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.

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.

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.

Ultrasound-Triggerable Coatings for Foley Catheter Balloons for Local Release of Anti-Inflammatory Drugs during Bladder Neck Dilation.

Bladder neck contracture (BNC) is a complication of the surgical treatment of benign and malignant prostate conditions and is associated with the partial or complete blockage of urination. Correction of this condition usually requires repeated surgical intervention, which does not guarantee recovery. Balloon dilation is a minimally invasive alternative to the surgical dissection of tissues; however, it significantly reduces the patient's quality of life. Additional local anti-inflammatory treatment may reduce the number of procedures requested and increase the attractiveness of this therapeutic strategy. Here, we report about an ultrathin biocompatible coating based on polylactic acid for Foley catheter balloons that can provide localized release of Prednol-L in the range of 56-99 µg in the BNC zone under conventional diagnostic ultrasound exposure. Note that the exposure of a transrectal probe with a conventional gray-scale ultrasound regimen with and without shear wave elastography (SWE) was comparably effective for Prednol-L release from the coating surface of a Foley catheter balloon. This strategy does not require additional manipulations by clinicians. The trigger for the drug release is the ultrasound exposure, which is applied for visualization of the balloon's location during the dilation process. In vivo experiments demonstrated the absence of negative effects of the usage of a coated Foley catheter for balloon dilation of the bladder neck and urethra.

Enhanced cytotoxicity caused by AC magnetic field for polymer microcapsules containing packed magnetic nanoparticles.

Magnetic hyperthermia (MH) is a perspective tool to treat the tumor while the magnetic material is delivered. The key problems in MH development is to ensure an effective local heating within cancer cell without overheating other cells. In order to do that one has to reach substantial local accumulation of magnetic nanoparticles (MNPs) and/or magnetically sensitive objects with advanced heat properties. Absorbing heat energy for destroying tumor cells can be generated only if there is sufficient amount of locally placed MNPs. In this work, we propose polyelectrolyte microcapsules modified with iron oxide nanoparticles as an approach to tie magnetic materials in high concentration locally. These microcapsules (about 3 microns in diameter) can be readily internalized by various cells. The human fibroblasts uptake of the microcapsules and cytotoxic effect upon the influence of alternating magnetic field (AMF) while magnetic capsules are inside the cells is under study in this work. The cytotoxicity of the magnetic microcapsules was compared with the cytotoxicity of the MNPs while free in the solution to evaluate the effect of bounding MNPs. A cytotoxic effect on cells was found in the case of preliminary incubation of fibroblasts with capsules while the AMF is applied. In the case of MNPs in an equivalent dose per mass of magnetic material, there was no cytotoxic effect noticed after the treatment with the field. It is noteworthy that during the treatment of cells with the AMF, the increase in temperature of the incubation medium was not registered. The morphological changes on fibroblasts were consistent with the data of the viability assessment. Thus, the synthesized capsules are shown as a means for local enhancement of magnetic hyperthermia in the treatment of tumor diseases.

Submicron-Sized Nanocomposite Magnetic-Sensitive Carriers: Controllable Organ Distribution and Biological Effects.

Although new drug delivery systems have been intensely developed in the past decade, no significant increase in the efficiency of drug delivery by nanostructure carriers has been achieved. The reasons are the lack of information about acute toxicity, the influence of the submicron size of the carrier and difficulties with the study of biodistribution in vivo. Here we propose, for the first time in vivo, new nanocomposite submicron carriers made of bovine serum albumin (BSA) and tannic acid (TA) and containing magnetite nanoparticles with sufficient content for navigation in a magnetic field gradient on mice. We examined the efficacy of these submicron carriers as a delivery vehicle in combination with magnetite nanoparticles which were systemically administered intravenously. In addition, the systemic toxicity of this carrier for intravenous administration was explicitly studied. The results showed that (BSA/TA) carriers in the given doses were hemocompatible and didn't cause any adverse effect on the respiratory system, kidney or liver functions. A combination of gradient-magnetic-field controllable biodistribution of submicron carriers with fluorescence tomography/MRI imaging in vivo provides a new opportunity to improve drug delivery efficiency.