Ultrasound-mediated drug delivery using liposomes modified with a thermosensitive polymer

Ultrasound-mediated drug delivery was established using liposomes that were modified with the thermosensitive polymer (TSP) poly(NIPMAM-co-NIPAM), which sensitized the liposomes to high temperatures. TSP-modified liposomes (TSP liposomes) released encapsulated calcein under 1 MHz ultrasound irradiation at 0.5 W/cm² for 120 s as well as the case under incubation at 42 °C for 15 min. In addition, uptake of the drug released from TSP liposomes by cancer cells was enhanced by ultrasound irradiation. In a cell injury assay using doxorubicin (DOX)-loaded TSP liposomes and ultrasound irradiation, cell viability of HepG2 cells at 6 h after ultrasound irradiation (1 MHz, 0.5 W/cm² for 30 s) with DOX-loaded TSP liposomes (TSP/lipid ratio = 1) was 60%, which was significantly lower than that of the control conditions such as DOX-loaded TSP liposomes alone and DOX-loaded intact liposomes under ultrasound irradiation.     

Sonochemical and high-speed optical characterization of cavitation generated by an ultrasonically oscillating dental file in root canal models

Ultrasonically Activated Irrigation makes use of an ultrasonically oscillating file in order to improve the cleaning of the root canal during a root canal treatment. Cavitation has been associated with these oscillating files, but the nature and characteristics of the cavitating bubbles were not yet fully elucidated. Using sensitive equipment, the sonoluminescence (SL) and sonochemiluminescence (SCL) around these files have been measured in this study, showing that cavitation occurs even at very low power settings. Luminol photography and high-speed visualizations provided information on the spatial and temporal distribution of the cavitation bubbles. A large bubble cloud was observed at the tip of the files, but this was found not to contribute to SCL. Rather, smaller, individual bubbles observed at antinodes of the oscillating file with a smaller amplitude were leading to SCL. Confinements of the size of bovine and human root canals increased the amount of SL and SCL. The root canal models also showed the occurrence of air entrainment, resulting in the generation of stable bubbles, and of droplets, near the air–liquid interface and leading eventually to a loss of the liquid.     

Targeted and ultrasound-triggered drug delivery using liposomes co-modified with cancer cell-targeting aptamers and a thermosensitive polymer

In this study, we demonstrated the feasibility of targeted and ultrasound-triggered drug delivery using liposomes co-modified with single stranded DNA aptamers that recognized platelet-derived growth factor receptors (PDGFRs) as targeting ligands for breast cancer cells and poly(NIPMAM-co-NIPAM) as the thermosensitive polymer (TSP) to sensitize these liposomes to high temperature. TSP-modified liposomes (TSP liposomes) released encapsulated calcein under 1 MHz ultrasound irradiation for 30 s at 0.5 W/cm² as well as the case under incubation for 5 min at 42 °C. Ultrasound-triggered calcein release from TSP liposomes was due to an increased local temperature, resulting from cavitation bubble collapse induced by ultrasound, and not due to an increase in the bulk medium temperature. Liposomes modified with PDGFR aptamers (APT liposomes) bound to MDA-MB-231 human breast cancer cells through PDGFR aptamers; however, they did not bind to primary human mammary epithelial cells (HMECs). The binding of APT liposomes was greatest for MDA-MB-231 cells, followed by MCF-7, WiDr, and HepG2 cancer cells. In a cell injury assay using doxorubicin (DOX)-loaded APT/TSP liposomes and ultrasound irradiation, cell viability of MDA-MB-231 at 24 h after ultrasound irradiation (1 MHz for 30 s at 0.5 W/cm²) with DOX-loaded APT/TSP liposomes was 60%, which was lower than that with ultrasound irradiation and DOX-loaded TSP liposomes or with DOX-loaded APT/TSP liposomes alone.     

