Comparison of the tissue affinity of glucocorticoids to human lung, nasal and skin tissue in vitro

High affinity binding of topically applied glucocorticoids to their target tissues is the basis for prolonged action of the drug and reduces efflux in to the systemic circulation that might account for adverse effects. Since l ittle information on the accumulation and depletion of glucocorticoids to t issues of therapeutic interest is available the binding behavior of differe nt glucocorticoids to human lung, nasal and skin tissue is now evaluated an d drug concentrations in different tissues are compared. Furthermore, the r ole of tissue lipids and proteins in glucocorticoid binding is investigated . Therefore, sliced human lung, nasal and skin tissues are incubated with glu cocorticoid containing buffers and time course of adsorption and desorption is monitored. Two model glucocorticoids, the highly lipophilic fluticasone propionate (CAS 80474-14-2) and the rather hydrophilic hydrocortisone (CAS 50-23-7) are compared respecting their binding to native and lipid-deplete d tissues. While total adsorption rates to different tissues were highly co mparable for each glucocorticoid the observed initial desorption was clearl y different. Highest initial depletion was seen for lung tissue, lowest for skin tissue. After Initial depletion a prolonged desorption of very low co ncentrations Is observed for all tissues. Lipid depletion of tissues did ne ither change accumulation not depletion behavior except that about twice as high concentrations were bound and depleted, probably due to protein denat uration. It is concluded that glucocorticoids primarily bind to protein components o f human lung, nasal and skin tissues. Connective tissue proteins are discus sed to bind glucocorticoids with higher affinity than other protein compone nts, thus preventing high initial release rates. While total amounts of ads orption to different tissues are equivalent and initial desorption of gluco corticoids from saturated tissues varies, highest total remaining concentra tions should be observed in skin tissue followed by nasal and lung tissue. Although tissue lipids seem to play no role in total glucocorticoid binding they are suggested to influence the rate constant of uptake and depletion.