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An optimized molecular inclusion complex of diferuloylmethane: enhanced physical properties and biological activity

Authors Tan Q, Li Y, Wu J, Mei H, Zhao C, Zhang J

Received 27 July 2012

Accepted for publication 31 August 2012

Published 9 October 2012 Volume 2012:7 Pages 5385—5393

DOI https://doi.org/10.2147/IJN.S36404

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Qunyou Tan,1,* Yi Li,2–4,* Jianyong Wu,2,* Hu Mei,5 Chunjing Zhao,3 Jingqing Zhang2

1Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 2Medicine Engineering Research Center, Chongqing Key Laboratory of Biochemical and Molecular Pharmacology, Chongqing Medical University, 3School of Pharmacy, Second Affiliated Hospital, Chongqing Medical University, 4School of Pharmacy, The First People’s Hospital of Chongqing, 5College of Bioengineering, Chongqing University, Chongqing, People’s Republic of China

*These authors contributed equally to this work

Objective: The purpose of this study was to explore and evaluate the enhanced physical properties and biological activity of a molecular inclusion complex (MICDH) comprising diferuloylmethane (DFM) and hydroxypropyl-β-cyclodextrin.
Methods: The preparation conditions of MICDH were optimized using an orthogonal experimental design. The solubility, in vitro release and model fitting, microscopic morphology, molecular structure simulation, anti-lung cancer activity, and action mechanism of MICDH were evaluated.
Results: The solubility of DFM was improved 4400-fold upon complexation with hydroxypropyl-β-cyclodextrin. The release rate of DFM was significantly higher from MICDH than from free DFM. MICDH exhibited higher antitumor activity against human lung adenocarcinoma A549 cells than free DFM. More cells were arrested in the S/G2 phase of the cell cycle or were induced to undergo apoptosis when treated with MICDH than when treated with free DFM. Furthermore, increased reactive oxygen species and intracellular calcium ion levels and decreased mitochondrial membrane potential were observed in cells treated with MICDH.
Conclusion: MICDH markedly improved the physical properties and antitumor activity of DFM. MICDH may prove to be a preferred alternative to free DFM as a formulation for DFM delivery in lung cancer treatment.

Keywords: biological properties, action mechanism, hydroxypropyl-β-cyclodextrin, antitumor activity

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