Chitosan-based Intelligent Charge-reversed System for High Efficiency Delivery of Paclitaxel
MA Yu-feng LV Pi-ping YUE Zhan-guo WEI Wei MA Guang-hui YU Rong
Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University . State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences . State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences Institute of Process Engineering, Chinese Academy of Sciences State Key Lab. Biochem. Eng., Inst. Process Eng., Chinese Academy of Sciences Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University
Abstract：After modification by tris(2-aminoethyl) amine (TAEA) and 2,3-dimethylmaleic anhydride (DMMA), chitosan nanoparticles (CNP) were endowed with intelligent charge-reversal ability. The fabricated system (CNP-TAEA-DMMA- nanoparticles) was then loaded with insoluble anticancer drug paclitaxel (PTX), and the drug delivery efficiency was tested in vivo. The results showed that PTX-CNP-TAEA-DMMA- nanoparticles were negatively charged (-11 mV) at normal tissue circumstance (pH 7.4) and rarely internalized by J774.1 cells, exhibiting stealth effect to macrophages. Once reaching the cancer site, those nanoparticles could intelligently transform to positive charge (+5 mV) by the low-pH microenvironment in tumor tissue, which could improve tumor cell uptake and accordingly increase the drug concentration at the lesion site. Compared with commercial PTX formulation, the nanoparticles possessed superior biocompatibility and better cytotoxicity (the value of half inhibitory concentration was decreased to 4.09 from 11.3 mg/mL), holding a great potential as efficient anti-cancer drug carrier.