School of Chemical Engineering, Sichuan University, Chengdu 610065, Sichuan, People's Republic of China.
School of Chemical Engineering, Sichuan University, Chengdu 610065, Sichuan, People's Republic of China.
J Pharm Sci. 2020 Feb;109(2):1136-1144. doi: 10.1016/j.xphs.2019.10.007. Epub 2019 Oct 10.
In this study, a novel Bruton's tyrosine kinase inhibitor, ibrutinib, was loaded into chitosan/sulfobutylether-β-cyclodextrin nanoparticles (NPs). NPs have gained high loading efficiency for the hydrophobic drug due to the inclusion of cyclodextrin. Ibrutinib-loaded NPs with an average diameter of 277.9 nm and ζ-potential of +19.1 mV were obtained after regulating several influencing factors. Electrostatic reaction between mucin and NPs indicated that the NPs had a mucoadhesive property. Kinase catalytic phosphorylation was monitored by capillary zone electrophoresis and found that chitosan/sulfobutylether-β-cyclodextrin NPs did not weaken ibrutinib activity on the target kinase. In vitro drug release studies revealed that ibrutinib-loaded NPs exhibited a significantly slower gastric-release rate. This study applied a feasible nanocarrier for ibrutinib delivery, and the potential nanoformulation maintains drug activity and shows a sustained release property. These outcomes are helpful for the formulation exploitation of tyrosine kinase inhibitors.
在这项研究中，一种新型布鲁顿酪氨酸激酶抑制剂伊布替尼被载入壳聚糖/磺丁基醚-β-环糊精纳米粒（NPs）中。由于环糊精的包含，NPs 对疏水性药物具有高的载药效率。通过调节几个影响因素，获得了平均直径为 277.9nm 和 ζ-电位为+19.1mV 的伊布替尼载药 NPs。NPs 与粘蛋白之间的静电反应表明 NPs 具有粘膜粘附性。通过毛细管区带电泳监测激酶催化磷酸化，发现壳聚糖/磺丁基醚-β-环糊精 NPs 并未削弱伊布替尼对靶激酶的活性。体外药物释放研究表明，伊布替尼载药 NPs 表现出明显较慢的胃释放速率。本研究应用了一种可行的纳米载体来递送伊布替尼，该潜在的纳米制剂保持了药物的活性并表现出持续释放的特性。这些结果有助于开发酪氨酸激酶抑制剂的制剂。
