THE EFFECT OF HYALURONAN ON THE IN-VITRO DEPOSITION OF DICLOFENAC WITHIN THE SKIN

Hyaluronan is a glycosaminoglycan and has a protective, shock-absorbin g and structure-stabilizing role in connective tissue. Recently, ii ha s been suggested that hyaluronan can be used as a controlled and local ized delivery vehicle for diclofenac in the treatment of a variety of conditions including osteoarthritic pain, basal cell carcinoma and act inic keratosis. The aim of this study was to examine the effects of hy aluronan on the in-vitro diffusion and deposition of diclofenac within the skin. The studies involved full thickness, epidermal sheet and st ratum corneum human shin sections in an in-vitro Franz cell model, in which the diffusion and deposition of C-14-labelled diclofenac and H-3 -labelled hyaluronan was investigated The results showed that the diff usion of C-14-labelled diclofenac was sustained and controlled by hyal uronan as compared to a buffer control, that a depot or. reserver of t he drug was formed in the epidermis and that it was probably this laye r that determined the rate of release of diclofenac within the skin. H -3-labelled hyaluronan was iouridio penetrate ail layers of the skin, although the rate of diffusion was much slower than that of labelled d iclofenac. Again,mosi of the activity was found to be retained within the epidermis, which supports the hypothesis oi the importance of this layer in the mode of action. The presence within the epidermis of pot ential receptors for hyaluronan has recently been confirmed, and this may partially explain the findings of the present in-vitro studies.