An In Vitro Study of the Diclofenac Delivery Properties of Hyaluronan in Human Skin

Previous in vitro studies have indicated that hyaluronan, when compared to buffer controls, effects a controlled and sustained release of diclofenac through the skin by the formation of a reservoir of the drug around the basement membrane. The aim of this study was to further characterize the drug delivery properties of hyaluronan by comparing it with other gel-forming materials and another glycosaminoglycan, chondroitin sulphate. The results show that neither NaCMC (at a weight or rheologically equivalent concentration) nor chondroitin sulphate (at a weight equivalent concentration) exert the controlled release effect seen for the hyaluronan formulationin fullthickness skin. A significant difference is seen between the cumulative amounts of labelled diclofenac diffused from the controls at times where sink conditions for the hyaluronan formulation are reached (p 0.05). Mass balance calculations from each experiment show that significantly more activity is retained in the skin when applied in 2.5% HA, compared to 2.5% NaCMC (p 0.02), 3.2% NaCMC (p 0.05) and 2.5% chondroitin sulphate (p 0.02). This study supports the hypothesis that the controlled release and epidermal retention of diclofenac is a characteristic specific to the hyaluronan formulation and does not appear to be observed with another rheologically equivalent gel,such as NaCMC or an alternative glycosaminoglycan, chondroitin sulphate.