Yonar, DilekHorasan, NurayPaktas, Dilek DadayliAbramovic, ZrinkaStrancar, JanezSunnetcioglu, M. MaralSentjurc, Marjeta2024-09-292024-09-2920130022-35491520-6017https://doi.org/10.1002/jps.23687https://hdl.handle.net/20.500.14619/3708The interactions of tricyclic antidepressant drug, clomipramine (CLO), with pig ear stratum corneum (SC) and model membranes were investigated by electron paramagnetic resonance (EPR) spin labeling to get some insight into the possible application of this drug in transdermal delivery. The changes in membrane characteristics caused by CLO in the regions that are close to the water-lipid interfaces and the central parts of the membranes were searched. The experimental results were supported by computer simulation of EPR spectra, which showed heterogeneity of the membranes composed of regions with different fluidity characteristics. CLO was effective in both parts of the layers, indicating intercalation of the drug into model membranes as well as into the pig ear SC. Introduction of various molar ratios of CLO caused a decrease in the order parameter and an increase in the rotational diffusion of nitroxide moiety in different membrane regions as well as an increase in the polarity of spin probe environment. It also changed the number of resolved spectral components, which reflects the heterogeneity of the membrane. The fluidizing effect of CLO on pig ear SC throughout the whole membrane layers indicates that CLO penetrates into the SC, which is important for its transdermal delivery. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3762-3772, 2013eninfo:eu-repo/semantics/closedAccessEPR spin labelingspectroscopystratum corneumliposomesantidepressanttransdermal drug deliverydiffusionsimulationArticle10.1002/jps.236872-s2.0-8488382523237721023925997Q23762102WOS:000324314200027Q2