Search

An antitumor drug/esophagus stent combination can palliatively relieve malignant esophageal stricture and exert local chemotherapy to cancer. It is vital for effective treatment of cancer to control drug release and facilitate drug penetration into deep tissue after the combination is placed in the malignant strictured esophagus part. In this study, we firstly designed and prepared a novel antitumor drug/esophagus stent combination: a magnetocaloric nitinol stent coated with a bilayered film that consisted of one ethylene-vinyl acetate copolymer (EVA) layer as drug blocking layer and one EVA layer containing 10% paclitaxel (PTX) and 30% temperature sensitive phase-change fatty alcohol (1-tetradecanol, 1-hexadecanol or 1-octadecanol). The drug release and penetration into rabbit esophagus wall from the combination were investigated. It was found that, under an alternating electromagnetic field at a power of 0.1 kW, the combination was heated to 43 °C, the PTX was faster and more released from the combination, as well as the amount of PTX in esophagus tissue or its deep muscle tissue penetrated from the combination was much higher than that without alternating electromagnetic field. The pathological data showed that the combination was biocompatible and safe after placement in rabbit esophagus even under an alternating electromagnetic field. Overall, the PTX could be magnetocalorically released and effectively penetrated into esophagus wall from the PTX/nitinol stent combination., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Here we report the application of solid dispersion (SD) technique to improve paclitaxel (PTX) release from poly(ϵ-caprolactone) (PCL)-based film. Paclitaxel solid dispersions (SDs) with either poloxamer188 (PXM) or polyethylene glycol (PEG) were successfully prepared by a melting method and then incorporated into PCL films, which were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and In vitro drug release/dissolution studies. It was found that PTX was faster released from the SDs than the corresponding physical mixtures (PMs) or PTX alone. For the PCL films with almost the same PTX loading, drug release from films containing SDs was remarkably faster than that from the film directly incorporated with PTX particles, and the films containing SDs with PXM exhibited a faster drug release than those with PEG. An increase In the content of PXM had no significant influence on PTX release from the films containing SDs. Incorporation of a higher content of SDs led to slower drug release from PCL films, indicating that PTX loading had a dominating effect on drug release. Through this study, we demonstrated the feasibility of the application of SD technique on the improvement of PTX release from PCL films and offered some beneficial information on modulating drug release behavior by changing the compositions and contents of the SDs-loaded PCL films.

Abstract: In this study, partially hydrolyzed ethylene vinyl acetate (EVA) copolymers with three hydrolysis degrees (12.2%, 32.6% and 46.9%) were obtained by alkaline hydrolysis of EVA copolymer, characterized by Fourier-transform infrared spectroscopy (FTIR), 1H NMR and gel permeation chromatography (GPC). Paclitaxel-loaded and drug-free films based on the partially hydrolyzed EVA copolymers were fabricated. The swelling behaviors, crystallinities, mechanical properties of the fabricated films were investigated, and the effects of hydrolysis degree, film thickness and drug loading dose on in vitro drug release from the films were also investigated. In vitro swelling study showed that the swelling of partially hydrolyzed EVA films was greater than the EVA film and the film with higher hydrolysis degree swelled more intensively. X-ray diffraction (XRD) results exhibited that the crystallinity of the polymer increased with increasing hydrolysis degree. In paclitaxel-loaded EVA film, a part of paclitaxel was in crystalline form; while in paclitaxel-loaded partially hydrolyzed EVA films, paclitaxel was distributed in amorphous form or molecularly dispersed. In the in vitro drug release test, the film with higher hydrolysis degree and smaller thickness released paclitaxel more quickly. With higher drug loading dose, the drug release rate was larger. The partially hydrolyzed EVA films were applied for drug delivery systems for the first time, and demonstrated to have great capability of controlling drug release thanks to the adjustable hydrolysis degree. [ABSTRACT FROM AUTHOR]

Abstract A novel layer by layer (LbL) assembled structure with phosphorylcholine groups was fabricated to improve the hemocompatibility of paclitaxel/chitosan (PTX/CS) nanofibers (NF) coatings The random copolymers with phosphorylcholine groups poly (2‑methacryloyloxy-ethylphosphorylcholine‑ co ‑methacrylicacid) (PMAs) were synthesized through free radical polymerization and then first PMA layer formed on PTX/CS NF coatings via electrostatic interactions. After that CS polycation and PMA polyanion thin films LbL formed on PTX/CS NF coatings. The LbL structure was confirmed by X-ray photoelectron spectroscopy (XPS) and water contact angle. The drug release in vitro indicated that the PMA modified PTX/CS NF coatings (PTX/CS-PMA NF coatings) showed a sustained slower release of PTX drug. The LbL coatings containing phosphorylcholine groups could significantly reduce proteins adsorption, platelets adhesion and cell adhesion. They showed a lower platelet (about 6%) and protein (30–40%) (bovine serum albumin, BSA; bovine plasma fibrinogen, Fg) adhesion. Meanwhile, the adhesion of human umbilical vein endothelial cells (HUVECs) was also found reduced. These results demonstrate that the preparation of PMA modified coatings is a simple strategy to improve the hemocompatibility of PTX/CS NF coatings, has good potential for application in blood-contacting materials and devices. Statement of significance We develop a simple method to improve the hemocompatibility of paclitaxel/chitosan (PTX/CS) nanofibers (NF) coatings, which can significantly reduce the protein adsorption, and the adhesion of cells and platelets. Using layer by layer (LbL) assembly with PMA polyanion and CS polycation, multilayered PMA/CS films formed on the PTX/CS NF coatings. The X-ray photoelectron spectroscopy (XPS) and water contact angle characterization demonstrated that a cell outer membrane mimetic structure was formed on the PTX/CS NF coatings. The hemocompatibility of modified surface was significantly improved as shown by 94% adhesion suppression for platelets and 60–70% adsorption suppression for bovine plasma fibrinogen (Fg) and bovine serum albumin (BSA). The drug release in vitro indicated that the PMA modified PTX/CS NF (PTX/CS-PMA) coatings had a sustained drug release. Thus this paper provides a facile method for fabricating cell outer membrane mimetic structure which can improve hemocompatibility of blood-contacting material surfaces. Graphical abstract Unlabelled Image Highlights • Using LbL assembly, PTX/CS-PMA NF coatings were fabricated to mimic cell outer membrane structure. • The PTX/CS-PMA NF coatings are capable of reducing protein adsorption, cell adhesion and platelet adhesion. • The PTX/CS-PMA NF coatings would a promising strategy to improve biocompatibility of blood-contacting material surfaces. [ABSTRACT FROM AUTHOR]