Co-delivery of ibrutinib and hydroxychloroquine by albumin nanoparticles for enhanced chemotherapy of glioma

被引：23

作者：

Yang, Zhihang ^{[1
]}

Du, Yufan ^{[1
]}

Lei, Lei ^{[1
]}

Xia, Xue ^{[1
]}

Wang, Xiaorong ^{[1
]}

Tong, Fan ^{[1
]}

Li, Yuan ^{[2
]}

Gao, Huile ^{[1
]}

机构：

[1] Sichuan Univ, Sichuan Res Ctr Drug Precis Ind Technol, Educ Minist, Key Lab Drug Targeting & Drug Delivery Syst,West, Chengdu 610064, Peoples R China

[2] Peking Univ Third Hosp, Gynecol & Obstet Dept, Beijing 100191, Peoples R China

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2023年 / 630卷

基金：

北京市自然科学基金;

关键词：

Ibrutinib; Albumin nanoparticles; Glioma; Autophagy inhibition; Combined therapy; ADJUVANT TEMOZOLOMIDE; TARGETING BTK; AUTOPHAGY;

D O I：

10.1016/j.ijpharm.2022.122436

中图分类号：

R9 [药学];

学科分类号：

1007 ;

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.

引用

页数：11