Ultrasonic cavitation erosion of gas nitrided Ti–6Al–4V alloys

Ultrasonic cavitation erosion experiments were performed on Ti–6Al–4V alloys samples in annealed, nitrided and nitrided and subsequently heat treated state. The protective oxide layer formed as a result of annealing and heat treatment after nitriding is eliminated after less than 30 min cavitation time, while the nitride layer lasts up to 90 min cavitation time. Once the protective layer is removed, the cavitation process develops by grain boundary erosion, leading to the expulsion of grains from the surface. The gas nitrided Ti–6Al–4V alloy, forming a Ti_xN surface layer, proved to be a better solution to improve the cavitation erosion resistance, compared to the annealed and nitrided and heat treated state, respectively. The analysis of the mean depth of erosion rate at 165 min cavitation time showed an improvement of the cavitation erosion resistance of the nitrided samples of up to 77% higher compared to the one of the annealed samples.     

Ultrasound line-by-line scanning method of spatial–temporal active cavitation mapping for high-intensity focused ultrasound

This paper presented an ultrasound line-by-line scanning method of spatial–temporal active cavitation mapping applicable in a liquid or liquid filled tissue cavities exposed by high-intensity focused ultrasound (HIFU). Scattered signals from cavitation bubbles were obtained in a scan line immediately after one HIFU exposure, and then there was a waiting time of 2 s long enough to make the liquid back to the original state. As this pattern extended, an image was built up by sequentially measuring a series of such lines. The acquisition of the beamformed radiofrequency (RF) signals for a scan line was synchronized with HIFU exposure. The duration of HIFU exposure, as well as the delay of the interrogating pulse relative to the moment while HIFU was turned off, could vary from microseconds to seconds. The feasibility of this method was demonstrated in tap-water and a tap-water filled cavity in the tissue-mimicking gelatin–agar phantom as capable of observing temporal evolutions of cavitation bubble cloud with temporal resolution of several microseconds, lateral and axial resolution of 0.50 mm and 0.29 mm respectively. The dissolution process of cavitation bubble cloud and spatial distribution affected by cavitation previously generated were also investigated. Although the application is limited by the requirement for a gassy fluid (e.g. tap water, etc.) that allows replenishment of nuclei between HIFU exposures, the technique may be a useful tool in spatial–temporal cavitation mapping for HIFU with high precision and resolution, providing a reference for clinical therapy.     

Sonophoresis in transdermal drug deliverys

Transdermal drug delivery (TDD) has several significant advantages compared to oral drug delivery, including elimination of pain and sustained drug release. However, the use of TDD is limited by low skin permeability due to the stratum corneum (SC), the outermost layer of the skin. Sonophoresis is a technique that temporarily increases skin permeability such that various medications can be delivered noninvasively. For the past several decades, various studies of sonophoresis in TDD have been performed focusing on parameter optimization, delivery mechanism, transport pathway, or delivery of several drug categories including hydrophilic and high molecular weight compounds. Based on these various studies, several possible mechanisms of sonophoresis have been suggested. For example, cavitation is believed to be the predominant mechanism responsible for drug delivery in sonophoresis. This review presents details of various studies on sonophoresis including the latest trends, delivery of various therapeutic drugs, sonophoresis pathways and mechanisms, and outlook of future studies.     

Vibration characteristics of aluminum surface subjected to ultrasonic waves and their effect on wetting behavior of solder droplets

The vibration characteristics of an aluminum surface subjected to ultrasonic waves were investigated with a combination of numerical simulation and experimental testing. The wetting behavior of solder droplets on the vibrating aluminum surface was also examined. The results show that the vibration pattern of the aluminum surface is inhomogeneous. The amplitude of the aluminum surface exceeds the excitation amplitude in some zones, while the amplitude decreases nearly to zero in other zones. The distribution of the zero-amplitude zones is much less dependent on the strength of the vibration than on the location of the vibration source. The surface of the liquid solder vibrates at an ultrasonic frequency that is higher than the vibration source, and the amplitude of the liquid solder is almost twice that of the aluminum surface. The vibration of the surface of the base metal (liquid solder) correlates with the oxide film removal effect. Significant removal of the oxide film can be achieved within 2 s when the amplitude of the aluminum surface is higher than 5.4 μm or when the amplitude of the liquid solder surface is higher than 10.2 μm.     

