Institute for Particle Technology (iPAT), Technische Universität Braunschweig, 38104 Braunschweig, Germany.
Centre for Pharmaceutical Engineering Research (PVZ), Technische Universität Braunschweig, 38106 Braunschweig, Germany.
Int J Mol Sci. 2019 Sep 22;20(19):4696. doi: 10.3390/ijms20194696.
Niosomes are non-ionic surfactant-based vesicles with high promise for drug delivery applications. They can be rapidly prepared via microfluidics, allowing their reproducible production without the need of a subsequent size reduction step, by controlled mixing of two miscible phases of an organic (lipids dissolved in alcohol) and an aqueous solution in a microchannel. The control of niosome properties and the implementation of more complex functions, however, thus far are largely unknown for this method. Here we investigate microfluidics-based manufacturing of topotecan (TPT)-loaded polyethylene glycolated niosomes (PEGNIO). The flow rate ratio of the organic and aqueous phases was varied and optimized. Furthermore, the surface of TPT-loaded PEGNIO was modified with a tumor homing and penetrating peptide (tLyp-1). The designed nanoparticular drug delivery system composed of PEGNIO-TPT-tLyp-1 was fabricated for the first time via microfluidics in this study. The physicochemical properties were determined through dynamic light scattering (DLS) and zeta potential analysis. In vitro studies of the obtained formulations were performed on human glioblastoma (U87) cells. The results clearly indicated that tLyp-1-functionalized TPT-loaded niosomes could significantly improve anti-glioma treatment.
毫微粒是基于非离子表面活性剂的囊泡，在药物传递应用方面有很大的前景。它们可以通过微流控技术快速制备，通过在微通道中控制两种可混溶相（溶解在酒精中的脂质和水溶液）的混合，可以在无需后续的粒径减小步骤的情况下，可重复地生产毫微粒，而无需后续的粒径减小步骤。然而，到目前为止，对于这种方法，毫微粒的性质控制和更复杂功能的实现在很大程度上是未知的。在这里，我们研究了基于微流控技术的拓扑替康（TPT）负载聚乙二醇化毫微粒（PEGNIO）的制造。改变并优化了有机相和水相的流速比。此外，还对载有 TPT 的 PEGNIO 表面进行了肿瘤归巢和穿透肽（tLyp-1）的修饰。本研究首次通过微流控技术设计了由 PEGNIO-TPT-tLyp-1 组成的纳米药物传递系统。通过动态光散射（DLS）和zeta 电位分析确定了其物理化学性质。对获得的制剂进行了体外研究，研究对象为人神经胶质瘤（U87）细胞。结果清楚地表明，tLyp-1 功能化的 TPT 负载毫微粒能够显著改善抗脑胶质瘤治疗效果。
