The effect of hyaluronan on the in vitro deposition of diclofenac within the skin.

Hyaluronan is a glycosaminoglycan and has a protective, shock-absorbing and structure-stabilizing role in connective tissue. Recently, it has been suggested that hyaluronan can be used as a controlled and localized delivery vehicle for diclofenac in the treatment of a variety of conditions including osteoarthritic pain, basal cell carcinoma and actinic keratosis. The aim of this study was to examine the effects of hyaluronan on the in-vitro diffusion and deposition of diclofenac within the skin. The studies involved full thickness, epidermal sheet and stratum corneum human skin sections in an in-vitro Franz cell model, in which the diffusion and deposition of 14C-labelled diclofenac and 3H-labelled hyaluronan was investigated. The results showed that the diffusion of 14C-labelled diclofenac was sustained and controlled by hyaluronan as compared to a buffer control, that a depot or reservoir of the drug was formed in the epidermis and that it was probably this layer that determined the rate of release of diclofenac within the skin. 3H-labelled hyaluronan was found to penetrate all layers of the skin, although the rate of diffusion was much slower than that of labelled diclofenac. Again, most of the activity was found to be retained within the epidermis, which supports the hypothesis of the importance of this layer in the mode of action. The presence within the epidermis of potential receptors for hyaluronan has recently been confirmed, and this may partially explain the findings of the present in-vitro studies.