Y. Bedulho das Lages , N. Milanino , J. Verin , J.F. Willart , F. Danede , C. Vincent , P. Bawuah , J.A. Zeitler , F. Siepmann , J. Siepmann
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Its release was measured into artificial perilymph, and the systems were thoroughly characterised before and after exposure to the medium by optical and scanning electron microscopy, SEM-EDX analysis, DSC, X-ray powder diffraction, X-ray microtomography and texture analysis. Notably, the resulting drug release rates were much higher than from <em>silicone</em>-based implants of similar size. Furthermore, varying the vinyl acetate content allowed for adjusting the desired release patterns effectively: With decreasing vinyl acetate content, the crystallinity of the copolymer increased, and the release rate decreased. Interestingly, the drug was homogeneously distributed as tiny crystals throughout the polymeric matrices. Upon contact with aqueous fluids, water penetrates the implants and dissolves the drug, which subsequently diffuses out of the device. 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引用次数: 0
摘要
这项研究评估了聚(乙烯-醋酸乙烯)(EVA)共聚物在微型植入物中作为基质形成剂的潜力,从而实现向内耳可控给药。由于存在血液-耳蜗屏障,在临床实践中不可能将药物可靠地输送到这个微小且高度敏感的器官。为了克服这一瓶颈,我们通过热熔挤压法制备了不同的 EVA 植入物,并改变了醋酸乙烯酯的含量和植入物的直径。地塞米松是一种具有抗炎和抗纤维化活性的药物。通过光学显微镜和扫描电子显微镜、扫描电子显微镜-EDX 分析、DSC、X 射线粉末衍射、X 射线显微层析和纹理分析,对系统暴露于介质前后的特性进行了全面分析。值得注意的是,与类似大小的硅基植入物相比,药物释放率要高得多。此外,通过改变醋酸乙烯酯的含量,可以有效调整所需的释放模式:随着醋酸乙烯含量的降低,共聚物的结晶度增加,释放率降低。有趣的是,药物以微小晶体的形式均匀分布在整个聚合物基质中。在与水性液体接触时,水会渗透植入物并溶解药物,随后药物会从装置中扩散出来。重要的是,在暴露于释放介质长达 10 个月的时间里,无论 EVA 的等级如何,都没有观察到明显的系统膨胀或收缩现象。此外,植入物的机械性能既不会过于柔韧,也不会过于僵硬,因此可以在患者的内耳中使用。
EVA implants for controlled drug delivery to the inner ear
This study evaluated the potential of poly(ethylene vinyl acetate) (EVA) copolymers as matrix formers in miniaturised implants, allowing to achieve controlled drug delivery into the inner ear. Due to the blood-cochlea barrier, it is impossible to reliably deliver a drug to this tiny and highly sensitive organ in clinical practice. To overcome this bottleneck, different EVA implants were prepared by hot melt extrusion, altering the vinyl acetate content and implant diameter. Dexamethasone was incorporated as a drug with anti-inflammatory and anti-fibrotic activity. Its release was measured into artificial perilymph, and the systems were thoroughly characterised before and after exposure to the medium by optical and scanning electron microscopy, SEM-EDX analysis, DSC, X-ray powder diffraction, X-ray microtomography and texture analysis. Notably, the resulting drug release rates were much higher than from silicone-based implants of similar size. Furthermore, varying the vinyl acetate content allowed for adjusting the desired release patterns effectively: With decreasing vinyl acetate content, the crystallinity of the copolymer increased, and the release rate decreased. Interestingly, the drug was homogeneously distributed as tiny crystals throughout the polymeric matrices. Upon contact with aqueous fluids, water penetrates the implants and dissolves the drug, which subsequently diffuses out of the device. Importantly, no noteworthy system swelling or shrinking was observed for up to 10 months upon exposure to the release medium, irrespective of the EVA grade. Also, the mechanical properties of the implants can be expected to allow for administration into the inner ear of a patient, being neither too flexible nor too rigid.
期刊介绍:
International Journal of Pharmaceutics: X offers authors with high-quality research who want to publish in a gold open access journal the opportunity to make their work immediately, permanently, and freely accessible.
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The International Journal of Pharmaceutics is the second most cited journal in the "Pharmacy & Pharmacology" category out of 358 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.