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Ovalbumin-coated pH-sensitive microneedle arrays effectively induce ovalbumin-specific antibody and T-cell responses in mice.
Eur J Pharm Biopharm 2014; 88(2):310-5EJ

Abstract

The aim of this work was to study the applicability of antigen-coated pH-sensitive microneedle arrays for effective vaccination strategies. Therefore, a model antigen (ovalbumin) was coated onto pH-sensitive (pyridine-modified) microneedle arrays to test pH-triggered antigen release by applying the coated arrays onto ex vivo human skin, and by conducting a dermal immunization study in mice. The release of antigen into ex vivo human skin from the coated microneedles was determined by using radioactively labeled ovalbumin. To investigate the induction of antigen-specific IgG, and CD4(+) and CD8(+) T-cell responses, BALB/c mice were immunized with antigen-coated pH-sensitive microneedles by the 'coat and poke' approach. These responses were compared to responses induced by the 'poke and patch' approach, and subcutaneous and intradermal vaccination with classic hypodermic needles. The pH-sensitive microneedle arrays were efficiently coated with ovalbumin (95% coating efficiency) and upon application of six microneedle arrays 4.27 of 7 μg ovalbumin was delivered into the skin, showing a release efficiency of 70%. In contrast, the 'poke and patch' approach led to a delivery of only 6.91 of 100 μg ovalbumin (7% delivery efficiency). Immunization by means of ovalbumin-coated microneedles resulted in robust CD4(+) and CD8(+) T-cell responses comparable to those obtained after subcutaneous or intradermal immunization with conventional needles. Moreover, it effectively induced IgG responses; however, it required prime-boost immunizations before antibodies were produced. In conclusion, antigen delivery into ex vivo human skin by antigen-coated pH-sensitive microneedle arrays is more efficient than the 'poke-and-patch' approach and in vivo vaccination studies show the applicability of pH-sensitive microneedles for the induction of both T cell and B cell responses.

Authors+Show Affiliations

Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands.Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden, The Netherlands.Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands.Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden, The Netherlands.Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands.Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands. Electronic address: bouwstra@lacdr.leidenuniv.nl.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24820032

Citation

van der Maaden, Koen, et al. "Ovalbumin-coated pH-sensitive Microneedle Arrays Effectively Induce Ovalbumin-specific Antibody and T-cell Responses in Mice." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 88, no. 2, 2014, pp. 310-5.
van der Maaden K, Varypataki EM, Romeijn S, et al. Ovalbumin-coated pH-sensitive microneedle arrays effectively induce ovalbumin-specific antibody and T-cell responses in mice. Eur J Pharm Biopharm. 2014;88(2):310-5.
van der Maaden, K., Varypataki, E. M., Romeijn, S., Ossendorp, F., Jiskoot, W., & Bouwstra, J. (2014). Ovalbumin-coated pH-sensitive microneedle arrays effectively induce ovalbumin-specific antibody and T-cell responses in mice. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 88(2), pp. 310-5. doi:10.1016/j.ejpb.2014.05.003.
van der Maaden K, et al. Ovalbumin-coated pH-sensitive Microneedle Arrays Effectively Induce Ovalbumin-specific Antibody and T-cell Responses in Mice. Eur J Pharm Biopharm. 2014;88(2):310-5. PubMed PMID: 24820032.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ovalbumin-coated pH-sensitive microneedle arrays effectively induce ovalbumin-specific antibody and T-cell responses in mice. AU - van der Maaden,Koen, AU - Varypataki,Eleni Maria, AU - Romeijn,Stefan, AU - Ossendorp,Ferry, AU - Jiskoot,Wim, AU - Bouwstra,Joke, Y1 - 2014/05/09/ PY - 2014/03/11/received PY - 2014/04/19/revised PY - 2014/05/02/accepted PY - 2014/5/14/entrez PY - 2014/5/14/pubmed PY - 2015/9/2/medline KW - Dermal immunization KW - Functional coatings KW - Microneedles KW - Minimally-invasive drug delivery KW - Transdermal drug delivery KW - pH-triggered delivery SP - 310 EP - 5 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 88 IS - 2 N2 - The aim of this work was to study the applicability of antigen-coated pH-sensitive microneedle arrays for effective vaccination strategies. Therefore, a model antigen (ovalbumin) was coated onto pH-sensitive (pyridine-modified) microneedle arrays to test pH-triggered antigen release by applying the coated arrays onto ex vivo human skin, and by conducting a dermal immunization study in mice. The release of antigen into ex vivo human skin from the coated microneedles was determined by using radioactively labeled ovalbumin. To investigate the induction of antigen-specific IgG, and CD4(+) and CD8(+) T-cell responses, BALB/c mice were immunized with antigen-coated pH-sensitive microneedles by the 'coat and poke' approach. These responses were compared to responses induced by the 'poke and patch' approach, and subcutaneous and intradermal vaccination with classic hypodermic needles. The pH-sensitive microneedle arrays were efficiently coated with ovalbumin (95% coating efficiency) and upon application of six microneedle arrays 4.27 of 7 μg ovalbumin was delivered into the skin, showing a release efficiency of 70%. In contrast, the 'poke and patch' approach led to a delivery of only 6.91 of 100 μg ovalbumin (7% delivery efficiency). Immunization by means of ovalbumin-coated microneedles resulted in robust CD4(+) and CD8(+) T-cell responses comparable to those obtained after subcutaneous or intradermal immunization with conventional needles. Moreover, it effectively induced IgG responses; however, it required prime-boost immunizations before antibodies were produced. In conclusion, antigen delivery into ex vivo human skin by antigen-coated pH-sensitive microneedle arrays is more efficient than the 'poke-and-patch' approach and in vivo vaccination studies show the applicability of pH-sensitive microneedles for the induction of both T cell and B cell responses. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/24820032/Ovalbumin_coated_pH_sensitive_microneedle_arrays_effectively_induce_ovalbumin_specific_antibody_and_T_cell_responses_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(14)00152-0 DB - PRIME DP - Unbound Medicine ER -