| Summary: | Hemodialysis vascular access dysfunction is the most significant cause of morbidity and hospitalisation in the hemodialysis industry. The main cause of hemodialysis vascular access dysfunction is venous stenosis incurred from neointimal hyperplasia. Current technologies employ the use of bare metal stents (BMS) or drug-eluting stents. However, overtime, restenosis occurs even after BMS is implanted. As a result, due to the development of an aggressive in-stent restenosis, the access site might be terminated.
This project aims to develop a sirolimus-coated hemodialysis stent that could potentially be applicable in the usage of hemodialysis vascular access dysfunction. In this study, the stents were coated using the ultrasonic spray coater, with 2 different solutions, PLC-sirolimus 80/20 and PLC-sirolimus 98/2. Spray coating conditions were calibrated to achieve 20µm thick coating and the samples’ coating thickness were confirmed using the Scanning Electron Microscope (SEM). The drug release study is carried out by immersing the samples in phosphate buffer saline (PBS) solution at a temperature of 37°C for a prolong period under stimulated biological environment. The PBS solutions in each samples will be renewed and the drug release and kinetic study of sirolimus is quantified using high performance liquid chromatography (HPLC) and the degradation profile is quantified by mass loss and gel permeation chromatography (GPC). A mechanical study will also be conducted to investigate the effect of a sirolimus coating on the mechanical properties of a stent cover.
In general, the drug release profiles for both PLC-sirolimus 80/20 and 98/2 coating shows desirable rate of release. However, the PLC-sirolimus 80/20 experienced a suppressed burst release from day 1, whereas, PLC-sirolimus 98/2 coating experienced a sudden burst release right from day 1. It was hypothesize that, this characteristics may be due to drug aggregates formed, during the drying phase of the coating. Scanning electron microscopy shows the presence of such drug aggregates. The results from mass loss study and GPC analysis showed minimal degradation of the polymer during the course of the drug release. The compressive test showed a drop in the maximum loading with increasing sirolimus loading. It was postulated that the addition of sirolimus reduced the entanglement of the polymer chains hence reducing the radial strength of the stent cover.
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