Autoren:	Stein, Pamela Gogoll, Karsten Tenzer, Stefan Schild, Hansjörg Stevanovic, Stefan Langguth, Peter Radsak, Markus
Titel:	Efficacy of imiquimod-based transcutaneous immunization using a nano-dispersed emulsion gel formulation
Online-Publikationsdatum:	19-Okt-2022
Erscheinungsdatum:	2014
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	Background: Transcutaneous immunization (TCI) approaches utilize skin associated lymphatic tissues to elicit specific immune responses. In this context, the imidazoquinoline derivative imiquimod formulated in Aldara applied onto intact skin together with a cytotoxic T lymphocyte (CTL) epitope induces potent CTL responses. However, the feasibility and efficacy of the commercial imiquimod formulation Aldara is limited by its physicochemical properties as well as its immunogenicity. Methodology/Principal Findings: To overcome these obstacles, we developed an imiquimod-containing emulsion gel (IMI- Gel) and characterized it in comparison to Aldara for rheological properties and in vitro mouse skin permeation in a Franz diffusion cell system. Imiquimod was readily released from Aldara, while IMI-Gel showed markedly decreased drug release. Nevertheless, comparing vaccination potency of Aldara or IMI-Gel-based TCI in C57BL/6 mice against the model cytotoxic T- lymphocyte epitope SIINFEKL, we found that IMI-Gel was equally effective in terms of the frequency of peptide-specific T- cells and in vivo cytolytic activity. Importantly, transcutaneous delivery of IMI-Gel for vaccination was clearly superior to the subcutaneous or oral route of administration. Finally, IMI-Gel based TCI was at least equally effective compared to Aldara- based TCI in rejection of established SIINFEKL-expressing E.G7 tumors in a therapeutic setup indicated by enhanced tumor rejection and survival. Conclusion/Significance: In summary, we developed a novel imiquimod formulation with feasible pharmaceutical properties and immunological efficacy that fosters the rational design of a next generation transcutaneous vaccination platform suitable for the treatment of cancer or persistent virus infections.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin FB 09 Chemie, Pharmazie u. Geowissensch.
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8097
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	PLoS one 9 7
Seitenzahl oder Artikelnummer:	e102664
Verlag:	PLoS
Verlagsort:	Lawrence, Kan.
Erscheinungsdatum:	2014
ISSN:	1932-6203
URL der Originalveröffentlichung:	http://dx.doi.org/10.1371/journal.pone.0102664
DOI der Originalveröffentlichung:	10.1371/journal.pone.0102664
Enthalten in den Sammlungen:	DFG-OA-Publizieren (2012 - 2017)