An in vitro investigation into the effect of glycosaminoglycans on the skin partitioning and deposition of NSAIDs

Abstract

Recently, Solaraze gel (Bioglan, Herts, UK) a topical hyaluronan (HA)/dictofenac formulation for the treatment of actinic keratosis has received regulatory approval in the US, Canada and Europe for the treatment of actinic keratosis. However, a mechanism of action to explain the topical delivery properties of HA remains to be elucidated. Thus, the aim of this study was to compare the effect of HA with other glycosaminoglycans (chondroitin sulphate (CS), heparin (HP)) and pharmaceutically relevant polysaccharides (sodium carboxymethyl cellulose and pectin) on the dermal partitioning and percutaneous penetration of diclofenac and ibuprofen. The studies demonstrated that HA significantly enhanced the partitioning of both diclofenac and ibuprofen into human skin when compared to an aqueous control, pectin and carboxymethylcellulose (P < 0.01). Although the HA vehicle increased the partitioning of both drugs compared to the effects of the other glycosaminoglycans, CS and HP, this difference was not significant (P > 0.05). However, the results from the Franz cell diffusion studies showed that HA (1% w/w) significantly enhanced the amount of drug localising within the skin when compared to all of the other polysaccharides (P < 0.05). The results suggest that the use of HA as a vehicle excipient offers potential advantages in the dermal delivery and localisation of drugs. (C) 2001 Elsevier Science B.V. All rights reserved.