Studies on the development and characterization of sonosensitive organic nanoparticles for an ultrasound controlled, local release of pharmaceutical agents

点击翻译按钮获取中文摘要

Nanoparticles are of great interest as carriers for pharmaceutical active ingredients for a time and spatial controlled release in certain target areas as so-called "drug delivery". An important area of application is localized chemotherapy of tumor diseases which prevents the entire body from being exposed to the therapeutic agent and thus reduces otherwise unpleasant and harmful side effects. Because of their small size, the individual nanoparticles favor the advantage of the EPR effect (enhanced permeability and retention) over the substantially larger carriers in the form of microparticles. This allows for a stronger penetration of the active ingredient into and a stronger action on the tumor tissue.Our project focuses on "sonosensitive" nanostructures in which the active substances can be released by ultrasound exposition. In order to limit this effect to specific tumor regions, focused ultrasonic wave fields are required. Until now, the desired effect on sonosensitive nanoparticles of suitable size was detectable only at low ultrasonic frequencies which do not permit sufficient focusing. However, recently the applicants have succeeded in the realization of new sonosensitive nanoparticles (in the form of spheres and capsules) in which the effect also occurs at higher ultrasonic frequencies with well-focused wave fields. The newly developed nanoparticles represent rehydrated, freeze - dried poly(lactic acid) nanospheres in a water dispersion, with a diameter of 120 nm. Broadband noise is generated by sonication at 835 kHz, which is due to transient, active ingredients - releasing cavitation.In the planned project, nanoparticle production is to be optimized with a view to efficient release of active ingredients. The mechanism by which ultrasound causes inertial cavitation of these nanostructures will be determined. Microscopic methods (light microscopy, electron microscopy, scanning force microscopy) will be used for the morphological characterization of the particles. For the functional characterization of the effectiveness of the particles, an actuator sensor system has to be implemented, which on the actuator side has a unit for generating focused power ultrasound, which allows optimization of the cavitation process by variation of relevant ultrasonic operation parameters. Various ultrasonic methods for the passive and the active detection of cavitation are to be implemented and tested on the sensor side. The sensor modalities should be used in a suitable combination for the optimization of the nanoparticle production process as well as for the efficient, cavitation-based release of active ingredients. Based on the results and findings gained in the project, concept proposals and systematic approaches for the application in medicine are to be developed.