Inertial cavitation of lyophilized and rehydrated nanoparticles of poly(L-lactic acid) at 835 kHz and 1.8 MPa ultrasound

Nanoparticles of poly-L-lactic acid dispersed in water and of approximately 120 nm diameter were prepared by a nanoprecipitation method followed by lyophilization together with trehalose. After rehydration, the nanodispersion was exposed to ultrasound at 835 kHz frequency and 1.8 MPa peak negative sound pressure. Substantial levels of broadband noise were surprisingly detected which are attributed to the occurance of inertial cavitation of bubbles present in the dispersion. Inertial cavitation encompasses the formation and growth of gas cavities in the rarefaction pressure cycle which collapse in the compression cycle because of the inwardly-acting inertia of the contracting gas-liquid interface. The intensity of this inertial cavitation over 600 s was similar to that produced by Optison microbubbles used as contrast agents for diagnostic ultrasound. Non-lyophilized nanodispersions produced negligible broadband noise showing that lyophilization and rehydration are requirements for broadband activity of the nanoparticles. Photon correlation spectroscopy indicates that the nanoparticles are not highly aggregated in the nanodispersion and this is supported by scanning (SEM) and transmission (TEM) electron micrographs. TEM visualized non-spherical nanoparticles with a degree of irregular, non-smooth surfaces. Although the presence of small aggregates with inter-particulate gas pockets cannot be ruled out, the inertial cavitation activity can be explained by incomplete wetting of the nanoparticle surface during rehydration of the lyophilizate. Nano-scale gas pockets may be trapped in the surface roughness of the nanoparticles and may be released and coalesce to the size required to nucleate inertial cavitation on insonation at 835 kHz/1.8 MPa

Sonographic Detection of Iron Oxide Nanoparticles Employing Shear Waves

Research in biomedical nanotechnology led already to a variety of applications of nanoparticles in diagnosis as well as in therapy. One of these medical applications is Magnetic Drug Targeting, a promising cancer treatment technique. The aim of this medical attendance is a local chemotherapeutic treatment of the cancerous tissue. For this purpose, chemotherapeutic drugs are bound to magnetic nanoparticles and accumulated in the tumor area by means of an external static magnetic field. Hereby, a well-defined particle concentration in the cancerous tissue requires monitoring of the particle accumulation. Therefore, we present an ultrasound imaging technique that is capable of detecting quantitatively the concentration of iron oxide nanoparticles in biological tissue. The evaluation is based on the variation of the speed of sound of an induced shear wave with respect to the particle concentration

In Vivo Study on Magnetomotive Ultrasound Imaging in the Framework of Nanoparticle based Magnetic Drug Targeting

Various medical procedures make use of magnetic nanoparticles, such as Magnetic Drug Targeting (MDT), which boosts the demand for imaging modalities that are capable of in vivo visualizing this kind of particles. Magnetomotive Ultrasound is an imaging technique that can detect tissue, which is perfused by magnetic nanoparticles. In this contribution, we investigate the suitability of Magnetomotive Ultrasound to serve as a monitoring system during MDT. With the conducted measurements, it was possible for the first time to observe in vivo the accumulation of iron-oxide nanoparticles during a Magnetic Drug Targeting cancer treatment applied to a small animal (rabbit)

Quantitative Imaging of the Iron-Oxide Nanoparticle- Concentration for Magnetic Drug Targeting Employing Inverse Magnetomotive Ultrasound

Magnetomotive Ultrasound is an imaging technique that is capable to detect tissue, which is perfused by magnetic nanoparticles. However, this modality is restricted to qualitative imaging only. Therefore, we present an extended Magnetomotive Ultrasound algorithm, which allows the quantitative determination of the spatial distribution of magnetic nanoparticle density in tissue. The algorithm is based on an iterative adjustment of simulated data to measurements. Experiments with tissue-mimicking phantoms reveal that the presented method leads to the spatial particle concentration in the correct order of magnitude

Development of sonosensitive Poly-(L)-lactic acid nanoparticles

Due to serious side effects of traditional chemotherapeutic treatment, novel treatment techniques like targeted drug delivery, which allows a reduction of the overall dosage of drugs, are investigated. It is worth mentioning that at the same time, precise drug delivery offers an increased dosage of chemotherapeutic drugs in the tumorous area employing the EPR effect. Therefore, vehicles smaller than 400 nm can be used to pass the poorly aligned endothelial cells of tumour vessels passively through their fenestrations. In a subsequent step, the chemotherapeutic drugs need to be released. One possibility is an ultrasound-based release via inertial cavitation. Thereby, it is desirable to restrict the drug release to a narrow range. Thus, the cavitation inducing ultrasound wave has to be focused to that region of interest. Ultrasound frequencies of more than 500 kHz enable sufficient focusing, however, inertial cavitation occurs primarily at much lower frequencies. In order to afford inertial cavitation at 500 kHz, either bigger particles in the range of micrometres are needed as cavitation nucleus, which is not possible due to the EPR effect or high acoustic pressure is needed to generate inertial cavitation. Nevertheless, this high pressure is inappropriate for clinical applications due to thermal and mechanical effects on biological tissue