There is growing interest in integrating nanotechnology with medicine, with the aim to provide diagnosis and treatment of diseases. In this context drug delivery techniques have emerged as methods to administering a pharmaceutical compound in the site of interest. Therapeutic efficacy may be enhanced by triggering drug release in the desired organ in a controlled manner using a non-invasive external stimulus.
Starting from these considerations, the innovative idea of this project is to demonstrate the proof-of-concept of remotely control of liposomes vesicles, by means of nanosecond pulses electric signal.
Such objective will be pursued combining three steps: the design and realization of laboratory exposure systems as well as of the non-invasive applicator; the synthesis of the liposome and the exposure of the suitable liposome solution.
The state of the art regarding applicators for stimuli-responsive liposomes activated by pulsed electric fields is confined to laboratory studies where electroporation is combined to lipid nanovesicles in order to enhance transdermal delivery [Zorec, B., Zupan¿i¿, Š., Kristl, J., Pavšelj, N. Combinations of nanovesicles and physical methods for enhanced transdermal delivery of a model hydrophilic drug (2018) European Journal of Pharmaceutics and Biopharmaceutics, 127, pp. 387-397]. In this case electrodes for electric pulse delivery, arranged in a typical honeycomb configuration are used.
However, the duration of the pulses is in the order of 100 microseconds, whereas the problem of matching to the generator is not a real problem since due to the low spectral content of the signal used, a typical quasi-static configuration can be considered.
When dealing with nsPEFs (e.g. 10 ns duration) the integrity of the pulse delivered to the sample is determined by the matching of the exposure system to the generator. One example is reported in literature for testing electroporation on liposomes [Denzi, A., Valle, E.D., Esposito, G., Mir, L.M., Apollonio, F., Liberti, M. Technological and Theoretical Aspects for Testing Electroporation on Liposomes (2017) BioMed Research International, 2017, art. no. 5092704]. However, although the use of a standard electroporation cuvette has been considered advantageous it has been demonstrated the capability of such structure to deliver a 10ns pulse without a significant signal distortion only for specific conductivity value of the solution.
The design and realization of a new wideband exposure system for a proper delivery of 10 ns (or even shorter) duration pulses will represent an advancement in the research of stimuli-responsive drug delivery systems since will permit controlled and reproducible experiments of liposome vesicles exposed to nsPEFs and at the same time will open the way to the comprehension of the mechanism behind it. Moreover a challenge issue of the project will be the use of external magnetic fields, to induce, thank to the Faraday's law, electric current density and electric field suitable for electroporation of liposomes.