Effect of cyclodextrins on lonidamine release and in-vitro cytotoxicity
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The objective of this work was to study the effect of natural, hydroxypropyl and partially methylated cyclodextrins on the solubility of lonidamine and the cytotoxicity of the inclusion complex. The solubility study was conducted according to Higuchi et al. where HP-α-CD, HP-β-CD and HP-γ-CD showed type AL solubility curves indicating the formation of inclusion complexes with molar ratio of 1:1 with lonidamine. However, AP and AN type phase solubility behaviors were observed with PM-CD and α-CD, β-CD and γ-CD, respectively. Solubility enhancement factors and stability constants (K1:1 and K1:2) were calculated from the phase diagrams as appropriate. The characterization of the above inclusion complexes was evaluated using differential scanning calorimetry, Fourier transform infrared, and dissolution. Lonidamine solubility was improved with all tested cyclodextrins and specifically with PM-β-CD (1148 mg/L) where the solubility increased by 380-fold compare to its solubility in water (3 mg/L) leading to a fast dissolution rate of the latter in less than 3 min. In addition, the in-vitro cytotoxicity studies showed a modest increase in the cytotoxicity of lonidamine complex with CD against the human glioblastoma cell line SNB-19. Cyclodextrins could be useful to improve the solubility of lonidamine and hence its bioavailability, which is a drug of interest in the cancer treatment.
KeywordsLonidamine Cyclodextrins Solubility Cytotoxicity Characterization
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