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

Recently, Solaraze gel (Bioglan, Herts, UK) a topical hyaluronan (HA)/dicto fenac formulation for the treatment of actinic keratosis has received regul atory approval in the US, Canada and Europe for the treatment of actinic ke ratosis. However, a mechanism of action to explain the topical delivery pro perties of HA remains to be elucidated. Thus, the aim of this study was to compare the effect of HA with other glycosaminoglycans (chondroitin sulphat e (CS), heparin (HP)) and pharmaceutically relevant polysaccharides (sodium carboxymethyl cellulose and pectin) on the dermal partitioning and percuta neous penetration of diclofenac and ibuprofen. The studies demonstrated tha t HA significantly enhanced the partitioning of both diclofenac and ibuprof en into human skin when compared to an aqueous control, pectin and carboxym ethylcellulose (P < 0.01). Although the HA vehicle increased the partitioni ng of both drugs compared to the effects of the other glycosaminoglycans, C S and HP, this difference was not significant (P > 0.05). However, the resu lts from the Franz cell diffusion studies showed that HA (1% w/w) significa ntly enhanced the amount of drug localising within the skin when compared t o 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 rig hts reserved.