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

Abstract

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.

Gefitinib loaded PLGA and chitosan coated PLGA nanoparticles with magnified cytotoxicity against A549 lung cancer cell lines

“…4 . Pure GFT showed characteristic intense peaks at 19.3°, 20.6°, 22.5°, 24°, 38.1° and 44.3° as reported in literature ( Chen et al, 2017 ). The sharp peaks of GFT disappeared completely in GFT loaded PLGA-NPs and GFT loaded CS-PLGA-NPs, indicating that GFT was dispersed molecularly with the polymer in NPs.…”

“…However, due to charge attraction between drug and chitosan in GFT loaded CS-PLGA-NPs exhibited more sustained release of drug in comparison to GFT loaded PLGA-NPs ( Fig. 5 ) ( Chen et al, 2017 ). The release data was fitted to various kinetic models in order to know release mechanism of GFT from GFT loaded PLGA-NPs and GFT loaded CS-PLGA-NPs.…”

Biomedical applications of polyurethane materials and coatings

“…The chemotherapy drug gefitinib has been embedded between PU support and top layers using spray coating to form a drug-eluting stent for bronchotracheal cancer; 44 when the drug was embedded as crystals, release was recorded for 7-21 days, but when embedded into poly(lactic-co-glycolic acid) (PLGA) microspheres, a sustained release >6 months was noted (Fig. 4).…”

“…(a) Release of tumour suppressing drug gefitinib from PU constructs loaded with gefitinib-PLGA microspheres; (b) schematic of bronchotracheal stent to provide long-term release of this drug 44. …”

In vitro study of drug release from various loaded polyurethane samples and subjected to different non-pulsed flow rates

“…They have concluded the drug was released with a diffusion mechanism, where it was observed that the drug release rate is increased with the drug content. There are some devices to better control drug release profiles, like the use of drug delivery carriers [21], micro-sponges for hydrophobic drugs [22], or the use of barriers layers of a polymer without drug [16,23]. In the study [13], Vahedi et al have revealed that the flow conditions influence the release profile by acting on the penetration depth of the fluid.…”