMed  Google Scholar 

  60. Hervouet C, Luci C, Cuburu N, Cremel M, Bekri S, Vimeux L, Maranon C, Czerkinsky C, Hosmalin A, Anjuere F. Sublingual immunization with an HIV subunit vaccine induces antibodies and cytotoxic T cells in the mouse female genital tract. Vaccine. 2010;28(34):5582–90.

    Article  CAS  PubMed  Google Scholar 

  61. Yu M, Vajdy M. A novel retinoic acid, catechin hydrate and mustard oil-based emulsion for enhanced. cytokine and antibody responses against multiple strains of HIV-1 following mucosal and systemic vaccinations. Vaccine. 2011;29(13):2429–36.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Appledorn DM, Aldhamen YA, Godbehere S, Seregin SS, Amalfitano A. Sublingual administration of an adenovirus serotype 5 (Ad5)-based vaccine confirms toll-like receptor agonist activity in the oral cavity and elicits improved mucosal and systemic cell-mediated responses against HIV antigens despite preexisting Ad5 immunity. Clin Vaccine Immunol. 2011;18(1):150–60.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  63. Domm W, Brooks L, Chung HL, Feng CY, Bowers WJ, Watson G, McGrath JL, Dewhurst S. Robust antigen-specific humoral immune responses to sublingually delivered adenoviral vectors encoding HIV-1 Env: association with mucoadhesion and efficient penetration of the sublingual barrier. Vaccine. 2011;29(40):7080–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Bush RK, Swenson C, Fahlberg B, Evans MD, Esch R, Morris M, Busse WW. House dust mite sublingual immunotherapy: results of a US trial. J Allergy Clin Immunol. 2011;127(4):974–81.e971–7.

    Google Scholar 

  65. Kinaciyan T, Jahn-Schmid B, Radakovics A, Zwolfer B, Schreiber C, Francis JN, Ebner C, Bohle B. Successful sublingual immunotherapy with birch pollen has limited effects on concomitant food allergy to apple and the immune response to the Bet v 1 homolog Mal d 1. J Allergy Clin Immun. 2007;119(4):937–43.

    Article  CAS  PubMed  Google Scholar 

  66. Winther L, Poulsen LK, Robin B, Melac M, Malling H. Safety and tolerability of recombinant Bet v 1 (rBet v 1) tablets in sublingual immunotherapy (SLIT). J Allergy Clin Immun. 2009;123(2):S215.

    Article  Google Scholar 

  67. Nittner-Marszalska M, Fayoux E, Chartier A, Strodl-Andersen J, Kuna P. Sublingual solution for immunotherapy: comparison of three different up-dosing schedules. Rev Fr Allergol. 2013;53(2):65–72.

    Article  Google Scholar 

  68. Novembre E, Galli E, Landi F, Caffarelli C, Pifferi M, De Marco E, Burastero SE, Calori G, Benetti L, Bonazza P, Puccinelli P, Parmiani S, Bernardini R, Vierucci A. Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2004;114(4):851–7.

    Article  CAS  PubMed  Google Scholar 

  69. Smith H, White P, Annila I, Poole J, Andre C, Frew A. Randomized controlled trial of high-dose sublingual immunotherapy to treat seasonal allergic rhinitis. J Allergy Clin Immunol. 2004;114(4):831–7.

    Article  CAS  PubMed  Google Scholar 

  70. Wahn U, Tabar A, Kuna P, Halken S, Montagut A, de Beaumont O, Le Gall M, Group SS. Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2009;123(1):160–66.e163.

    Google Scholar 

  71. Wahn U, Klimek L, Ploszczuk A, Adelt T, Sandner B, Trebas-Pietras E, Eberle P, Bufe A, Group SS. High-dose sublingual immunotherapy with single-dose aqueous grass pollen extract in children is effective and safe: a double-blind, placebo-controlled study. J Allergy Clin Immunol. 2012;130(4):886–93.e885.

    Google Scholar 

  72. Horak F, Zieglmayer P, Zieglmayer R, Lemell P, Devillier P, Montagut A, Melac M, Galvain S, Jean-Alphonse S, Van Overtvelt L, Moingeon P, Le Gall M. Early onset of action of a 5-grass-pollen 300-IR sublingual immunotherapy tablet evaluated in an allergen challenge chamber. J Allergy Clin Immun. 2009;124(3):471–7.

    Article  CAS  PubMed  Google Scholar 

  73. Bozek A, Ignasiak B, Filipowska B, Jarzab J. House dust mite sublingual immunotherapy. a double-blind, placebo-controlled study in elderly patients with allergic rhinitis. Clin Exp Allergy. 2013;43(2):242–8.

    Article  CAS  PubMed  Google Scholar 

  74. Cox LS, Casale TB, Nayak AS, Bernstein DI, Creticos PS, Ambroisine L, Melac M, Zeldin RK. Clinical efficacy of 300IR 5-grass pollen sublingual tablet in a US study: the importance of allergen-specific serum IgE. J Allergy Clin Immun. 2012;130(6):1327.

    Article  CAS  PubMed  Google Scholar 

  75. Marcucci F, Sensi L, Di Cara G, Gidaro G, Incorvaia C, Frati F. Sublingual reactivity to rbEt v1 and rPhl p1 in patients with oral allergy syndrome. Int J Immunopathol Pharmacol. 2006;19(1):141–8.

    CAS  PubMed  Google Scholar 

  76. Keleş S, Karakoç-Aydıner E, Özen A, İzgi AG, Tevetoğlu A, Akkoç T, Bahçeciler NN, Barlan I. A novel approach in allergen-specific immunotherapy: combination of sublingual and subcutaneous routes. J Allergy Clin Immunol. 2011;128(4):808–15, e807.

    Google Scholar 

  77. Swamy RS, Reshamwala N, Hunter T, Vissamsetti S, Santos CB, Baroody FM, Hwang PH, Hoyte EG, Garcia MA, Nadeau KC. Epigenetic modifications and improved regulatory T-cell function in subjects undergoing dual sublingual immunotherapy. J Allergy Clin Immun. 2012;130(1):215.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100, Ankara, Turkey

    Sevda Şenel & Merve Cansız

  2. School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia

    Michael J. Rathbone

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  1. Sevda Şenel
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  2. Merve Cansız
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  3. Michael J. Rathbone
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Correspondence to Sevda Şenel .

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  1. IINFACTS - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Superior de Ciências da Saúde-Norte, CESPU, Gandra, Portugal

    José das Neves

  2. NEWTherapies Group, INEB – Instituto de Engenharia Biomédica, Porto, Portugal

    Bruno Sarmento

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Şenel, S., Cansız, M., Rathbone, M. (2014). Buccal Delivery of Biopharmaceuticals: Vaccines and Allergens. In: das Neves, J., Sarmento, B. (eds) Mucosal Delivery of Biopharmaceuticals. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-9524-6_6

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