Design, Preparation, Drug Controlled Release Behavior Of Anti-Tumor Drug-Loaded Films

The non-vascular malignant tumors cause serious stenosis of tubularorgans. Stents are used to support occluded physiological tubular structures,but most bare metal stents still face restenosis and traditional drug-loadedstents have simple drug release behavior without any adjustment, so it’simportant to investigate drug controlled delivery systems of stent. In thisstudy, a series of anti-tumor drug-loaded films were designed to investigatedrug release behavior for controlled drug delivery systems of stent.Firstly,5-FU-loaded PCL films with a series of amphiphilicPCL-PEG-PCL copolymers were designed and prepared. PCL-PEG-PCL,5-FU, PCL were mixed and pressed into films by melting method and theeffects of copolymers addition on crystalline states, drug release behavior,drug diffusion, surface and internal morphologies of the films were studied.The results showed that the addition of PCL-PEG-PCL could adjust5-FU release behavior,5-FU release rate increased with the increasing content ofBlock2and decreasing ratio of PCL blocks in the PCL-PEG-PCLcopolymers. Compared to traditional PEG, PCL-PEG-PCL had a moreflexible regulating effect on drug release. The release of5-FU andPCL-PEG-PCL left pores in films which further increased the release rate of5-FU.In the second part of this study, a series of PTX-loaded PCL films weredesigned and prepared. Drug dissolution study and characteristics ofPVP/PTX solid dispersions (SDs) and physical mixtures (PMs) wereinvestigated and that PVP/PTX SDs were successfully prepared beforebeing incorporated in PCL films. Further more, the effect of application ofSDs on crystalline states, in vitro drug release, weightlessness study,morphologies of the films were investigated. The results showed that filmswith SDs showed a higher drug release rate than films with PMs or purePTX, also, the more content of PVP in films, the faster the drug wasreleased.Thirdly, two PVA-NCTD conjugates were designed and prepared forHACC film-based metal stent. IR images showed NCTD was successfullygrafted to PVA through ester group, the degree of grafting were8.6%and11.6%, PVA-NCTD had cell inhibition ability with a function on G2/M phase of Eca-109cell cycle. The hydrolysis rate of PVA-NCTD increasedwith pH values. The HACC films were prepared by solvent method and theeffects on in vitro drug release behavior and drug permeation of mucosae ofthe films were investigated. It was found that NCTD could release from oneside of the film, though the release of NCTD had a burst effect, the releaserate of HACC films with PVA-NCTD were still slower than that withNCTD. Also, compared to the results of in vitro drug release study, only46%NCTD in HACC films with PVA-NCTD was released in24h without theburst effect.