Yaqiong Zhang

In Vivo Evaluation of 5-Fluorouracil-Containing Self-Expandable Nitinol Stent in Rabbits: Efficiency in Long-Term Local Drug Delivery

This 5-fluorouracil (5-FU)-containing stent is fabricated by coating a film, composed of one 5-FU-containing ethylene-vinyl acetate (EVA) copolymer layer and one drug-free EVA protective layer, around a commercial self-expandable nitinol stent. The stents with various drug loadings were implanted into rabbit esophagus, and then 5-FU concentrations in the stent-touching and adjacent segments (including mucosa layer and muscle layer of each segment) of esophagus, serum, and liver were investigated throughout the experiment period. Quantitative analysis of 5-FU was performed by HPLC or LC-MS/MS, while the morphologies of esophageal mucosae by scanning electron microscopy (SEM). The results show that the 5-FU concentration in stent-touching esophageal tissue is overwhelmingly higher than that in serum or liver at all the investigation time points until 45 days. The 5-FU concentration in the stent-touching segment is higher than those in the other segments of esophagus, while the 5-FU concentration in mucosa layer is higher than that in muscle layer for the same segment. With the increase of drug loading, the drug concentrations in esophageal tissues and serum increase, and cellular desquamation of stent-touching epithelial surface become increasingly severe by SEM. Based on the results, the 5-FU-loaded esophageal stent operates long-term local drug delivery with great efficiency.

Effects of implant diameter, drug loading and end-capping on praziquantel release from PCL implants

Praziquantel (PZQ)-loaded poly(epsilon-caprolactone) (PCL) cylindrical implants were fabricated and characterized. Implant diameter (3, 4 and 8mm), drug loading (25% and 50%), and the end-capping were investigated to evaluate their effects on drug release. The evolution of implants with release time was conducted in terms of implant microstructure, crystallinity, drug content and molecular weight of PCL. The results showed that drug release was fastest for the implant with a diameter of 3mm and slowest for the implant with a diameter of 8mm; drug release from the implant with a drug content of 50% was faster than that from the implant with a drug content of 25%; the release of PZQ from the end-capped implants was slightly slower than that from the corresponding end-uncapped implants. The effect of drug loadings on PZQ release was related with diameter of the implants and the effect was weakened as diameter of the implants increased. The drug release data for all the implants were best fitted with Ritger-Peppas model, therefore Fickian diffusion was the predominant release mechanism. The evolution of implants with release time verified that PZQ was gradually released from the exterior to the interior of the implants.

Study on the preparation and properties of copolyimides based on hexafluoroisopropylidene bis(3,4-phthalic anhydride) and 1,12-di(4-aminophenoxy)dodecane

Abstract Copolyimides were prepared from hexafluoroisopropylidene bis(3,4-phthalic anhydride) (6FDA), 1,12-di(4-aminophenoxy)dodecane and 4,4′-diaminodiphenylether through a solution co-polycondensation reaction followed by a chemical imidization reaction. It was observed that copolyimides prepared with any diamine molar ratio studied (1,12-di(4-aminophenoxy)dodecane/4,4′-diaminodiphenylether=7/3∽1/9) were soluble in polar organic solvents such as N-methyl-2-pyrrolidone (NMP), N,N-dimethylacetamide (DMA), dimethylformamide (DMF) and m-cresol, tetrahydrofuran (THF) and chloroform, while the corresponding homopolyimides were insoluble. Wide angle X-ray diffraction (WAXD) results show a clear relationship between the crystallinity tendency and the solubility of polyimides. High crystallinity tendency leads to low organo-solubility. The glass transition temperature of a copolyimide was in good agreement with Fox’s equation for random copolymers. The long flexible chains in the backbone of copolyimides are the least thermally stable part.

Study on hydrophilic 5-fluorouracil release from hydrophobic poly(ϵ-caprolactone) cylindrical implants

Hydrophilic 5-fluorouracil (5-FU) loaded cylindrical poly(ϵ-caprolactone) (PCL) implants with different implant diameters (2, 4 and 8u2009mm), different drug loadings (25% and 50%) and end-capping were fabricated and characterized. The implant structure, drug content and molecular weight of PCL after 120 days drug release were investigated. The in vitro release results showed that, when the drug loading was the same, drug release was fastest for the implant with a diameter of 2u2009mm and slowest for the implant with a diameter of 8u2009mm; for the implants with the same diameters, the release of drug from the implants with 50% drug loading was faster than that from the implants with 25% drug loading; however, this effect of drug loading decreased with the increase of implant diameter; in addition, 5-FU was released slightly slower from the end-capped implants than from the corresponding uncapped implants; the drug release data for all the uncapped implants were best fit with the Ritger-Peppas model. Drug release from the hydrophobic implants was found to be dominated by diffusion mechanism. Scanning electron microscopy images and drug content measurements revealed that 5-FU release took place gradually from the exterior region to the interior region of the implants.

Tyrosine kinase inhibitor loaded PCL microspheres prepared by S/O/W technique using ethanol as pretreatment agent

A new tyrosine kinase inhibitor (denoted as CH331) and its poly(epsilon-caprolactone) (PCL) microspheres were studied. The CH331 particles were pretreated with ethanol and then used to prepare CH331 loaded PCL microspheres by S/O/W solvent evaporation technique. Solubility values of CH331 in several organic and aqueous media were measured. The amount of ethanol and CH331 solubility play a significant role in drug loading, encapsulation efficiency, mean diameter and morphology of the microspheres, crystallinity and in vitro drug release. The treatment with a suitable amount of ethanol leads to more uniform sizes, better appearance and higher encapsulation efficiency for the microspheres. Compared with 0.5% PVA phosphate buffer solution (pH 7.4), 0.5% PVA aqueous solution as outer aqueous phase lowers encapsulation efficiency of microspheres, however, improves the drug release behavior.