title: In vivo/ex vivo targeting of Langerhans cells after topical application of the immune response modifier TMX-202: confocal Raman microscopy and histology analysis.
abstract: The increased ability of TMX-202 (derivative of imiquimod) to penetrate the intact stratum corneum (SC) and the follicular orifices of porcine ear skin was shown ex vivo using confocal Raman microscopy and laser scanning microscopy. Moreover, to assess whether TMX-202 is able to reach the immune cells, Langerhans cells extracted from pretreated human skin were investigated ex vivo using confocal Raman microscopy combined with multivariate statistical methods. Tracking the Raman peak of dimethyl sulfoxide centered at 690  cm(−1), the absorption of TMX-202 containing formulation by Langerhans cells was shown. To answer the question whether the TMX-202 active ingredient is able to reach Langerhans cells, the attraction of immune cells to TMX-202 containing formulation treated skin was measured in the in vivo rodent model Mastomys coucha. The results show that TMX-202 active ingredient is able to reach Langerhans cells after penetrating through the intact skin and subsequently attract immune cells. Both the intercellular/transcellular as well as the follicular pathways allow the penetration through the intact barrier of the SC.
authors.affiliation: Charité-Universitätsmedizin Berlin, Department of Dermatology, Venerology, and Allergology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Maxim E
authors.initials: ME
authors.lastname: Darvin
authors.affiliation: Charité-Universitätsmedizin Berlin, Department of Dermatology, Venerology, and Allergology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Gisela
authors.initials: G
authors.lastname: Thiede
authors.affiliation: Charité-Universitätsmedizin Berlin, Department of Dermatology, Venerology, and Allergology, Charitéplatz 1, 10117 Berlin, GermanybCentro de Investigación e Innovación Tecnológica (CIITEC) del Instituto Politécnico Nacional (IPN), Cerrada de Cecati S/N, Co.
authors.forename: Saul Mujica
authors.initials: SM
authors.lastname: Ascencio
authors.affiliation: Charité-Universitätsmedizin Berlin, Department of Dermatology, Venerology, and Allergology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Schanzer
authors.affiliation: Charité-Universitätsmedizin Berlin, Department of Dermatology, Venerology, and Allergology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Richter
authors.affiliation: DKFZ-Division of Viral Transformation Mechanisms, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
authors.forename: Sabrina E
authors.initials: SE
authors.lastname: Vinzón
authors.affiliation: DKFZ-Division of Viral Transformation Mechanisms, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hasche
authors.affiliation: DKFZ-Division of Viral Transformation Mechanisms, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Rösl
authors.affiliation: Telormedix S.A, Via Lugano 13, Agno CH-6982, Switzerland.
authors.forename: Roberto
authors.initials: R
authors.lastname: May
authors.affiliation: Foamix Pharmaceuticals Ltd., 2 Holzman Street, Weizmann-Science Park, Rehovot 7670402, Israel.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Hazot
authors.affiliation: Foamix Pharmaceuticals Ltd., 2 Holzman Street, Weizmann-Science Park, Rehovot 7670402, Israel.
authors.forename: Dov
authors.initials: D
authors.lastname: Tamarkin
authors.affiliation: Charité-Universitätsmedizin Berlin, Department of Dermatology, Venerology, and Allergology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Lademann
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D020404:Glycerophospholipids / Q000494:pharmacology*; D006801:Humans; D007801:Langerhans Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018613:Microscopy, Confocal; D051189:Murinae; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D012869:Skin Absorption; D013059:Spectrum Analysis, Raman; D013552:Swine
chemical_list: D020404:Glycerophospholipids; C000590331:TMX-202; D000225:Adenine