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Comparative transcutaneous immunization with imiquimod‐containing ointments and potential of in vitro methods to predict effects
Author(s) -
Gogoll Karsten,
Stein Pamela,
Wei Hai,
Schild Hansjörg,
Radsak Markus,
Langguth Peter
Publication year - 2012
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.1787
Subject(s) - in vivo , permeation , imiquimod , chemistry , pharmacology , ex vivo , transdermal , in vitro , chromatography , membrane , medicine , immunology , biochemistry , biology , microbiology and biotechnology
ABSTRACT This work evaluates the transcutaneous in vitro and in vivo immunization efficacy of five commercially available 5% imiquimod containing formulations. The parameters included microscopic analysis, rheological properties, drug permeation across synthetic membranes of molecular weight cutoff 10 kDa and ablated murine skin with both 0.1 m HCl and a phthalate buffer pH 3.6 Ph.Eur./methanol 3/7 (v/v) as receiver solutions in a Franz‐diffusion cell model. For in vivo formulation characterization, the cytotoxic T‐cell activity and interferon‐γ production in C57BL/6 mice was determined ex vivo 24 h after transcutaneous administration. OVA 257−264 (SIINFEKL) from chicken albumin served as a target antigen. Microscopic images demonstrated differences with respect to the presence or absence of crystalline API. Rheological properties point to a roughly ten‐fold difference between the products at low shear rates. With regard to drug permeation across synthetic membranes, only ‘Nan Bo’ demonstrated equality compared with Aldara™, resulting in f1 and f2 values of 5.25 and 59.58, respectively. The drug permeation rates were maximum from Aldara™ across ablated murine skin. Furthermore, differentiation between the formulations containing crystalline and dissolved states of active imiquimod was possible using this model. The in vivo results yielded significant immunomodulating activities ( p < 0.05) of multisource formulations compared with the untreated control group, however, the significance of differences between the formulations was dependent on the parameter of interest. A correlation plot of skin permeation versus in vivo immunostimulating activity yielded a slope significantly different from zero only in the case of the murine skin setup ( r between 0.421 and 0.669). Yet this correlation is deemed not satisfactory for formulation optimization. Copyright © 2012 John Wiley & Sons, Ltd.