Preparation of a Microporous Polyurethane Film with Negative Surface Charge for siRNA Delivery via Stent

Abstract

Polyurethane (PU) and polyethylene glycol (PEG) were used to prepare a porous stent-covering material for the controlled delivery of small interfering RNA (siRNA). Microporous polymer films were prepared using a blend of polyurethane and water-soluble polyethylene glycol by the solution casting method; the PEG component was extracted in water to make the film microporous. This film was dipped in 2% poly(methyl methacrylate-co-methacrylic acid) solution to coat the polymer film with the anionic polyelectrolyte. The chemical components of the film surface were characterized by Fourier Transform Infrared (FTIR) spectroscopy and its structural morphology was examined by scanning electron microscopy (SEM). The effect of the negatively charged surface after attachment of a fluorescein isothiocyanate- (FITC-) labeled siRNA-polyethyleneimine complex onto the microporous polyurethane film and the controlled release of the complex from the film was investigated by fluorescence microscopy. Fluorescence microscopy showed the PU surface with intense fluorescence by the aggregates of the FITC-labeled-siRNA-PEI complex (measuring up to few microns in size); additionally, the negatively charged PU surface revealed broad and diffuse fluorescence. These results suggest that the construction of negatively charged microporous polyurethane films is feasible and could be applied for enhancing the efficiency of siRNA delivery via a stent-covering polyurethane film.

Development and In Vitro Evaluation of 5-Fluorouracil-Eluting Stents for the Treatment of Colorectal Cancer and Cancer-Related Obstruction

“…The spectrum of pure 5FU exhibited characteristic peaks at ~2940, 1740, 1250 and 1230 cm −1 consistent with C–H, C=O, C–N and C–F stretching vibrations, respectively, and at ~825 cm −1 consistent with C-H deformation [ 32 , 59 , 60 , 61 ]. For PU coatings (drug-free), the spectrum revealed peaks at ~3330, 2930, 1740 and 1270 cm −1 corresponding to N–H, C–H, C=O and C–O stretching vibrations, and consistent with the reported aliphatic polycarbonate-PU structure [ 62 , 63 , 64 , 65 ]. In comparison, the spectrum of the PU 5FU coating (basecoat) included all of the characteristic peaks of the PU with a slight broadening of peaks at ~1280 and 814 cm −1 due to the presence of 5FU, indicating its successful inclusion into the PU matrix without any apparent changes in their corresponding chemical structures.…”

Targeted Delivery of Bioactive Molecules for Vascular Intervention and Tissue Engineering

“…Many new molecules also hold promise for improving future drug-eluting stent designs. The possibility of delivering small-interfering ribonucleic acid (siRNA delivery) is currently being investigated ( Hossfeld et al, 2013 ; Che et al, 2016 ; Cho and Park, 2017 ). siRNA are short double-stranded RNA molecules that interfere with the expression of specific genes.…”

The Use of Bioactive Polymers for Intervention and Tissue Engineering: The New Frontier for Cardiovascular Therapy

“…Many new molecules have appeared on the scene for possible use and promise to improve future drug-eluting stent models. Among these, very promising and under current investigation are the gene-eluting stents that can provide small interfering ribonucleic acid with siRNA release [ 68 , 107 , 108 ]. In this way, the stents that make use of embedded siRNA (RNA molecules impeding target gene expression) have as their objective a modulating effect on the receptors of the adhesion molecules to reduce thrombosis and inflammation [ 68 ] or to suppress the proliferation of SMCs, useful for preventing restenosis [ 85 ].…”