Beyer Susanne, Xie Li, Gräfe Susanna, Vogel Vitali, Dietrich Kerstin, Wiehe Arno, Albrecht Volker, Mäntele Werner, Wacker Matthias G
Institute of Pharmaceutical Technology,, Goethe University, Max-von-Laue-Str. 9,, 60438, Frankfurt (Main), Germany.
Pharm Res. 2015 May;32(5):1714-26. doi: 10.1007/s11095-014-1569-y. Epub 2014 Nov 19.
Industrial production of nanosized drug delivery devices is still an obstacle to the commercialization of nanomedicines. This study encompasses the development of nanoparticles for peroral application in photodynamic therapy, optimization according to the selected product specifications, and the translation into a continuous flow process.
Polymeric nanoparticles were prepared by nanoprecipitation of Eudragit® RS 100 in presence and in absence of glycofurol. The photosensitizer temoporfin has been encapsulated into these carrier devices. Process parameters were optimized by means of a Design of Experiments approach and nanoparticles with optimal characteristics were manufactured by using microreactor technology. The efficacy was determined by means of cell culture models in A-253 cells.
Physicochemical properties of nanoparticles achieved by nanoprecipitation from ethanolic solutions were superior to those obtained from a method based upon glycofurol. Nanoencapsulation of temoporfin into the matrix significantly reduced toxicity of this compound, while the efficacy was maintained. The release profiles assured a sustained release at the site of action. Finally, the transfer to continuous flow technology was achieved.
By adjusting all process parameters, a potent formulation for application in the GI tract was obtained. The essential steps of process development and scale-up were part of this formulation development.
纳米级药物递送装置的工业化生产仍是纳米药物商业化的一个障碍。本研究包括开发用于光动力疗法口服应用的纳米颗粒，根据选定的产品规格进行优化，并转化为连续流工艺。
通过在有无聚乙二醇400氢化蓖麻油存在的情况下对Eudragit® RS 100进行纳米沉淀来制备聚合物纳米颗粒。将光敏剂替莫泊芬封装到这些载体装置中。通过实验设计方法优化工艺参数，并使用微反应器技术制造具有最佳特性的纳米颗粒。通过A-253细胞的细胞培养模型测定疗效。
通过从乙醇溶液中进行纳米沉淀获得的纳米颗粒的物理化学性质优于基于聚乙二醇400氢化蓖麻油的方法所获得的性质。将替莫泊芬纳米包封到基质中可显著降低该化合物的毒性，同时保持疗效。释放曲线确保在作用部位持续释放。最后，实现了向连续流技术的转化。
通过调整所有工艺参数，获得了一种用于胃肠道应用的有效制剂。工艺开发和放大的关键步骤是该制剂开发的一部分。
