Inclusion complexes of paclitaxel and oligo(ethylenediamino) bridged bis(β-cyclodextrin)s: solubilization and antitumor activity Original Research Article

The inclusion complexation behavior of paclitaxel with a series of oligo(ethylenediamino) bridged bis(β-cyclodextrin)s possessing bridge chains in different length (1–4) has been investigated in order to improve the water solubility of paclitaxel. It is found that only the long-tethered bis(β-cyclodextrin)s 1 and 2 can form the inclusion complexes with paclitaxel, which are characterized by NMR, SEM, XRD, FT-IR, TG–DTA, DSC, and microcalorimetry technology. The results obtained show that bis(β-cyclodextrin)s 1 and 2 are able to solubilize paclitaxel to high levels up to 2 and 0.9 mg/mL, respectively. The high complex stability of bis(β-cyclodextrin) 1 and paclitaxel is discussed from thermodynamic viewpoint. Furthermore, the cytotoxicity of these complexes assessed using a human erythroleukemia K562 cell line indicates that the IC50 value of 1/paclitaxel complex is 6.0 × 10−10 mol/dm3 (calculated as paclitaxel molar concentration), which means that the antitumor activity of 1/paclitaxel complex is better than that of parent paclitaxel (IC50 value 9.8 × 10−10 mol/dm3). This high antitumor activity, along with the satisfactory water solubility and high thermal stability of the 1/paclitaxel complex, will be potentially useful for its clinical application as a highly effective antitumor drug.