Enhanced permeation of theophylline through the skin and its effect on fibroblast proliferation

It is believed that theophylline can be helpful in psoriasis treatment by elevating cAMP levels. In the present study, theophylline skin permeation behavior from various enhancing carriers, as well as its efficacy in inhibiting psoriatic fibroblast proliferation in vitro, was studied. The results show that theophylline markedly inhibited normal and psoriatic dermal fibroblast proliferation when added to the cells at 1 mM concentration. Lower theophylline concentrations had no effect on psoriatic fibroblasts. From these results it can be assumed that a high concentration of drug needs to reach the dermis in order to be effective. The effect of oleic acid, propylene glycol and transcutol on the skin permeation fluxes of theophylline from various carrier systems (PEG base, cream, gel and ointment) was measured. The results clearly indicate that PEG base containing oleic acid and transcutol is the best enhancing carrier for theophylline (yielding a 260-times flux increase), among the systems investigated. This enhancing formulation was found to deliver to the dermis radiolabeled theophylline when applied to rat skin in vivo and visualized by autoradiography.