Study of pharmacokinetics of liposomal photosensitiser based on hydroxyaluminium tetra-3-phenylthiophthalocyanine on mice

Abstract

The present work is devoted to the study of pharmacokinetics of infrared photosensitizer (PS) based on hydroxyaluminium tetra‑3‑phenylthiophthalocyanine in a sterically stabilized liposomal form. The study was carried out on adult female mice. The PS was administered once intravenously at a dose of 6 mg / kg. Evaluation of the PS accumulation dynamics in the mice tissues and organs was performed at time intervals from 5 minutes to 7 days using spectral‑fluorescent method. The maximum accumulation of the PS photoactive form was recorded in lungs (32 µg / g in the interval of 5–30 minutes after introduction), liver (20.8 µg / g in the interval of 4–24 hours after introduction) and spleen (28 µg / g 4 hours after introduction). At the same time, by the end of the observation period (7 days after administration), trace amounts of the PS photoactive form were still detected in the liver and the spleen at a calculated concentration of 0.5‑1 µg / g. The PS accumulated the least in muscles and skin. The fluorescent signal from the PS accumulated in skin was detectable almost immediately, and its concentration remained at the same level (1.2‑1.5 µg / g) for up to 3 days of observation. In the muscles, the concentration of the PS reached 1.5 µg / g 15 minutes after administration, and then gradually decreased until 0.25 µg / g at 24 hours. Data on the pharmacokinetics of PS in blood, basic organs and tissues of animals were obtained, pharmacokinetic parameters were calculated. 7 days after the administration, the PS concentration in the skin and muscles was below the detection limit. The studies confrmed that PEGylation of the PS liposomal form slows down the process of its capture by reticulo‑endothelial system. It was shown that the PS circulates in blood and organs of mice for a long time and it completely distributes only when 4 hours pass after administration.