Preliminary results of combining low frequency low intensity ultrasound and liposomal drug delivery to treat tumors in rats.

Ultrasound is a convenient trigger for site-specific drug delivery in cancer therapy. Nano-sized liposomes formulated from soy phosphatidyl choline, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] and alpha-tocopherol were loaded with Doxorubicin (Dox) using a pH gradient. The liposomal suspension was infused through the tail vein of BDIX rats possessing bilateral intradermal DHD/K12 tumors on their hind legs. Then 20-kHz ultrasound was applied to only one of the tumors for 15 minutes. This therapy was repeated weekly for 4 weeks. The results showed that in five of six rats, the tumors regressed to non-measurable size within 4 weeks. A paired comparison of the normalized size of the insonated and non-insonated tumors in the same rat indicated that the insonated tumors were smaller (p < 0.0001, n = 6 rats, 21 pairs). This observation has significant potential for non-invasive site-specific therapy of solid tumors.

The production of extracellular mucilaginous material (ECMM) in two wood-rotting basidiomycetes is affected by growth conditions.

The ability of two wood-decay basidiomycetes to produce extracellular mucilaginous material (ECMM) and its relationship with total biomass production has been investigated. Growth and ECMM production by the white-rot fungus Coriolus versicolor and the brown-rot fungus Gloeophyllum trabeum were assessed in liquid culture under different nutritional and environmental conditions. Nutritional, pH and temperature factors all influenced significantly the proportion of ECMM in the total biomass produced. When total biomass production was reduced due to unfavorable growth conditions (stress), the proportion of ECMM in the biomass was elevated. The results are discussed with regard to the possible role(s) of ECMM in the responses of these fungi to stress.

Degradation kinetics of stabilized Pluronic micelles under the action of ultrasound.

The majority of research in the area of acoustically-activated drug delivery from stabilized micelles has been focused on the rapid release of chemotherapy drugs from the core of such nano-carriers. Previous publications have shown that low-frequency ultrasound is able to release approximately 2% of Doxorubicin (Dox) from the core of Pluronic P105 micelles stabilized using a cross-linked network of N,N-diethylacrylamide (NanoDeliv) within 2 s of applying 70-kHz ultrasound. Here we use a custom-made ultrasound exposure chamber with fluorescence detection to measure the long-term fluorescence emissions of Dox from the NanoDeliv after 2 h of exposure to two ultrasound frequencies, 70 and 476 kHz, at a mechanical index of 0.9. Fluorescence measurements are then used to deduce the degradation kinetics of stabilized Pluronic micelles during 24 h following exposure to ultrasound. Results show that ultrasound does disrupt the covalent network of the stabilized micelles, but the time constant of network degradation is very long compared to the time constant pertaining to drug release from micelles. Experiments also show no significant difference in degradation rates when employing the two frequencies in question at the same mechanical index.

Fungicides affect the production of extracellular mucilaginous material (ECMM) and the peripheral growth unit (PGU) in two wood-rotting basidiomycetes.

This study shows the effect of two fungicides on the production of extracellular mucilaginous material (ECMM) in two wood-rotting basidiomycetes and identifies a mechanism that might be responsible for the variation observed. Increasing concentrations of the fungicides copper sulphate (CuSO4) and cyproconazole in the growth medium increased the proportion of ECMM in the biomass of Trametes versicolor and Gloeophyllum trabeum. These fungicides also caused a reduction in the length of the peripheral growth unit (PGU) of the mycelia leading to a more highly branched morphology and a larger number of hyphal tips, the sites for active secretion of ECMM, per unit length of mycelium. It is postulated that both in T. versicolor and G. trabeum this change in growth leads to the increases observed in the proportion of ECMM in the total biomass. The implications of these results are discussed with a view to a potential protective role of ECMM against stress and toxic environments.