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.

Argon plasma improves the tissue integration and angiogenesis of subcutaneous implants by modifying surface chemistry and topography

“…With the recent advancements in nanotechnology, nanocomposites offer substrates with a dimension that mimics the native ECM, improving their biocompatibility. [4][5][6][7][8] Our group is currently developing a subcutaneous implant using a nanocomposite polyurethane. 4,5 This polyurethane polymer has been extensively tested and meets international standards (ISO 10993) for biocompatibility.…”

Polymeric Microporous Nanofilms as Smart Platforms for <italic>in Vitro</italic> Assessment of Nanoparticle Translocation and Caco-2 Cell Culture

“…In some studies, nanofilm flexibility has been claimed as a feature allowing them to be cyclically aspirated and ejected through pipettes or syringes. Indeed, this would enable the collection and subsequent injection of drug-or cell-loaded nanofilms for drug delivery or regenerative medicine purposes [25,26,37]. The application of nanofilms during surgical and medical procedures may be facilitated by using thick supporting layers coupled with the membranes.…”

“…3A. Previous studies have demonstrated that the thickness of ultra-thin polymeric films can be varied by simply regulating the spinning speed [22][23][24][25][26]. Fig.…”

“…Poly(L-lactic acid) (PLLA) has been demonstrated to be particularly suitable for the development of robust, yet highly flexible free-standing nanomembranes featured by optical transparency, low-cost and ease of fabrication (based on spin-assisted deposition) [22]. The potential of PLLA nanofilms for a series of biomedical applications has been recently highlighted, ranging from surgical sealing [23,24] to regenerative medicine [25] and drug delivery [26]. However, microporous PLLA nanofilms and their application in lab-on-chip systems have not been reported.…”

Pulsatile Drug Delivery System Triggered by Acoustic Radiation Force

“…Ordeig et al (2016) proposed a thermoresponsive hydrogel able to reversibly release the encapsulated drug after an overheating produced by US. Vannozzi et al (2016) proposed a US-responsive multilayer ultra-thin film based on poly(L-lactic acid) (PLLA) and polyelectrolytes. Responsivity to US was endowed by doping the PLLA layer with piezoelectric BaTiO3 nanoparticles.…”