Dual-modified liposome codelivery of doxorubicin and vincristine improve targeting and therapeutic efficacy of glioma

Drug Delivery

Xiangyang Xie¹  Lian Yu²  Xiaoyang Han³  Cuiyan Han⁴  Yang Yang⁵  Fanglin Yu⁵  Zhiping Li⁵  Xingguo Mei⁵  Zhijiang Chen⁶  Yue Zhang⁶  Meifang Zhai⁷ 

[1] Department of Pharmacy, Wuhan General Hospital of the Chinese People’s Liberation Army, Wuhan, PR China;Jiamusi University, Jiamusi, PR China;Outpatient Department of Beijing Space City, Aerospace Systems Divison, PLA Strategic Support Force, Beijing, PR China;School of Pharmacy, Qiqihar Medical University, Qiqihar, PR Chin;State key Laboratory of Toxicology and Medical Countermeasure, Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, PR China;State key Laboratory of Toxicology and Medical Countermeasure, Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, PR China;Hubei University of Science and Technology, Xianning, PR China;State key Laboratory of Toxicology and Medical Countermeasure, Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, PR China;Jiamusi University, Jiamusi, PR China;

关键词: T7 peptide;    A7R peptide;    brain targeted drug delivery;    glioma;    doxorubicin;    vincristine;   

DOI  :  10.1080/10717544.2017.1344334

来源: Taylor & Francis

【 摘 要 】

Therapeutic outcome for the treatment of glioma was often limited due to drug resistance and low permeability of drug across the multiple physiological barriers, including the blood-brain barrier (BBB), and the blood-tumor barrier (BTB). In order to overcome these hurdles, we designed T7 and DA7R dual peptides-modified liposomes (abbreviated as T7/DA7R-LS) to efficiently co-delivery doxorubicin (DOX) and vincristine (VCR) to glioma in this study. T7 is a seven-peptide ligand of transferrin receptors (TfR) capable of circumventing the BBB and then targeting glioma. DA7R is a d-peptide ligand of vascular endothelial growth factor receptor 2 (VEGFR 2) overexpressed on angiogenesis, presenting excellent glioma-homing property. By combining the dual-targeting delivery effect, the dual-modified liposomes displayed higher glioma localization than that of single ligand-modified liposomes or free drug. After loading with DOX and VCR, T7/DA7R-LS showed the most favorable antiglioma effect in vivo. In conclusion, this dual-targeting, co-delivery strategy provides a potential method for improving brain drug delivery and antiglioma treatment efficacy.

【 授权许可】

CC BY