Abstract
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.
Similar content being viewed by others
References
Shevchuk, I., Chekulayev, V., Moan, J., Berg, K.: Effects of the inhibitors of energy metabolism, lonidamine and levamisole, on 5-aminolevulinic-acid-induced photochemotherapy. Int. J. Cancer 67, 791–799 (1996)
Pratesi, G., De Cesare, M., Zumino, F.: Efficacy of lonidamine combined with different DNA-damaging agents in the treatment of the MX-1 tumor xenograft. Cancer Chemother. Pharmacol. 38, 123–128 (1996)
Dogliotti, L., Berrtui, A., Buniva, T., Zola, P., Bau, M.G., Farris, A., Sarobba, M.G., Bottini, A., Alquati, P., Deltetto, F., Gosso, P., Monzeglio, C., Moro, G., Sussio, M., Perroni, D.: Lonidamine induces apoptosis in drug-resistant cells independently of the p53 gene. J. Clin. Oncol. 14, 1165–1172 (1996)
Zaniboni, A., Meriggi, F., Alghisi, A., Mutti, S., Distefano, L., Bettini, L., Simoncini E., Marpicati, P., Montini E.: Mitomycin-C and lonidamine as second-line therapy for colorectal cancer: a phase II study. Cancer J 81, 435–437 (1995)
Gardin, G.: Lonidamine plus epirubicin and cyclophosphamide in advanced breast cancer. Eur. J. Cancer Part A 32A, 176–177 (1996)
Fanciulli, M.: Lonidamine: efficacy and safety in clinical trials for the treatment of solid tumors. Oncol. Res. 8, 111–120 (1996)
Gadducci, A., Brunetti, I., Muttini, M.P., Fanucchi, A., Dargenio, F., Giannessi, P.G., Conte, P.F.: Epidoxorubicin and lonidamine in refractory or recurrent epithelial ovarian cancer. Eur J Cancer 30(2), 1432–1435 (1994)
Lahiani-Skiba, M., Boulet, Y., Youm, I., Bounoure, F., Vérite, Ph., Arnaud, Ph., Skiba, M.: Improvement in the water solubility and stability of 4ASA by the use of cyclodextrins. J. Incl. Phenom. Macrocycl. Chem. 57, 211–217 (2007)
Palmieri, G.F., Wehrlé, P., Martelli, S.: Interactions between Lonidamine and beta-or hydroxypropyl-beta-cyclodextrin. Drug. Dev. Ind. Pharm 24(7), 653–660 (1998)
Higuchi, T., Connors, K.A.: Preparation and evaluation of ketoconazole-[beta]-cyclodextrin. Anal. Chem. Instrum. 4, 117–212 (1965)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lahiani-Skiba, M., Bounoure, F., Fessi, H. et al. Effect of cyclodextrins on lonidamine release and in-vitro cytotoxicity. J Incl Phenom Macrocycl Chem 69, 481–485 (2011). https://doi.org/10.1007/s10847-010-9872-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10847-010-9872-7