5-Fluorouracil-loaded multilayered films for drug controlled releasing stent application: Drug release, microstructure, and ex vivo permeation behaviors.
A series of poly(epsilon-caprolactone) (PCL)-based multilayered films containing antitumor 5-fluorouracil as stent struts were produced. A backing layer and a surface drug layer were applied to the main drug layer to realize unidirectional, controlled drug release and enhance the mechanical properties. The intricate multilayered structure endowed the films with flexibility to regulate drug release. The in vitro release results showed that drug release was dependent on the drug loading and environmental pH, and could also be effectively regulated by addition of hydrophilic PEG as pore forming agent. Drug release from the multilayered film was found to be dominated by diffusion mechanism. Rapid PEG release led to the formation of pores and the resulting fast drug release. SEM images revealed that the 5-FU crystalline particles were homogeneously dispersed in the film, and there emerged many pores on the surface and in the bulk of film after PEG and drug release, indicating that the porous structure of film was formed and gradually evolved with drug and PEG release. Ex vivo permeation behaviors of drug from the film through porcine esophageal mucosa were in high correlation with the in vitro release behaviors, and the permeation rate was determined by the release of drug from film. With the virtue of releasing drug in a unidirectional and controlled manner, the multilayered films provide an attractive mode to produce polymeric drug delivery stents for localized treatment of stenosis or occlusion.
Lei
Lei
L
School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Liu
Xi
X
Guo
Shengrong
S
Tang
Mufei
M
Cheng
Liang
L
Tian
Ling
L
D000818:Animals; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D054855:Drug-Eluting Stents; D004848:Epithelium / Q000378:metabolism; D004947:Esophagus / Q000378:metabolism; D005472:Fluorouracil / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D055595:Mechanical Phenomena; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D010539:Permeability; D011091:Polyesters / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties; D013552:Swine
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; C016240:polycaprolactone; D005472:Fluorouracil