Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-8097
Authors: | Stein, Pamela Gogoll, Karsten Tenzer, Stefan Schild, Hansjörg Stevanovic, Stefan Langguth, Peter Radsak, Markus |
Title: | Efficacy of imiquimod-based transcutaneous immunization using a nano-dispersed emulsion gel formulation |
Online publication date: | 19-Oct-2022 |
Year of first publication: | 2014 |
Language: | english |
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: | 610 Medizin 610 Medical sciences |
Institution: | Johannes Gutenberg-Universität Mainz |
Department: | FB 04 Medizin FB 09 Chemie, Pharmazie u. Geowissensch. |
Place: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-8097 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | PLoS one 9 7 |
Pages or article number: | e102664 |
Publisher: | PLoS |
Publisher place: | Lawrence, Kan. |
Issue date: | 2014 |
ISSN: | 1932-6203 |
Publisher URL: | http://dx.doi.org/10.1371/journal.pone.0102664 |
Publisher DOI: | 10.1371/journal.pone.0102664 |
Appears in collections: | DFG-OA-Publizieren (2012 - 2017) |
Files in This Item:
File | Description | Size | Format | ||
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![]() | efficacy_of_imiquimodbased_tr-20220925171531066.pdf | 1.07 MB | Adobe PDF | View/Open |