Biomaterials Advances ( IF 7.9 ) Pub Date : 2021-01-16 , DOI: 10.1016/j.msec.2021.111890 Ceren Kimna , Benjamin Winkeljann , Julia Hoffmeister , Oliver Lieleg
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.
中文翻译:
具有可调粘膜粘附性的基于生物聚合物的纳米颗粒可有效地跨角膜屏障提供治疗剂
为了克服眼睛系统的自然障碍,该障碍限制了治疗活性分子向后眼的局部递送,可以使用纳米级药物载体来改善经角膜药物的运输。迄今为止,已经提出使用粘膜粘附药物载体作为优化药物运输的最有希望的策略。但是,如果药物载体的粘膜粘附性太高,则可能会限制分子/药物载体扩散进入玻璃体。在这项研究中,我们表明调节基于生物聚合物的药物载体颗粒的净电荷不仅会改变其粘膜粘附性,而且还会改变其他重要特性,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更好的药物通过角膜屏障的转运。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特别注意的功能-不仅是眼部给药尝试,而且是所有处理粘膜屏障的药物递送方法。