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吉非替尼释放在治疗支气管癌的药物洗脱支架中的泡沫型聚氨酯的制备及性能表征。

Fabrication and characterization of gefitinib-releasing polyurethane foam as a coating for drug-eluting stent in the treatment of bronchotracheal cancer.

机构信息

Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.

Vysera Biomedical Limited, BMR House, Parkmore Business Park West, Galway, Ireland.

出版信息

Int J Pharm. 2018 Sep 15;548(2):803-811. doi: 10.1016/j.ijpharm.2017.10.026. Epub 2017 Oct 13.

Abstract

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.

摘要

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。

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