Preparation, Solubilization and In vitro Anti-tumour Effect of Water-soluble Betulinic Acid/Oligo(polylvinylamino) Bridged bis(β-cyclodextrin)s Complexes

Abstract

A series of water-soluble betulinic acid complexes of betulinic acid/oligo(diethylenetriamino) bridged bis(β-cyclodextrin) (BA/DT-β-CD), betulinic acid/oligo(triethylenetetramino) bridged bis(β-cyclodextrin) (BA/TT-β-CD) and betulinic acid/oligo(tetraethylenepentamino) bridged bis(β-cyclodextrin) (BA/TP-β-CD) were prepared and characterized. IR, SEM, MS and 1H NMR were used to characterise these complexes. The results show that the two cyclodextrin cavities and tether groups of the aforementioned bis(β-cyclodextrin)s can form a well-organized pseudo cavity to accommodate the branch group of BA, respectively. By UPLC analysis, the water solubility was remarkably increased to approximately 310.97, 144.94 and 75.04 μg mL-1 by the solubilising effects of DT-β-CD, TT-β-CD and TP-β-CD, respectively. Furthermore, the anti-tumour effect against HeLa cell line was tested by MTT assay, and the IC50 values of BA in BA/DT-β-CD complex water solutions are 103.89 ± 5.12 μmol L-1, which possess an obvious antiproliferative activity against HeLa cell line.