Behnke Mira, Klemm Paul, Dahlke Philipp, Shkodra Blerina, Beringer-Siemers Baerbel, Czaplewska Justyna Anna, Stumpf Steffi, Jordan Paul M, Schubert Stephanie, Hoeppener Stephanie, Vollrath Antje, Werz Oliver, Schubert Ulrich S
Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstraße 10, 07743 Jena, Germany.
Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, 07743 Jena, Germany.
Int J Pharm X. 2023 Feb 24;5:100173. doi: 10.1016/j.ijpx.2023.100173. eCollection 2023 Dec.
Dextran-based polymers, such as ethoxy acetalated dextran (Ace-DEX), are increasingly becoming the focus of research as they offer great potential for the development of polymer-based nanoparticles as drug delivery vehicles. Their major advantages are the facile synthesis, straightforward particle preparation and the pH-dependent degradation of the particles that can be fine-tuned by the degree of acetalation of the polymer. In this study we have shown that Ace-DEX can not only compete against the commonly used and FDA-approved polymer poly(lactic--glycolic acid) (PLGA), but even has the potential to outperform it in its encapsulation properties, , for the herein used anti-inflammatory leukotriene biosynthesis inhibitor BRP-187. We used three different methods (microfluidics, batch nanoprecipitation and emulsion solvent evaporation) for the preparation of BRP-187-loaded Ace-DEX nanoparticles to investigate the influence of the formulation technique on the physicochemical properties of the particles. Finally, we evaluated which production method offers the greatest potential for achieving the demands for a successful translation from research into pharmaceutical production by fulfilling the basic requirements, such as reaching a high loading capacity of the particles and excellent reproducibility while being simple and affordable.
基于葡聚糖的聚合物,如乙氧基缩醛化葡聚糖(Ace-DEX),正日益成为研究的焦点,因为它们在开发基于聚合物的纳米颗粒作为药物递送载体方面具有巨大潜力。它们的主要优点是合成简便、颗粒制备直接,以及颗粒的pH依赖性降解可通过聚合物的缩醛化程度进行微调。在本研究中,我们表明Ace-DEX不仅可以与常用的且已获美国食品药品监督管理局(FDA)批准的聚合物聚乳酸-乙醇酸共聚物(PLGA)相竞争,而且对于本文所使用的抗炎白三烯生物合成抑制剂BRP-187,其在包封性能方面甚至有超越PLGA的潜力。我们使用了三种不同方法(微流控法、批量纳米沉淀法和乳液溶剂蒸发法)制备负载BRP-187的Ace-DEX纳米颗粒,以研究制剂技术对颗粒物理化学性质的影响。最后,我们评估了哪种生产方法在满足基本要求(如达到颗粒的高载药量和出色的重现性,同时操作简单且成本低廉)方面,为实现从研究成功转化为药物生产的需求提供了最大潜力。