Using laser microporation to improve transdermal delivery of diclofenac: Increasing bioavailability and the range of therapeutic applications

The objective of the study was to investigate the effect of laser microporation, using P.L.E.A.S.E.(R) technology, on diclofenac delivery kinetics. Skin transport of diclofenac was studied from aqueous solution, propylene glycol and marketed formulations across intact and laser-porated porcine and human skins; cumulative permeation and skin deposition were quantified by HPLC. After 24 h, cumulative diclofenac permeation across skins with 150, 300, 450 and 900 shallow pores (50-80 mu m) was 3.7-, 7.5-, 9.2- and 13-fold superior to that across untreated skin. It was also found to be linearly dependent on laser fluence; Permeation (mu g/cm(2))= 11.35 (*) Fluence (J/cm(2)) + 352.3; r(2) = 0.99. After 24 h, permeation was 539.6 +/- 78.1, 934.5 +/- 451.5, 1451.9 +/- 151.3 and 1858.6 +/- 308.5 mu g/cm(2), at 22.65, 45.3, 90.6 and 135.9 J/cm(2), respectively. However, there was no statistically significant effect of laser fluence on skin deposition. Diclofenac delivery from marketed gel formulations was also significantly higher across laser-porated skins (e.g. for Solaraze (TM), cumulative permeation after 24 h across treated (900 pores/135.9 J/cm(2)) and untreated skin was 974.9 +/- 368.8 and 8.2 +/- 3.8 mu g/cm(2), respectively. Diclofenac delivery from Solarazen (TM) across laser-porated porcine and human skins was also shown to be statistically equivalent. The results demonstrated that laser microporation significantly increased diclofenac transport from both simple and semi-solid formulations through porcine and human skin and that pore depth and pore number could modulate delivery kinetics. A similar improvement in topical diclofenac delivery in vivo may increase the number of potential therapeutic applications. (C) 2011 Elsevier B.V. All rights reserved.