Local Delivery of Antiproliferative Agents via Stents

Kwon, Hyuck Joon; Park, Sangsoo

doi:10.3390/polym6030755

Cited by 20 publications

(16 citation statements)

References 75 publications

(96 reference statements)

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“…Stent insertion can be a lifesaving procedure affording dramatic, emergent relief of acute respiratory distress from airway obstruction resulting extended survival (Hohenforst-Schmidt et al, 2016;Shaffer and Allen, 1998). PU membrane generally has a high tensile strength allowing them as a covering material for bronchotracheal stents that are compressed inside an introducer tube with a minimum volume during the delivery to the obstructed lumen (Kwon and Park, 2014;Lamba et al, 1997;Seo and Na, 2014). Anti-cancer drugs loaded in PU polymeric coating of stents are locally released to inhibit the growth of the tumor while simultaneously minimizing systemic drug exposure (Puranik et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Gefitinib/gefitinib microspheres loaded polyurethane constructs as drug-eluting stent coating

Chen

Clauser

Thiebes

et al. 2017

European Journal of Pharmaceutical Sciences

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One of the complications of bronchotracheal cancer is obstruction of the upper airways. Local tumor resection in combination with an airway stent can suppress intraluminal tumor (re)growth. We have investigated a novel drug-eluting stent coating for local release of the anticancer drug gefitinib. A polyurethane (PU) sandwich construct was prepared by a spray coating method in which gefitinib was embedded between a PU support layer of 200 μm and a PU top layer of 50-200 μm. Gefitinib was either embedded in the construct as small crystals or as gefitinib-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MSP). The drug was incorporated in the PU constructs with high recovery (83-93%), and the spray coating procedure did not affect the morphologies of the embedded microspheres as demonstrated by scanning electron microscopy (SEM), confocal laser scanning microscopy and fluorescence microscopy analysis. PU constructs loaded with gefitinib crystals released the drug for 7-21 days and showed diffusion based release kinetics. Importantly, directional release of the drug towards the top layer, which is supposed to face the tumor mass, was controlled by the thicknesses of the PU top layer. PU constructs loaded with gefitinib microspheres released the drug in a sustained manner for N 6 months indicating that drug release from the microspheres became the rate limiting step. In conclusion, the sandwich structure of drug-loaded PLGA microspheres in PU coating is a promising coating for airway stents that release anticancer drugs locally for a prolonged time.

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Section: Introductionmentioning

confidence: 99%

Gefitinib/gefitinib microspheres loaded polyurethane constructs as drug-eluting stent coating

Chen

Clauser

Thiebes

et al. 2017

European Journal of Pharmaceutical Sciences

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“…To prevent excessive tissue hyperplasia and the resulting reobstruction of the stented lumen, localized drug delivery via the stent has been attempted, and many antiproliferative drugs, including sirolimus and paclitaxel, are proven effective for lowering the restenosis rate of the procedure. In addition to antiproliferative drugs, some small interfering RNAs (siR-NAs) have been effectively employed to suppress tissue hyperplasia after stenting [12][13][14][15]. siRNAs can be incorporated into a stent-covering for localized siRNA delivery to the tissue around the stent.…”

Section: Introductionmentioning

confidence: 99%

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

Cho

Park

2017

International Journal of Polymer Science

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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.

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“…Published data from meta-analyses and clinical trials comparing DES to BMS suggested higher rates of late clinical events in patients receiving DES [ 14 – 17 ]. The antiproliferative drugs released by DES interfere with the natural vascular healing process by arresting the endothelial cell proliferation and growth on the stent surface [ 18 ]. Late (30 days – 1 year) and very late (>1 year) stent thrombosis are the major clinical consequences of impeded endothelial healing in patients receiving DES [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Surface Modification of Biodegradable Polymers towards Better Biocompatibility and Lower Thrombogenicity

et al. 2015

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PurposeDrug-eluting stents (DES) based on permanent polymeric coating matrices have been introduced to overcome the in stent restenosis associated with bare metal stents (BMS). A further step was the development of DES with biodegradable polymeric coatings to address the risk of thrombosis associated with first-generation DES. In this study we evaluate the biocompatibility of biodegradable polymer materials for their potential use as coating matrices for DES or as materials for fully bioabsorbable vascular stents.Materials and MethodsFive different polymers, poly(L-lactide) PLLA, poly(D,L-lactide) PDLLA, poly(L-lactide-co-glycolide) P(LLA-co-GA), poly(D,L-lactide-co-glycolide) P(DLLA-co-GA) and poly(L-lactide-co-ε-caprolactone), P(LLA-co-CL) were examined in vitro without and with surface modification. The surface modification of polymers was performed by means of wet-chemical (NaOH and ethylenediamine (EDA)) and plasma-chemical (O2 and NH3) processes. The biocompatibility studies were performed on three different cell types: immortalized mouse fibroblasts (cell line L929), human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC). The biocompatibility was examined quantitatively using in vitro cytotoxicity assay. Cells were investigated immunocytochemically for expression of specific markers, and morphology was visualized using confocal laser scanning (CLSM) and scanning electron (SEM) microscopy. Additionally, polymer surfaces were examined for their thrombogenicity using an established hemocompatibility test.ResultsBoth endothelial cell types exhibited poor viability and adhesion on all five unmodified polymer surfaces. The biocompatibility of the polymers could be influenced positively by surface modifications. In particular, a reproducible effect was observed for NH3-plasma treatment, which enhanced the cell viability, adhesion and morphology on all five polymeric surfaces.ConclusionSurface modification of polymers can provide a useful approach to enhance their biocompatibility. For clinical application, attempts should be made to stabilize the plasma modification and use it for coupling of biomolecules to accelerate the re-endothelialization of stent surfaces in vivo.

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Local Delivery of Antiproliferative Agents via Stents

Cited by 20 publications

References 75 publications

Gefitinib/gefitinib microspheres loaded polyurethane constructs as drug-eluting stent coating

Gefitinib/gefitinib microspheres loaded polyurethane constructs as drug-eluting stent coating

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

Surface Modification of Biodegradable Polymers towards Better Biocompatibility and Lower Thrombogenicity

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