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Electrospun nanofibers - A promising solid in-situ gelling alternative for ocular drug delivery.
European Journal of Pharmaceutics and Biopharmaceutics ( IF 4.9 ) Pub Date : 2019-12-07 , DOI: 10.1016/j.ejpb.2019.11.012
Benedikt Göttel 1 , Juliana Martins de Souza E Silva 2 , Cristine Santos de Oliveira 2 , Frank Syrowatka 3 , Miltiadis Fiorentzis 4 , Anja Viestenz 4 , Arne Viestenz 4 , Karsten Mäder 1
Affiliation  

A serious problem of the treatment of eye diseases is the very short residence time of the drug. The majority of the drug is cleared within few seconds due to the poor capability of the eye to accommodate additional liquids. We developed a new ocular drug delivery system, which is applied in dry form and forms immediately a gel after administration. The system is based on gellan gum/pullulan electrospun nanofibers. The rheological behavior of the spinning solution was investigated followed by further characterization of the in situ formed gel. Three-dimensional X-ray imaging with nanometric resolution (nano-CT) and electron scanning microscopy were used for a detailed characterization of the diameter and alignment of the fibers. A high porosity (87.5 ± 0.5%) and pore interconnectivity (99%) was found. To ensure a good fit to the eye anatomy, the prepared fibers were shaped into curved geometries. Additionally, a new innovative moistening chamber for the in vitro determination of the ocular residence time in porcine eyes was developed which mimics the tear turnover. A clear prolongation of the fluorescein residence time compared to conventional eye drops was achieved with the application of the curved nanofiber in situ gelling mat. In summary, the developed in situ gelling system with adapted geometry is a promising alternative system for ocular drug delivery.

中文翻译:

电纺纳米纤维-一种用于眼部药物递送的有前途的固体原位胶凝替代物。

眼病治疗的一个严重问题是药物的停留时间非常短。由于眼睛容纳其他液体的能力较弱,因此大多数药物会在几秒钟内被清除。我们开发了一种新型的眼部药物递送系统,该系统以干燥形式应用,并在给药后立即形成凝胶。该系统基于结冷胶/普鲁兰电纺纳米纤维。研究了纺丝溶液的流变行为,然后进一步表征了原位形成的凝胶。使用具有纳米分辨率(nano-CT)的三维X射线成像和电子扫描显微镜来详细表征纤维的直径和排列。发现高孔隙率(87.5±0.5%)和孔隙互连性(99%)。为确保与眼部解剖结构良好吻合,将制备的纤维成形为弯曲的几何形状。此外,开发了一种新的创新性润湿腔室,用于体外测定猪眼中的眼部停留时间,该腔室模拟了泪液的周转时间。通过使用弯曲的纳米纤维原位凝胶垫,与常规滴眼剂相比,荧光素的停留时间明显延长。总之,开发的具有合适几何形状的原位胶凝系统是用于眼部药物递送的有前途的替代系统。通过使用弯曲的纳米纤维原位凝胶垫,与常规滴眼剂相比,荧光素的停留时间明显延长。总之,开发的具有合适几何形状的原位胶凝系统是用于眼部药物递送的有前途的替代系统。通过使用弯曲的纳米纤维原位凝胶垫,与常规滴眼剂相比,荧光素的停留时间明显延长。总之,开发的具有合适几何形状的原位胶凝系统是用于眼部药物递送的有前途的替代系统。
更新日期:2019-12-07
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