Tumor-targeting intravenous lipid emulsion of paclitaxel:Characteristics,stability,toxicity,and toxicokinetics  

作　　者：Jun Ye Lin Li Jiye Yin Hongliang Wang Renjie Li Yanfang Yang Yongbiao Guan Xuejun Xia Yuling Liu 

机构地区：[1]State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,100050,China [2]Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,100050,China [3]National Beijing Center for Drug Safety Evaluation and Research,Beijing Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing,100850,China

出　　处：《Journal of Pharmaceutical Analysis》2022年第6期901-912,共12页药物分析学报（英文版）

基　　金：supported by the National Science and Technology Major Project of China(Grant No.:2018ZX09711001);Beijing Nova Program(Grant No.:Z211100002121127);Beijing Natural Science Foundation(Grant No.:L212059);Fundamental Research Funds for the Central Universities(Grant No.:3332021101);CAMS Innovation Fund for Medical Sciences(CIFMS,Grant No.:2022-I2M-JB-011).

摘　　要：Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and systemic safety profiles have not yet been reported.Here we outline the development of a PTXloaded tumor-targeting intravenous lipid emulsion(PTX Emul)and describe its characteristics,colloidal stability,and systemic safety profiles in terms of acute toxicity,long-term toxicity,and toxicokinetics.We also compare PTX Emul with conventional PTX injection.Results showed that PTX Emul exhibited an ideal average particle size(approximately 160 nm)with narrow size distribution and robust colloidal stability under different conditions.Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential.In addition,where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs,including the decreased AUC and increased plasma clearance and volume of distribution,PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose,moderate body weight change,decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose.A fundamental understanding of the systemic safety profiles,high tumor-targeting efficiency,and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.

关 键 词：Nanodrug delivery systems Lipid emulsion PACLITAXEL Colloidal Stability TOXICOKINETICS 

分 类 号：R318.08[医药卫生—生物医学工程]