Effect of γ-cyclodextrin derivative complexation on the physicochemical properties and antimicrobial activity of hinokitiol

Abstract

The aim of this study was to evaluate the physicochemical properties of solid dispersion on mixtures of hinokitiol (HT) and γ-cyclodextrin (γ-CD) and of HT and (2-hydroxypropyl)-γ-cyclodextrin (HP-γ-CD). Differential scanning calorimetry revealed that coground HT/γ-CD at a molar ratio of 1:1 and HT and HP-γ-CD at molar ratios of 1:1 and 1:2 lacked an endothermic peak due to melting of HT crystals. Powder x-ray diffraction revealed that HT crystal showed a halo pattern respectively, by mixing and grinding of the CDs and HT. Thus, coground HT/γ-CD and HT/HP-γ-CD at a molar ratio of 1:1 had molecular interaction. Assessment of dissolution revealed that ground mixtures had improved dissolution of HT compared to HT crystals, ground HT alone, and physical mixtures containing HT. 1H-1H NOESY NMR suggested that the 7-membered ring and isopropyl group of HT were located within the cavity of γ-CD and HP-γ-CD. The antimicrobial tests indicated that ground mixtures exhibited a minimum inhibitory concentration (MIC) of 20 μg/mL against Bacillus subtilis, 40 μg/mL against Staphylococcus aureus, and 20 μg/mL against Escherichia coli. GMs were found to have 4 times more antimicrobial activity than HT crystals. Ground mixtures also exhibited MIC of 160 μg/mL against Pseudomonas aeruginosa and they were found to 2 times more antimicrobial activity than HT crystals. Improvement in antimicrobial activity with the formation of inclusion complexes is presumably due to increase the solubility of HT as a result of the formation of HT/CD inclusion complexes.