Preparation and characterization of inclusion complexes of antitumor camptothecin with cucurbit[n = 7, 8]urils

The slightly water-soluble anticancer drug camptothecin (CPT) and its inclusion complexes with cucurbit[n = 7, 8]uril (Q[n] (n = 7, 8)) were investigated. The formation of 1:2 complexes with Q[n] (n = 7, 8) in aqueous solution was confirmed by fluorescence spectroscopy and the apparent stability constants were determined to be higher than 3.01 × 1012 L2/mol2. The solid inclusion complexes of CPT and Q[n] (n = 7, 8) were also prepared by the co-evaporation method and characterized by Fourier transformation-infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction. Aqueous solubility and dissolution studies indicate that the complexes exhibited significantly increased dissolution rates compared with the pure drug and physical mixtures. The potential of Q[7] or Q[8] for stabilizing lactone modality of CPT was investigated by the High Performance Liquid Chromatography (HPLC) method. The results reveal more than 63% CPT lactone form (active form) in CPT-Q[7] or Q[8] complexes compared to only 36% CPT lactone form in the absence of Q[7] or Q[8] after being incubated in the phosphate buffer solution (pH 7.4 at 37°C) for 5 h.