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

Qihong Zhang; Nikolay E Polyakov; Yulia S Chistyachenko; Mikhail V Khvostov; Tatjana S Frolova; Tatjana G Tolstikova; Alexandr V Dushkin; Weike Su

doi:10.1080/10717544.2017.1422298

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

Drug Deliv. 2018 Nov;25(1):198-209. doi: 10.1080/10717544.2017.1422298.

Authors

Qihong Zhang¹, Nikolay E Polyakov², Yulia S Chistyachenko³, Mikhail V Khvostov^{4

5}, Tatjana S Frolova^{4

5

6}, Tatjana G Tolstikova^{4

5}, Alexandr V Dushkin^{3

7}, Weike Su^{1

7}

Affiliations

¹ a 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.
² b Institute of Chemical Kinetics and Combustion , Novosibirsk , Russia.
³ c Institute of Solid State Chemistry and Mechanochemistry , Novosibirsk , Russia.
⁴ d N.N. Vorozhtsov Institute of Organic Chemistry SB RAS , Novosibirsk , Russia.
⁵ e Novosibirsk State University , Novosibirsk , Russia.
⁶ f Institute of Cytology and Genetics SB RAS , Novosibirsk , Russia.
⁷ g Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology , Hangzhou , PR China.

Abstract

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.

Keywords: Mechanical ball milling; bioavailability; curcumin; cytotoxic activity; self-micelle; solid dispersion.

MeSH terms

Animals
Biological Availability
Calorimetry, Differential Scanning / methods
Cell Line, Tumor
Chemistry, Pharmaceutical / methods
Curcumin / chemistry*
Curcumin / pharmacokinetics*
Curcumin / pharmacology
Drug Carriers / chemistry
Glioblastoma / drug therapy
Glioblastoma / metabolism
Glycyrrhizic Acid / chemistry
Humans
MCF-7 Cells
Male
Micelles
Particle Size
Permeability
Rats
Rats, Sprague-Dawley
Water / chemistry
X-Ray Diffraction / methods

Substances

Drug Carriers
Micelles
Water
Glycyrrhizic Acid
Curcumin

Grants and funding

We thank International S&T Cooperation Program of China (2013DFR40560) for financial support.