Phototoxicity in vitro and safety in vivo of the emulsion photosensitizer based on furanocoumarins of Heracleum sosnowskyi.

The use of plants such as giant hogweed as raw materials for the manufacture of dosage forms has been little explored. In this study, we utilized furanocoumarins from the Heracleum sosnowskyi plant to create an experimental emulsion dosage form (EmFHS). The EmFHS was finely dispersed (481.8 nm ± 71.1 nm), shelf-stable, and contained predominantly 8-methoxypsoralen at a concentration of 1 mg/ml. Phototoxicity analysis of EmFHS for THP-1 cells under UV (365 nm) irradiation showed an IC50 of 19.1 µg/ml (24 h) and 6.3 µg/ml (48 h). In relation to spheroids (L929), EmFHS exhibited a phototoxic effect in the concentration range of 31.25-125 µg/ml8-MOP. A full phototoxic effect was observed 48 h after UV irradiation. The phototoxic effect of EmFHS in vitro was dose-dependent and comparable to the effect of emulsion synthetic 8-methoxypsoralen and chlorin e6 solution. EmFHS cytotoxicity was caused solely by UV radiation, and toxicity in the dark was minimal. EmFHS, administered at a dose of 3 mg/kg8-MOP, was found to be safe after a single intravenous administration to rats. It had a photosensitizing effect in the form of local photodermatitis when exposed to UV irradiation at a dose of 44 J/cm2. The biokinetics of emulsion furanocoumarins showed that the phototoxic effect of EmFHS is due to the high penetration ability of the emulsion into cells of spheroids. At the same time, it has a low degree of cumulation when administered intravenously. The obtained data suggest that EmFHS may be a promising treatment for PUVA therapy of various dermatological diseases. Additionally, the plant Heracleum sosnowskyi shows potential as a basis for creating new dosage forms with phototherapeutic effects.

Magnetic Hyperthermia Nanoarchitectonics via Iron Oxide Nanoparticles Stabilised by Oleic Acid: Anti-Tumour Efficiency and Safety Evaluation in Animals with Transplanted Carcinoma.

In this study, we developed iron oxide nanoparticles stabilised with oleic acid/sodium oleate that could exert therapeutic effects for curing tumours via magnetic hyperthermia. A suspension of iron oxide nanoparticles was produced and characterised. The toxicity of the synthesised composition was examined in vivo and found to be negligible. Histological examination showed a low local irritant effect and no effect on the morphology of the internal organs. The efficiency of magnetic hyperthermia for the treatment of transplanted Walker 256 carcinoma was evaluated. The tumour was infiltrated with the synthesised particles and then treated with an alternating magnetic field. The survival rate was 85% in the studied therapy group of seven animals, while in the control group (without treatment), all animals died. The physicochemical and pharmaceutical properties of the synthesised fluid and the therapeutic results, as seen in the in vivo experiments, provide insights into therapeutic hyperthermia using injected magnetite nanoparticles.

Evaluation of photocytotoxicity liposomal form of furanocoumarins Sosnowsky's hogweed.

Sosnovsky's hogweed, Heracleum sosnowskyi has a high photosensitizing ability. Although Sosnovsky's hogweed is known as a poisonous plant, its chemical composition and phototoxicity are poorly studied. We analyzed the chemical composition of the Sosnovsky's hogweed juice that grew in natural conditions. It was found that the content of 8-methoxypsoralen in the juice is 1332.7 mg/L, and that of 5-methoxypsoralen is 34.2 mg/L. We have developed and analyzed liposomes containing furanocoumarins of Sosnovsky's hogweed juice and studied their photocytotoxicity in L929 mouse fibroblast cell culture. It was found that liposomes containing furanocoumarins of Sosnovsky's hogweed juice are more toxic for L929 cells in comparison with liposomal forms of pure substances 8-methoxypsoralen and 5-methoxypsoralen. It was found that when exposed to UV radiation at 365 nm at a dose of 22.2 J/cm2, the liposomal form of furanocoumarins Sosnovsky's hogweed is 3 times more toxic to L929 cells than in the dark. It was found that the photocytotoxic effect of liposomal furanocoumarins Sosnovsky's hogweed is a strongly stimulation of apoptosis.The data obtained suggest that the raw material of Sosnovsky's hogweed claims to be a source of furanocoumarins, and the liposomal form, given the hydrophobic properties of furanocoumarins, is very suitable for creating a phototherapeutic drug.