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

Beyond Paradigms in Cultural Astronomy. Proceedings of the 27th SEAC conference held together with the EAA

Proceedings of the 27th SEAC conference held together with the EAA.-- Editors: A. César González-García, Roslyn M. Frank, Lionel D. Sims, Michael A. Rappenglück, Georg Zotti, Juan A. Belmonte, Ivan Šprajc.Cultural Astronomy is the endeavour to understand the role of the sky in past and present societies, and how these societies incorporated the sky into their culture. This broad ranging discipline is closely related to archaeology when investigating material remains of the past. Cultural Astronomy also explores the role of the heavens from the perspectives of the anthropological sciences. In recent decades the discipline has been concerned with methodological and theoretical issues. This volume offers chapters based on presentations at the 27th SEAC meeting held in Bern (2019). These chapters provide a vivid image of front-line research in diverse areas, from Roman light and shadow effects to highlight power, to Maya city organization, Etruscan temple orientation or the ontology of the sky.Peer reviewe

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

Investigation of the Inertial Cavitation Activity of Sonosensitive and Biocompatible Nanoparticles for Drug Delivery Applications Employing High Intensity Focused Ultrasound

An approach to improve chemotherapy, while minimizing side effects, is a local drug release close to the tumorous tissue. For this purpose, the active drug component is often bound to nanoparticles employed as drug carriers. In the present study, we investigate sonosensitive, biocompatible poly-(L)-lactic acid (PLA) nanoparticles, which shall be used as drug carriers. For drug release, High Intensity Focused Ultrasound (HIFU) will be employed to introduce inertial cavitation, which separates the active drug component from the drug carrier. The cavitation effect generates an acoustic noise signal, which characterizes the cavitation activity and is expected to serve simultaneously as an indicator for the release of the active drug component. Depending on the ultrasound frequency, different acoustic levels of the inertial cavitation activity were measured. Investigations using a setup for passive cavitation detection (PCD) deliver quantitative results regarding the frequency dependence of the cavitation activity level of nanoparticles and reference media

Determination of the Cavitation Pressure Threshold in Focused Ultrasound Wave Fields applied to Sonosensitive, Biocompatible Nanoparticles for Drug Delivery Applications

Employing sonosensitive nanoparticles as carriers of active pharmaceutical ingredients emerges in ultrasonic Drug Delivery. Drug release can be initiated by focused ultrasound via the effect of inertial cavitation in certain target areas of particle loaded tissue. For stimulating inertial cavitation, a specific peak rarefaction pressure threshold must be exceeded. This pressure threshold has to be determined in order to estimate the risk of tissue damage during the drug release procedure. Therefore, this study provides a method to reliably verify the cavitation pressure threshold of sonosensitive and biocompatible nanoparticles