Otrzymywanie oraz charakterystyka liposomów - potencjalnych nośników leków w celu zwiększenia skuteczności terapii fotodynamicznej

Abstract

In context of this doctoral thesis studies was performed aiming at improving the effectiveness of photodynamic therapy by delivering tested chlorine inside the cell using liposome carriers. Main assumption of this work was preparation and characterization of liposomes as potential carriers of anticancer drugs. Before starting the preparation of phospholipid vesicles, the studies of basic physicochemical parameters of photosensitizers were conducted. In the second stage of work, designed composition of phospholipid bilayer and the obtained liposome-drug complex were characterized. Physicochemical characteristics of the tested compound dissolved in several environments were performed using various spectroscopic techniques. Different parameters such us the position of each absorption bands, the molar absorption coefficients, the positions of emission bands, the energy of singlet state, Stokes shift, the fluorescence quantum yield, fluorescence lifetime, the lifetime of excited molecules of the photosensitizer in the triplet state and the singlet oxygen quantum yield were determined. Stability of tested photosensitizer was determined during storage in a place with limited access of light. In the second part of the doctoral dissertation the basic physical parameters of six types of liposomes were defined. The research was performed for empty liposomes and liposomes with compound enclosed in the phospholipid bilayer. Using the analyzer of particle size the diameter and polydispersity index were determined. Their stability was also defined during storage at 3 °C in place with limited access of light. Experiments were also performed on cancer cells. The therapeutic efficacy of the proposed drug-liposome complex was evaluated by using the MTS assay. Examinations confirmed that test compound meets the criteria required for potential anticancer drugs. The limitation was only its aggregation in aqueous media, however this effect can be minimized by using liposomes. The results obtained from experiments performed on liposomal carriers indicate that they have adequate physical parameters and may be used to transport photosensitizers in photodynamic therapy. Main conclusion of this work is that the proposed liposome carriers can increase the efficiency of photodynamic therapy.