Cancer clinical research using heat-generating nanoparticles named magnetite cationic liposomes (MCL) and alternating magnetic field (AMF) irradiator has been conducted. Heat generation from intratumorally injected MCL particles was triggered by AMF irradiation to kill cancer cells nearby located. Tumor temperature was monitored as index to control treatment condition but efficacy was variable from complete regression to ineffective. In order to improve efficacy, we have proposed novel index of heat dose in vivo (J/cm3 tumor volume). Purpose of this study was to reveal actual heat dose in vivo and discuss its utility as index.

We have carried out Raman spectroscopic measurements on the anhydrous LnCl3 • 20MeOH solutions (Ln3+=Pr3+ and Ho3+) as a function of pressure at room temperature. Pressure dependence of the frequency of the Ln-Cl Raman band (vLn-Cl) is examined in conjunction with the formation of chloro-complexes. We have found that the vLn-Cl wavenumber decreases with increasing pressure, which means that the higher chloro-complexes become dominant species at high pressures.

In this study, we examined a relationship between hydrophilic solute and water (vehicle) transports in the excised hairless rat skin in the presence of ultrasound (41 kHz, 60-300 mW/cm2) irradiation and also conducted skin surface observation using confocal microscopy. When the applied intensity was increased stepwise over the rage of 60-300 mW/cm2, the transport of tritiated water (3H2O) was increased 140-fold in an intensity-dependent manner and this returned to normal on stopping the ultrasound application. The skin permeation clearance (mul/h) of model hydrophilic solutes, calcein (MW 623) and FITC-labeled dextrans [MW 4400 (FD-4) and MW 38000 (FD-40)], across the skin under the influence of ultrasound was plotted against the corresponding 3H2O flux (microl/h) to estimate the potential contribution of convective solvent flow, induced by the ultrasound application, to the solute transport. Good correlations were observed between the 3H2O flux and solute clearances and, unexpectedly, the slope values obtained from linear regression of the plots were consistent for all solutes examined (1.04+/-0.29 for calcein, 1.07+/-0.17 for FD-4, and 1.08+/-0.23 for FD-40, respectively). Transport of intact FD-4 and FD-40 was confirmed by gel permeation chromatography. When the skin surface and deeper regions of the skin after sonophoresis of FD-40 were observed using a confocal microscope, the fluorescence of FD-40 was uniformly distributed in the area under the ultrasound horn and also evident in crack-like structures in the boundary of the horn. On the other hand, a hexagonal structure of horny cells in the stratum corneum (SC) observed by post-staining with rhodamine B was fully conserved in the area under the horn. These findings suggest that 41 kHz ultrasound can increase the transdermal transport of hydrophilic solutes by inducing convective solvent flow probably via both corneocytes and SC lipids as well as newly developed routes. Our observation also suggests that 41 kHz (low-frequency) ultrasound has the potential to deliver hydrophilic large molecules transdermally.

Sonophoretic drug transport with low-frequency (41-445 kHz) and low-intensity (60-240 mW/cm2) ultrasound was characterized using hydrophilic calcein and deuterium oxide (D2O) as a solvent vehicle in excised hairless rat skin. The excised skin was mounted in vertical diffusion chambers for measurement of skin resistance and sonophoretic transport of calcein and D2O. The calcein content of the skin was also measured after ultrasound application. When the stratum corneum (sc) side was exposed to ultrasound at an intensity of 60 mW/cm2 for 30 min, the calcein flux in the sc-to-dermis direction was increased by 22.3-, 6.3-, and 3.8-fold from a baseline of 0.0088+/-0.0100 nmol/(cm2 x h) at frequencies of 41, 158, and 445 kHz, respectively, without significant changes in skin resistance. The ultrasonically-enhanced fluxes returned to baseline following cessation of the ultrasound application. At 41 kHz, there was a further increase in the magnitude of enhancement and a significant decrease in skin resistance (by 50% of the baseline resistance) on increasing the intensity from 60 to 120 mW/cm2, whereas no further enhancement was observed at 158 and 445 kHz up to 240 mW/cm2. Comparison of the calcein content in the skin before, during, and after ultrasound application at 41 kHz, 120 mW/cm2, was consistent with a transient ultrasonically-induced increase in calcein flux. In the sonophoretic transport experiments at 41 kHz, 120 mW/cm2, calcein transport correlated well with D2O transport. When 41-kHz ultrasound was applied to the sc side at 120 mW/cm2, the calcein and D2O fluxes in the sc-to-dermis direction were 13.7- and 5.2-fold higher than those in the dermis-to-sc direction. Similar directionality was also observed in tape-stripped skin, suggesting possible induction of convection in the direction of sound propagation. However, dermal application under the same ultrasound conditions induced neither an increase in calcein and D2O transport nor a decrease in skin resistance. These results demonstrate that low frequency sonophoresis is a potentially useful technique for controlling transdermal drug transport. Convective solvent flow as well as structural alteration of the skin induced by ultrasound are likely to be responsible for the observed sonophoretic transport enhancement.