Zero-order release of 5-fluorouracil from PCL-based films featuring trilayered structures for stent application

A trilayered Poly(ε-caprolactone) (PCL)-based film with a coating layer (CL), a drug-storing layer (DSL) loaded with antitumor drug 5-Fluorouracil (5-FU) and a backing layer (BL) are presented for film-based stent application in malignant stricture or stenosis. V-C diffusion cells were used to investigate the drug permeability of the CL, while scanning electron microscopy (SEM) was employed for observing the microscopic architectures and morphologies. Drug release from the trilayered films exhibited a zero-order pattern, and the release process followed an ‘outer-to-inner’ pattern. The formation mechanism and influencing factors of the zero-order drug release pattern were in-depth elucidated, and factors affecting the drug release were also investigated. The reduction of initial drug loading in DSL slowed the drug release and diminished the zero-order release pattern. Drug permeability of the CL depended significantly on CL thickness, but not significantly on PCL molecular weight. Besides, the addition of PEG porogen in the CL accelerated the drug release by elevation of the drug permeability of CL, and the action mechanism of PEG was revealed by the PEG release test and SEM. The loading of 5-FU in the CL could lead to a two-phased release profile. This study revealed the potential of the trilayered film in controlled drug delivery to intraluminal tumor due to its highly tunable zero-order drug release.

The trilayered PCL films can load drug in the middle layer or in both the middle layer and the top coating layer, and they can release drug in highly tunable behaviors (in some cases, in zero-order manners). The drug release can be adjusted by changing the compositions of the three separate layers.Figure optionsDownload as PowerPoint slide