Thông tin chung
  English
  Đề tài NC khoa học
  Bài báo, báo cáo khoa học
  Hướng dẫn Sau đại học
  Sách và giáo trình
  Các học phần và môn giảng dạy
  Giải thưởng khoa học, Phát minh, sáng chế
  Khen thưởng
  Thông tin khác
  Tài liệu tham khảo
  Hiệu chỉnh
 
Số người truy cập: 106,953,140

 Enhanced antitumour effect for hepatocellular carcinoma in the advanced stage using a cyclodextrin-sorafenib-chaperoned inclusion complex
Tác giả hoặc Nhóm tác giả: Chiuyen Phan, Ziyang Zheng, Jianwei Wang, Qiwen Wang, Xiurong Hu,
Guping Tang and Hongzhen Bai
Nơi đăng: Biomaterials Science (SCIE, Q1, IF: 6.843 - 2021); Số: 10;Từ->đến trang: 1039-1050;Năm: 2019
Lĩnh vực: Y - Dược; Loại: Bài báo khoa học; Thể loại: Quốc tế
TÓM TẮT
ABSTRACT
Hepatocellular carcinoma (HCC) is a hypervascular tumour characterized by tumour-driven neovascularization. The degrees of blood oxygen saturation (DBOS), microvessel density (MVD) and tumour size (TS) are indicators in identifying the development stage of HCC. Herein, we proposed an HCC staging model using HepG2 tumour-bearing mice based on DBOS, MVD and TS. According to the patterns of these three criteria, HCC was classified into four stages: early, intermediate, advanced and end stages. The advanced stage was characterized by MVD of 50–90 (number per mm2), DBOS of 12–16% and TS of 250–600 mm3, which poses a critical challenge in HCC therapy. In order to efficiently control and treat HCC in the advanced stage, we developed a cyclodextrin (CD)-based chaperoned inclusion complex using Sorafenib (Sor), β-CD and γ-CD (SCD) via the co-crystallization method. The structural study manifested that CDs could encapsulate Sor with the hydrophobic cavities at a 1 : 1 stoichiometry ratio. The crystallographic analysis indicated that Sor-β-CD presented a diagonal stacking pattern, while Sor-γ-CD
possessed a channel-type structure. The resultant chaperoned inclusion complexes significantly improved the solubility, dissolution rate and drug release of Sor, leading to superior pharmacokinetics, biodistribution and biosafety through oral administration. The antitumour effect was then evaluated on a mouse model with advanced HCC through oral administration and intratumour injection. The treatment involving the oral administration of SCDs showed a promising therapeutic effect on advanced HCC, which efficiently blocked angiogenesis and inhibited tumour progression. For the treatments using intratumour injections, only Sor-γ-CD exhibited a satisfactory anti-tumour effect with reduction in TS, MVD and DBOS. The enhanced therapeutic performance of Sor-γ-CD was attributed to its channel-type structure, which had an impact on the dissociation and release of the drug. Thus, Sor-γ-CD can be used as a potential prodrug for clinical medicine and basic research to treat HCC.
© Đại học Đà Nẵng
 
 
Địa chỉ: 41 Lê Duẩn Thành phố Đà Nẵng
Điện thoại: (84) 0236 3822 041 ; Email: dhdn@ac.udn.vn