Kimna Ceren, Winkeljann Benjamin, Hoffmeister Julia, Lieleg Oliver
Department of Mechanical Engineering and Munich School of Bioengineering, Technical University of Munich, Boltzmannstraße 11, 85748 Garching, Germany; Center for Protein Assemblies, Technical University of Munich, Ernst-Otto-Fischer Str. 8, 85748 Garching, Germany.
Department of Mechanical Engineering and Munich School of Bioengineering, Technical University of Munich, Boltzmannstraße 11, 85748 Garching, Germany; Center for Protein Assemblies, Technical University of Munich, Ernst-Otto-Fischer Str. 8, 85748 Garching, Germany.
Mater Sci Eng C Mater Biol Appl. 2021 Feb;121:111890. doi: 10.1016/j.msec.2021.111890. Epub 2021 Jan 16.
To overcome the natural barriers of the ocular system that limit the topical delivery of therapeutically active molecules to the posterior eye, nanoscale drug carriers can be used to improve transcorneal drug transport. So far, using mucoadhesive drug carriers has been put forward as the most promising strategy to optimize drug transport. However, if the mucoadhesivity of a drug carrier is too high, this might limit the diffusive entry of molecules/drug carriers into the vitreous. In this study, we show how modulating the net charge of biopolymer-based drug carrier particles alters not only their mucoadhesivity but also other important properties, e.g., their stability, drug loading capacity and drug release profiles. Compared to simple aqueous solutions of free drug molecules as used in current treatments, nanoparticulate drug carriers with intermediate mucoadhesivity show improved drug transport across the corneal barrier. Therefore, our study shows that mucoadhesion of drug carrier particles is a feature that needs to be considered with great care - not only for ocular delivery attempts but for all drug delivery approaches dealing with mucosal barriers.
为克服眼部系统的天然屏障（这些屏障限制了治疗活性分子向眼后段的局部递送），可使用纳米级药物载体来改善经角膜的药物转运。到目前为止，使用粘膜粘附性药物载体已被提出作为优化药物转运的最有前景的策略。然而，如果药物载体的粘膜粘附性过高，这可能会限制分子/药物载体向玻璃体的扩散性进入。在本研究中，我们展示了调节基于生物聚合物的药物载体颗粒的净电荷如何不仅改变其粘膜粘附性，还改变其他重要特性，例如它们的稳定性、载药量和药物释放曲线。与当前治疗中使用的游离药物分子的简单水溶液相比，具有中等粘膜粘附性的纳米颗粒药物载体显示出改善的药物跨角膜屏障转运。因此，我们的研究表明，药物载体颗粒的粘膜粘附性是一个需要极其谨慎考虑的特性——不仅对于眼部给药尝试，而且对于所有涉及粘膜屏障的药物递送方法都是如此。
