Third party funded individual grant
Acronym: DFG 899/6-2
Start date : 01.09.2022
End date : 31.08.2025
Nanoparticles as carriers of pharmaceutical agents that can be released at specific times and in specific target areas in the sense of so-called “drug delivery” are of great interest to medicine. An important area of application is localized chemotherapy for tumor diseases, which prevents the entire body from being exposed to the therapeutic agent, thereby reducing otherwise harmful side effects. Due to their small size, individual nanoparticles have an advantage over larger drug carriers in the form of microparticles in that they can utilize the EPR effect (enhanced permeability and retention). This allows the drug to penetrate more deeply into tumor tissue and have a stronger effect on it. Our project focuses on “sonosensitive” nanostructures in which the active substances can be released by the action of ultrasound. Focusable ultrasound fields are required to limit this effect to specific tumor regions. Until now, the desired effect on sonosensitive nanoparticles of a suitable size has only been detectable at low ultrasound frequencies, which do not allow sufficient focusing. However, the applicants have recently succeeded in developing new sonosensitive nanoparticles (in the form of spheres and capsules) in which the effect also occurs at higher ultrasound frequencies with well-focused wave fields. The new nanoparticles are rehydrated, freeze-dried polylactic acid nanospheres in a water dispersion with a diameter of 120 nm, on which broadband noise is generated by sonication at 835 kHz, which is attributable to transient, drug-releasing cavitation. The planned project aims to optimize nanoparticle production with regard to efficient drug release. The mechanism of ultrasound-induced cavitation of such nanostructures will be elucidated. Microscopic methods (e.g., atomic force microscopy) will be used for the morphological characterization of the particles. For the functional characterization of the particles' effectiveness, an actuator-sensor system will be implemented that has a unit on the actuator side for generating focused power ultrasound, which allows the cavitation process to be optimized by varying relevant ultrasound parameters. On the sensor side, various ultrasonic methods for passive and active detection of cavitation will be implemented and tested. The sensor modalities are to be used in a suitable combination to optimize nanoparticle production and the operating mode for efficient, cavitation-based drug release. Based on the findings obtained in the project, concept proposals and system designs for medical applications are to be developed.
Nanoparticles as carriers of pharmaceutical agents that can be released at specific times and in specific target areas in the sense of so-called “drug delivery” are of great interest to medicine. An important area of application is localized chemotherapy for tumor diseases, which prevents the entire body from being exposed to the therapeutic agent, thereby reducing otherwise harmful side effects. Due to their small size, individual nanoparticles have an advantage over larger drug carriers in the form of microparticles in that they can utilize the EPR effect (enhanced permeability and retention). This allows the drug to penetrate more deeply into tumor tissue and have a stronger effect on it. Our project focuses on “sonosensitive” nanostructures in which the active substances can be released by the action of ultrasound. Focusable ultrasound fields are required to limit this effect to specific tumor regions. Until now, the desired effect on sonosensitive nanoparticles of a suitable size has only been detectable at low ultrasound frequencies, which do not allow sufficient focusing. However, the applicants have recently succeeded in developing new sonosensitive nanoparticles (in the form of spheres and capsules) in which the effect also occurs at higher ultrasound frequencies with well-focused wave fields. The new nanoparticles are rehydrated, freeze-dried polylactic acid nanospheres in a water dispersion with a diameter of 120 nm, on which broadband noise is generated by sonication at 835 kHz, which is attributable to transient, drug-releasing cavitation. The planned project aims to optimize nanoparticle production with regard to efficient drug release. The mechanism of ultrasound-induced cavitation of such nanostructures will be elucidated. Microscopic methods (e.g., atomic force microscopy) will be used for the morphological characterization of the particles. For the functional characterization of the particles' effectiveness, an actuator-sensor system will be implemented that has a unit on the actuator side for generating focused power ultrasound, which allows the cavitation process to be optimized by varying relevant ultrasound parameters. On the sensor side, various ultrasonic methods for passive and active detection of cavitation will be implemented and tested. The sensor modalities are to be used in a suitable combination to optimize nanoparticle production and the operating mode for efficient, cavitation-based drug release. Based on the findings obtained in the project, concept proposals and system designs for medical applications are to be developed.