Preparation of curcumin self-micelle solid dispersion with enhanced bioavailability and cytotoxic activity by mechanochemistry

Drug Delivery

Nikolay E. Polyakov¹  Yulia S. Chistyachenko²  Alexandr V. Dushkin³  Mikhail V. Khvostov⁴  Tatjana G. Tolstikova⁴  Tatjana S. Frolova⁵  Qihong Zhang⁶  Weike Su⁷ 

[1] Institute of Chemical Kinetics and Combustion, Novosibirsk, Russia;Institute of Solid State Chemistry and Mechanochemistry, Novosibirsk, Russia;Institute of Solid State Chemistry and Mechanochemistry, Novosibirsk, Russia;Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, PR Chin;N.N. Vorozhtsov Institute of Organic Chemistry SB RAS, Novosibirsk, Russia;Novosibirsk State University, Novosibirsk, Russia;N.N. Vorozhtsov Institute of Organic Chemistry SB RAS, Novosibirsk, Russia;Novosibirsk State University, Novosibirsk, Russia;Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia;National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, PR China;National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, PR China;Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, PR Chin;

关键词: Mechanical ball milling;    solid dispersion;    curcumin;    self-micelle;    cytotoxic activity;    bioavailability;   

DOI  :  10.1080/10717544.2017.1422298

来源: publisher

【 摘 要 】

An amorphous solid dispersion (SD) of curcumin (Cur) with disodium glycyrrhizin (Na2GA) was prepared by mechanical ball milling. Curcumin loaded micelles were self-formed by Na2GA when SD dissolved in water. The physical properties of Cur SD in solid state were characterized by differential scanning calorimetry, X-ray diffraction studies, and scanning electron microscope. The characteristics of the sample solutions were analyzed by reverse phase HPLC, UV–visible spectroscopy, 1H NMR spectroscopy, gel permeation LC, and transmission electron microscopy. In vitro cytotoxic tests demonstrated that Cur SD induced higher cytotoxicity against glioblastoma U-87 MG cells than free Cur. Besides, an improvement of membrane permeability of Cur SD was confirmed by parallel artificial membrane permeability assay. Further pharmacokinetic study of this SD formulation in rat showed a significant ∼19-fold increase of bioavailability as comparing to free Cur. Thus, Cur SD provide a more potent and efficacious formulation for Cur oral delivery.

【 授权许可】

CC BY