title: Efficacy of imiquimod-based transcutaneous immunization using a nano-dispersed emulsion gel formulation.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Immunology, Johannes Gutenberg-University Medical Center, Mainz, Germany.
authors.forename: Pamela
authors.initials: P
authors.lastname: Stein
authors.affiliation: Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Gogoll
authors.affiliation: Institute for Immunology, Johannes Gutenberg-University Medical Center, Mainz, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Tenzer
authors.affiliation: Institute for Immunology, Johannes Gutenberg-University Medical Center, Mainz, Germany.
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schild
authors.affiliation: Department of Immunology, Eberhard Karls-University Tübingen, Tübingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanovic
authors.affiliation: Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Langguth
authors.affiliation: Third Department of Medicine, Johannes Gutenberg-University Medical Center, Mainz, Germany.
authors.forename: Markus P
authors.initials: MP
authors.lastname: Radsak
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000279:Administration, Cutaneous; D000634:Aminoquinolines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004655:Emulsions; D005260:Female; D005782:Gels; D000077271:Imiquimod; D008297:Male; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D012869:Skin Absorption; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013945:Thymoma / Q000628:therapy; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D019496:Cancer Vaccines; D004655:Emulsions; D005782:Gels; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin; D000077271:Imiquimod