Nanostructured ultra-thin patches for ultrasound-modulated delivery of anti-restenotic drug

• Main Authors: Vannozzi L, Ricotti L, Filippeschi C, Sartini S, Coviello V, Piazza V, Pingue P, La Motta C, Dario P, Menciassi A
• Format: Article
• Language: English
• Published: Dove Medical Press 2015-12-01
• Series: International Journal of Nanomedicine
• Subjects: restenosis; micro/nano therapeutic systems; thin films; layer-by-layer polyelectrolytes; barium titanate nanoparticles; drug delivery; ultrasound.
• Online Access: https://www.dovepress.com/nanostructured-ultra-thin-patches-for-ultrasound-modulated-delivery-of-peer-reviewed-article-IJN

Lorenzo Vannozzi,1 Leonardo Ricotti,1 Carlo Filippeschi,2 Stefania Sartini,3 Vito Coviello,3 Vincenzo Piazza,4 Pasqualantonio Pingue,5 Concettina La Motta,3 Paolo Dario,1 Arianna Menciassi1 1The BioRobotics Institute, Scuola Superiore Sant’Anna, 2Center for MicroBioRobotics at SSSA, Istituto Italiano di Tecnologia, Pontedera, 3Department of Pharmacy, University of Pisa, 4Center for Nanotechnology Innovation at NEST, Istituto Italiano di Tecnologia, 5NEST, Scuola Normale Superiore, Istituto Nanoscienze-CNR, Pisa, Italy Abstract: This work aims to demonstrate the possibility to fabricate ultra-thin polymeric films loaded with an anti-restenotic drug and capable of tunable drug release kinetics for the local treatment of restenosis. Vascular nanopatches are composed of a poly(lactic acid) supporting membrane (thickness: ~250 nm) on which 20 polyelectrolyte bilayers (overall thickness: ~70 nm) are alternatively deposited. The anti-restenotic drug is embedded in the middle of the polyelectrolyte structure, and released by diffusion mechanisms. Nanofilm fabrication procedure and detailed morphological characterization are reported here. Barium titanate nanoparticles (showing piezoelectric properties) are included in the polymeric support and their role is investigated in terms of influence on nanofilm morphology, drug release kinetics, and cell response. Results show an efficient drug release from the polyelectrolyte structure in phosphate-buffered saline, and a clear antiproliferative effect on human smooth muscle cells, which are responsible for restenosis. In addition, preliminary evidences of ultrasound-mediated modulation of drug release kinetics are reported, thus evaluating the influence of barium titanate nanoparticles on the release mechanism. Such data were integrated with quantitative piezoelectric and thermal measurements. These results open new avenues for a fine control of local therapies based on smart responsive materials. Keywords: restenosis, micro/nanotherapeutic systems, thin films, layer-by-layer polyelectrolytes, barium titanate nanoparticles, drug delivery, ultrasound