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