Ratiometric delivery of two therapeutic candidates with inherently dissimilar physicochemical property through pH-sensitive core–shell nanoparticles targeting the heterogeneous tumor cells of glioma

Drug Delivery

Meng-Ting Lin¹  Bing-Hui Jin¹  Qing Yao¹  De-Li ZhuGe¹  Qun-Yan Zhu¹  Ying-Zheng Zhao¹  Bi-Xin Shen¹  He-Lin Xu¹  Zi-Liang Fan¹  Meng-Qi Tong¹  Yasin Sohawon² 

[1] Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, China;School of International Studies, Wenzhou Medical University, Wenzhou City, China;First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Chin;

关键词: Ratiometric delivery;    dissimilar pharmacokinetics;    combination therapy;    heterogeneity;    targeting;   

DOI  :  10.1080/10717544.2018.1474974

来源: publisher

【 摘 要 】

Currently, combination drug therapy is one of the most effective approaches to glioma treatment. However, due to the inherent dissimilar pharmacokinetics of individual drugs and blood brain barriers, it was difficult for the concomitant drugs to simultaneously be delivered to glioma in an optimal dose ratio manner. Herein, a cationic micellar core (Cur-M) was first prepared from d-α-tocopherol-grafted-ε-polylysine polymer to encapsulate the hydrophobic curcumin, followed by dopamine-modified-poly-γ-glutamic acid polymer further deposited on its surface as a anion shell through pH-sensitive linkage to encapsulate the hydrophilic doxorubicin (DOX) hydrochloride. By controlling the combinational Cur/DOX molar ratio at 3:1, a pH-sensitive core–shell nanoparticle (PDCP-NP) was constructed to simultaneously target the cancer stem cells (CSCs) and the differentiated tumor cells. PDCP-NP exhibited a dynamic diameter of 160.8 nm and a zeta-potential of –30.5 mV, while its core–shell structure was further confirmed by XPS and TEM. The ratiometric delivery capability of PDCP-NP was confirmed by in vitro and in vivo studies, in comparison with the cocktail Cur/DOX solution. Meanwhile, the percentage of CSCs in tumors was significantly decreased from 4.16% to 0.95% after treatment with PDCP-NP. Overall, PDCP-NP may be a promising carrier for the combination therapy with drug candidates having dissimilar physicochemical properties.

【 授权许可】

CC BY