Interaction of antidepressant drug, clomipramine, with model and biological stratum corneum membrane as studied by electron paramagnetic resonance.
The 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.
Hacettepe University, Department of Physics Engineering, Ankara, 06800, Turkey.
Dilek
D
Yonar
Nuray
N
Horasan
Dilek Dadayli
DD
Paktaş
Zrinka
Z
Abramović
Janez
J
Štrancar
M Maral
MM
Sünnetçioğlu
Marjeta
M
Sentjurc
D000279:Administration, Cutaneous; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D002997:Clomipramine / Q000008:administration & dosage*; D003198:Computer Simulation; D016503:Drug Delivery Systems / Q000379:methods; D004423:Ear; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D008081:Liposomes / Q000008:administration & dosage; D008566:Membranes / Q000378:metabolism*; D008954:Models, Biological; D012867:Skin / Q000378:metabolism*; D013113:Spin Labels; D013552:Swine
D000928:Antidepressive Agents; D008081:Liposomes; D013113:Spin Labels; D002997:Clomipramine
EPR spin labeling; antidepressant; diffusion; liposomes; simulation; spectroscopy; stratum corneum; transdermal drug delivery