Development of different temoporfin-loaded invasomes-novel nanocarriers of temoporfin: Characterization, stability and in vitro skin penetration studies

A previous study revealed that the invasome dispersion containing 3.3% (w/v) ethanol and 1% (w/v) of the terpene mixture (cineole:citral:d-limonene = 45:45: 10, v/v = standard mixture) could significantly enhance skin penetration of the highly hydrophobic photosensitizer temoporfin (mTHPC). Invasomes enhanced mTHPC-deposition in stratum corneum (SC) compared to liposomes without terpenes and conventional liposomes, and they were efficient in delivering mTHPC to deeper skin layers [J. Control. Release 127 (2008) 271-280]. The aim of this study was to develop new mTHPC-loaded invasomes in order to further enhance the drug penetration. The ratio between cl-limonene, citral and cineole was varied in the standard terpene mixture and also single terpenes were used. As a result new mTHPC-loaded invasome dispersions were prepared, characterized and investigated for stability and in vitro penetration of mTHPC into abdominal human skin using Franz diffusion cells. Invasomes were of a small particle size (<150 nm), high homogeneity (<0.3), mostly unilamellar and spherical, but also deformed vesicles were detected. Invasomes containing 1% (w/v) cineole provided the highest skin penetration enhancement of mTHPC, i.e. they provided high amounts of mTHPC in the SC and deeper skin layers, indicating that also incorporation of a single terpene into invasomes could provide efficient nanocarriers of mTHPC. These invasomes could be considered as a promising tool for delivering the photosensitizer mTHPC to the skin. However, in contrast to most invasomes, being effective nanocarriers of mTHPC, there were also formulations less effective than liposomes containing 3.3% (w/v) ethanol and one formulation was less efficient than conventional liposomes. (C) 2008 Elsevier B.V. All rights reserved.