Efficacy of imiquimod-based transcutaneous immunization using a nano-dispersed emulsion gel formulation.
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...
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doaj-2ec1ed0436d14bf589bc00c0f12cdf932020-11-25T01:58:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10266410.1371/journal.pone.0102664Efficacy of imiquimod-based transcutaneous immunization using a nano-dispersed emulsion gel formulation.Pamela SteinKarsten GogollStefan TenzerHansjörg SchildStefan StevanovicPeter LangguthMarkus P RadsakBACKGROUND: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.http://europepmc.org/articles/PMC4099367?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pamela Stein Karsten Gogoll Stefan Tenzer Hansjörg Schild Stefan Stevanovic Peter Langguth Markus P Radsak |
spellingShingle |
Pamela Stein Karsten Gogoll Stefan Tenzer Hansjörg Schild Stefan Stevanovic Peter Langguth Markus P Radsak Efficacy of imiquimod-based transcutaneous immunization using a nano-dispersed emulsion gel formulation. PLoS ONE |
author_facet |
Pamela Stein Karsten Gogoll Stefan Tenzer Hansjörg Schild Stefan Stevanovic Peter Langguth Markus P Radsak |
author_sort |
Pamela Stein |
title |
Efficacy of imiquimod-based transcutaneous immunization using a nano-dispersed emulsion gel formulation. |
title_short |
Efficacy of imiquimod-based transcutaneous immunization using a nano-dispersed emulsion gel formulation. |
title_full |
Efficacy of imiquimod-based transcutaneous immunization using a nano-dispersed emulsion gel formulation. |
title_fullStr |
Efficacy of imiquimod-based transcutaneous immunization using a nano-dispersed emulsion gel formulation. |
title_full_unstemmed |
Efficacy of imiquimod-based transcutaneous immunization using a nano-dispersed emulsion gel formulation. |
title_sort |
efficacy of imiquimod-based transcutaneous immunization using a nano-dispersed emulsion gel formulation. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4099367?pdf=render |
work_keys_str_mv |
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