Interactions mechanisms of temoporphin liposomal formulations with serum proteins

International audienceMeta-tetra(hydroxyphenyl)chorin (temoporfin, mTHPC) is a non-polar photosensitizer used in photodynamic therapy. To improve its solubility and pharmacokinetic properties, liposomes were proposed as drug carriers. Liposomes offer the advantage of drug monomerization and increase in photosensitizer photoactivity, as well as an enhanced permeability and retention (EPR) effect. Recently, we proposed novel liposomal formulation based on the encapsulation of inclusion complexes with mTHPC in the inner aqueous core of liposomes, namely drug-in-cyclodextrin-in-liposome (DCL). However, the stability of liposomal formulation in terms of solute release and destruction of vesicle structure presents a challenge for successful application of lipid carriers. The problem of stability was extensively studied in different in vitro and in preclinical models. The aim of the present study was to evaluate the interaction and binding specificity of mTHPC liposomal formula-tions to human serum proteins by means of gel-exclusion chromatography technique. We demonstrated the release of mTHPC from liposomal vesicles after incubation with serum. Compared with conventional liposomes DCL appeared to be more stable releasing less mTHPC to the serum proteins. The obtained data suggested that application of DCLs can be successfully applied in mTHPC-PDT. This study was supported by French “Ligue National contre le Cancer”, Belarussian Republican Foundation for Fundamental Research (grant М17МС-028) and the Ministry of Education of the Republic of Belarus. The authors thank biolitec research GmbH (Jena, Germany) for providing mTHPC