Ultradeformable liposome loaded with zinc phthalocyanine and [Ru(NH.NHq)(tpy)NO]3+ for photodynamic therapy by topical application

Abstract

Ultradeformable liposomes (UDLs) as a drug delivery system (DDS), prepared from the unsaturated phospholipid, dioleylphosphocholine (DOPC), and containing the non-ionic surfactant Tween 20 as edge activator, have been explored as topical vehicles for zinc phthalocyanine (ZnPc) and the nitrosyl ruthenium complex [Ru(NH.NHq)(tpy)NO]3+ (RuNO) as a photosensitizers for co-generation of 1O2 and NO as reactive species, respectively. However, in order to ensure that ZnPc was present in the UDLs in its monomeric form – essential for maximal ZnPc photophysical properties – it was necessary to replace 40 wt% of the DOPC with the saturated phospholipid, dimyristoylphosphocholine (DMPC). The resultant ZnPc and complex [Ru(NH.NHq)(tpy)NO]3+ containing UDLs were stable for at least a month when stored at 4 °C, six times more elastic/deformable than conventional liposome (c-Ls), i.e. liposome prepared using the same weight ratio of lipids but in the absence of Tween 20, and to significantly enhance the in vitro permeation of ZnPc across fresh pig ear skin. The UDLs DDS incorporating ZnPc and [Ru(NH.NHq)(tpy)NO]3+ were toxic (by the MTT assay) towards B16-F10 melanoma cells when irradiated with visible light at 670 nm, the maximum absorption of ZnPc, and at a dose of 3.18 J/cm2, but not when applied in the absence of light as expected. Based on these results it is proposed that the novel topical UDLs formulation developed is a suitable delivery vehicle for photodynamic therapy.