Optimization of protoporphyrin IX skin delivery for topical photodynamic therapy: Nanodispersions of liquid-crystalline phase as nanocarriers.

Abstract Nanodispersions of liquid-crystalline phases (NLPs) composed of monoolein and oleic acid were chosen as nanocarriers to improve the topical retention of the photosensitizer protoporphyrin IX (PpIX) and thereby optimize photodynamic therapy (PDT) using this photosensitizer. The nanodispersions were characterized by polarized light microscopy, small-angle X-ray diffraction and dynamic light scattering. The stability and encapsulation efficiency (EE%) of the nanodispersions were also evaluated. In vitro and in vivo skin penetration studies were performed to determine the potential of the nanodispersions for cutaneous application. In addition, skin penetration and skin irritancy (in an animal model) after in vivo application were visualized by fluorescence light microscopy. The nanodispersion obtained was characterized as a monodisperse system (~ 150.0 nm) of hexagonal liquid-crystalline phase, which provided a high encapsulation efficiency of PpIX (~ 88%) that remained stable over 90 days of investigation. Skin penetration studies demonstrated that the nanodispersion enhanced PpIX skin uptake 11.8- and 3.3-fold ( in vitro ) and 23.6- and 20.8-fold ( in vivo ) compared to the PpIX skin uptake of control formulations, respectively. In addition, the hexagonal phase nanodispersion did not cause skin irritation after application for two consecutive days. Overall, the results show that the nanocarrier developed is suitable for use in topical PDT with PpIX.