Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Vysera Biomedical Limited, BMR House, Parkmore Business Park West, Galway, Ireland.
Int J Pharm. 2018 Sep 15;548(2):803-811. doi: 10.1016/j.ijpharm.2017.10.026. Epub 2017 Oct 13.
The purpose of the present study was to develop gefitinib-loaded polymeric foams that can be used as coating of drug-eluting stents for palliative treatment of bronchotracheal cancer. Release of such an anticancer drug from such stent coating can retard tumor regrowth into the bronchial lumen. Gefitinib-loaded polyurethane (PU) foams were prepared by embedding either gefitinib micronized crystals or gefitinib-loaded poly(lactic-co-glycolic acid) microspheres in water-blown films, with up to 10% w/w loading for gefitinib microcrystals and 15% w/w for gefitinib microspheres (corresponding to 1.0% w/w drug loading). Drug-release studies showed sustained release of gefitinib over a period of nine months, with higher absolute release rates at higher drug loading content. By the end of the studied nine month release periods, 60-100% of the loaded gefitinib had been released. Foams loaded with gefitinib-PLGA microspheres at 15% w/w showed accelerated drug release after 4 months, coinciding with the degradation of PLGA microparticles in the PU foam as demonstrated by scanning electron microscopy (SEM). When applied on a nitinol braided bronchotrachial stent, PU coatings with gefitinib microspheres showed similar mechanical properties as the drug-free PU coating, which indicated that the loading of microspheres did not affect the mechnical properties of the PU foams. In conclusion, we have fabricated drug-loaded PU foams that are suitable for bronchotracheal stent coating.
本研究旨在开发负载吉非替尼的聚合物泡沫,可作为载药支架的涂层,用于支气管肺癌的姑息性治疗。这种支架涂层释放的抗癌药物可以延缓肿瘤向支气管腔的再生。通过将吉非替尼微晶体或载有吉非替尼的聚乳酸-共-羟基乙酸(PLGA)微球嵌入水发泡薄膜中,制备了负载吉非替尼的聚氨酯(PU)泡沫,吉非替尼微晶体的载药量高达 10wt%,载药量为 15wt%的吉非替尼微球(相当于 1.0wt%的药物载药量)。药物释放研究表明,吉非替尼在九个月的时间内持续释放,药物载药量越高,绝对释放率越高。在研究的九个月释放期结束时,已释放了 60-100%的负载吉非替尼。以 15wt%负载吉非替尼-PLGA 微球的泡沫在四个月后显示出加速的药物释放,这与扫描电子显微镜(SEM)所示的 PLGA 微球在 PU 泡沫中的降解一致。当应用于镍钛诺编织支气管支架时,负载吉非替尼微球的 PU 涂层与无药物的 PU 涂层具有相似的机械性能,这表明微球的负载不会影响 PU 泡沫的机械性能。总之,我们已经制备了适合支气管支架涂层的负载药物的 PU 泡沫。