Preparation, Characterization And Evalution Of Poly (ε-Caprolactone)-Based Films Incorporated With Paclitaxel/5-Fluorouracil

Stent performed as an ideal drug delivery devices due to its dual functions of supporting the lumen and treating local intraluminal tumor or preventing the restenosis by releasing drug. Poly (ε-caprolactone) (PCL), a kind of biodegradable aliphatic polyester, has many advantageous properties, including good drug permeability, good biocompatibility. 5-fluorouracil (5-FU) and paclitaxel (PTX) are both widely used in the treatment of cancer. Currently, many DESs loaded with single 5-FU or PTX are developed, however, few DESs co-loaded with 5-FU and PTX are reported.In this study, PCL based films co-loaded with 5-FU and PTX were prepared. They were investigated by X-ray diffraction analysis (XRD) and scanning electronic microscopy (SEM). Generally speaking, the surfaces of the films were smooth and flat and the 5-FU and PTX contents of drug-loaded films are homogeneous. And a gradient elution HPLC analytical method used for simultaneous quantification of 5-FU and PTX was developed.Bi-layered films (consisted of drug-loaded layer and backing layer) and tri-layered films (consisted of surface layer, drug-loaded layer and backing layer) were designed and fabricated. The amounts of 5-FU and PTX permeated through the backing layer were almost zero, which were much lower than those of 5-FU and PTX released from the drug-loaded layer, indicating that the multi-layered structure endowed the film with drug release in unidirectional pattern. Drug loading, the ratio of 5-FU/PTX, the composition of surface layer, the addition of hydrophilic PEG and the architecture of the stent films were investigated to evaluate their effects on drug release. The results showed that drug loading had no significant influence on drug release from PCL films; the added PEG could promote drug release from PCL films with relative high drug loadings; Under the same condition of total drug loading, the release of 5-FU and PTX could be adjusted by altering the ratio of 5-FU/PTX (when the ratio of 5-FU/PTX was high, the drug releases were fast); agglutinating surface layer with different compositions onto the bi-layered films could effectively tune the drug releases from the inner layer, and the release data was best fitted with Ritger–Peppas model, indicating Fickian diffusion was the predominant release mechanism. And the in vivo drug release results showed that the in vivo drug release was highly correlative with the in vitro drug release.We also explored the cytotoxicity of the films. The MTT test results indicated that the PCL-based films co-loaded with 5-FU and PTX had higher inhibition ratios on Eca-109 cells than films loaded with 5-FU or PTX alone.