High-speed visualization and PIV measurements of cavitating flows around a semi-circular leading-edge flat plate and NACA0015 hydrofoil

Cavitating flows around a flat plate with semi-circular leading edge and a NACA0015 hydrofoil at attack angles ranging from 0° to 9° and with varying cavitation number are investigated using high-speed-imaging visualization (HIV) and particle-imaging velocimetry (PIV). Several known types of cavitation common to both foils, but also some different patterns, were observed. At small angles of incidence (less than 3°), cavitation on the plate begins in the form of a streak array (bubble-band) whereas on the hydrofoil as traveling bubbles. For the regimes with developed cavitation on the NACA0015 hydrofoil, the scattered and discontinuous bubble streaks branch and grow but subsequently merge into bubble clouds forming a remarkably regular lattice pattern. Once the incidence angle increased to 9°, the cavitation on the hydrofoil changed to a streaky pattern like that on the plate at small attack angles, whereas the regime on the plate showed no significant changes. The PIV method proved to be usable for measuring the instantaneous velocity also in the gas–vapor phase, albeit with reduced accuracy that was evaluated and accounted for on the basis of the effective (validation-surviving) number of imaging samples. The time-averaged velocity and turbulence moments show that the incipience of cavitation is governed by the development of the carrier-fluid flow around the foil leading edges, but the subsequent flow pattern depends strongly on the cavitation regime displaying markedly different distributions compared to the non-cavitating case. The main cavitation parameters: the maximum cavity length, the cloud cavity streamwise dimensions and the cloud shedding Strouhal number are analyzed and presented in function of the cavitation number and the attack angle in different scaling. The measurements confirm qualitatively the trends reported in the literature, but show also some quantitative differences, notably between the two foils considered.     

Effect of system parameters on the size distributions of hollow nickel microspheres produced by an ultrasound-aided electrical discharge machining process

Ultrasound-aided electric discharge machining（EDM） is an emerging technology for producing hollow nickel microspheres.This technology combines traditional EDM with the cavitation and vibration effects of ultrasound to produce hollow microspheres.In this paper,ultrasound-aided EDM was carried out in a kerosene medium（the working solution）.The effects of various parameters on the sizes of microspheres were investigated using scanning electronic microscopy（SEM）.Smileview software was used to measure the sizes of the microspheres.Originpro software was used for statistical analysis to determine the size distributions of the microspheres.To study the effects of the system parameters on the sizes of the microspheres,we first investigated the necessity of using an ultrasonic wave with EDM.After comparing the experimental results with and without the ultrasonic field,we found that ultrasound-induced cavitation and vibration effects reduced the diameters of the microspheres.We then studied the effects of several electrical parameters,including the arc current,pulse width,and gap voltage,on the sizes of the microspheres at an ultrasound frequency of 40 kHz.Smaller microspheres could be obtained by lowering the arc current,pulse width,and gap voltage.     

Shock-induced collapse of a cylindrical air cavity in water: a Free-Lagrange simulation

A Free-Lagrange CFD code is used to simulate the collapse of a cylindrical air cavity in water by a 1.9 GPa incident shock. The Lagrangian treatment allows the air/water interface to be tracked throughout the interaction. The incident shock is partially transmitted into the cavity, within which it experiences multiple reflections. The upstream cavity wall involutes to form a high-speed jet which, on impact with the far cavity wall, produces an intense blast wave. Heating of the gas within the cavity is highly non-isentropic, and is dominated by shock heating. The predicted final gas temperature is of order 12000 K, although the modelling assumptions used here lead to over-prediction of temperature during the later stages of collapse. Received 14 September 1999 / Accepted 28 June 2000