Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 491, Issue 1-2, Pages 375-383Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2015.06.025
Keywords
Ceramic nanoporous microneedles; (Trans)dermal drug delivery; Vaccine delivery; (Anti-tumor) CD8(+) T cell response; Human skin
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Funding
- RVO The Netherlands Enterprise Agency
- Eurotransbio ETB
- ERC-Advanced
- NGI-Preseed of NWO, The Netherlands Organisation for Scientific Research
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Current vaccination technology can advance from the use of novel ceramic nanoporous microneedle arrays (npMNA), where the material serves as a storage reservoir for vaccines. Moreover, npMNA will enhance vaccine efficacy by more precisely reaching skin dendritic cells, the kickstarters of T and B cell immunity. In the present study we assessed the efficacy of vaccination using npMNAs by in vivo application of OVA(257-264) peptides mixed with agonistic anti-CD40 antibodies as adjuvant. The induction of OVA-specific CD8(+) T cells via npMNA was comparable with the frequency induced via intradermal injection using needle-syringe. However, only when expanding the vaccination area by using two npMNAs the frequencies of induced IFN-gamma-specific effector CD8(+) T cells were comparable with those induced via needle-syringe injection. Analysis of vaccine release from npMNA in a human ex vivo skin explant model revealed that OVA(257-264) peptides were indeed delivered intradermal, and release also increased by prolonging the npMNA application time on the human skin. Together, our studies demonstrate the potential of npMNA for vaccine delivery in human skin and in vivo induction of CD8(+) effector T cell responses. (C) 2015 Elsevier B.V. All rights reserved.
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