伊布替尼
羟基氯喹
体内
胶质瘤
药物输送
细胞毒性
医学
生物利用度
药理学
化学
癌症研究
内科学
体外
免疫学
白血病
生物
生物化学
2019年冠状病毒病(COVID-19)
传染病(医学专业)
慢性淋巴细胞白血病
有机化学
疾病
生物技术
作者
Zhipeng Yang,Yufan Du,Lei Lei,Xiaonan Xue,Xiaorong Wang,Fan Tong,Yuan Li,Huile Gao
标识
DOI:10.1016/j.ijpharm.2022.122436
摘要
Ibrutinib (IBR) is an oral covalent inhibitor of Bruton's tyrosine kinase (BTK) that has been approved for the treatment of hematological malignancies. It was reported that IBR exhibited great therapeutic potential for glioma. However, the poor water solubility and high hepatic first-pass effect restrict its anti-glioma application. Meanwhile, IBR induces cytoprotective autophagy through Akt/mTOR signaling pathway, thus leading to a compromised antitumor effect. Herein, we aimed to develop a human serum albumin (HSA) based co-delivery system (IBR&HCQ HSA NPs) encapsulating IBR and hydroxychloroquine (HCQ). The bioavailability of IBR was largely improved, and enhanced sensitivity of glioma to IBR was achieved due to inhibition effect of HCQ on IBR-induced pro-survival autophagy. The physicochemical properties of IBR&HCQ HSA NPs were characterized to optimize the formulation. Biodistribution investigation revealed that HSA NPs (20 mg/kg, i.v.) dramatically increased the accumulation of IBR in glioma, which was 5.59 times higher than that of free IBR (100 mg/kg, i.g.). CCK-8 and apoptosis assays demonstrated that IBR&HCQ HSA NPs showed maximal cytotoxicity to C6 cells. In vivo studies indicated that the survival time was significantly prolonged in IBR&HCQ HSA NPs treated mice compared to those treated with IBR HSA NPs. Taken together, the HSA-based drug delivery system of IBR and HCQ opens a new avenue for efficient treatment of glioma.
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