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

Pia-Theresa Hiltl 1 , Michael Fink 2 , Stefan J. Rupitsch 2 , Geoffrey Lee 1  and Helmut Ermert 2
  • 1 Division of Pharmaceutics, University of Erlangen, Cauerstrasse 4, 91058 Erlangen, Germany
  • 2 Division of Sensor Technology, University of Erlangen, Paul-Gordan-Strasse 3/5, 91052 Erlangen, Germany

Abstract

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.

We have produced Poly-(L)-lactic acid (PLLA) nanoparticles by a solvent evaporation technique that serve as nucleus for inertial cavitation at moderate acoustic pressure of 800 kPa and at high frequencies of 800 kHz after the particles have been freeze-dried. In this contribution, we characterize the designed particles and present the production process. Moreover, we show that these particles enable inertial cavitation at an acoustic pressure and at acoustic frequencies which are commonly used in clinical ultrasound units. We also show that other particles with the same size at the same acoustic parameters do not induce cavitation activity.

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Current Directions in Biomedical Engineering is an open access journal and closely related to the journal Biomedical Engineering - Biomedizinische Technik. CDBME is a forum for the exchange of knowledge in the fields of biomedical engineering, medical information technology and biotechnology/bioengineering for medicine and addresses engineers, natural scientists, and clinicians working in research, industry, or clinical practice.

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