title: Nanostructured ultra-thin patches for ultrasound-modulated delivery of anti-restenotic drug.
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.
authors.affiliation: The BioRobotics Institute, Scuola Superiore Sant'Anna, Pontedera, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Vannozzi
authors.affiliation: The BioRobotics Institute, Scuola Superiore Sant'Anna, Pontedera, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Ricotti
authors.affiliation: Center for MicroBioRobotics at SSSA, Istituto Italiano di Tecnologia, Pontedera, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Filippeschi
authors.affiliation: Department of Pharmacy, University of Pisa, Pisa, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Sartini
authors.affiliation: Department of Pharmacy, University of Pisa, Pisa, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Coviello
authors.affiliation: Center for Nanotechnology Innovation at NEST, Istituto Italiano di Tecnologia, Pisa, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Piazza
authors.affiliation: NEST, Scuola Normale Superiore, Istituto Nanoscienze-CNR, Pisa, Italy.
authors.forename: Pasqualantonio
authors.initials: P
authors.lastname: Pingue
authors.affiliation: Department of Pharmacy, University of Pisa, Pisa, Italy.
authors.forename: Concettina
authors.initials: C
authors.lastname: La Motta
authors.affiliation: The BioRobotics Institute, Scuola Superiore Sant'Anna, Pontedera, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Dario
authors.affiliation: The BioRobotics Institute, Scuola Superiore Sant'Anna, Pontedera, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Menciassi
mesh_terms: D017609:Barium Compounds / Q000737:chemistry; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000737:chemistry; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D023903:Coronary Restenosis / Q000188:drug therapy; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry; D011725:Pyridines / Q000008:administration & dosage* / Q000737:chemistry; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000737:chemistry; D014025:Titanium / Q000737:chemistry; D014465:Ultrasonics / Q000379:methods
chemical_list: D017609:Barium Compounds; D002317:Cardiovascular Agents; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D011725:Pyridines; D011744:Pyrimidinones; C024547:barium titanate(IV); D019344:Lactic Acid; C033616:poly(lactide); D014025:Titanium
keywords: barium titanate nanoparticles; drug delivery; layer-by-layer polyelectrolytes; micro/nanotherapeutic systems; restenosis; thin films; ultrasound