Development of Intravenous Formulation of a Novel Multikinase Inhibitor for Treating Cancer Based on 2-Hydroxypropyl-β-Cyclodextrin Inclusion Complex

Small-molecule inhibitors against one or more of tumor-associated targets are probably potential anticanceragents. We have designed and synthesized a novel multi-targeted inhibitor SKLB610 which presented higheranti-cancer efficacy on several human tumors in vitro and in vivo. However, the poor water-solubility would limitits intravenous application in clinic. To overcome the difficulty, the intravenous formulation containing SKLB610 complexed with 2-hydroxypropyl-β-cyclodextrin (SKLB610-HP-beta-CD) was firstly prepared by solvent evaporationtechnique. Then the inclusion complex was characterized by differential scanning calorimetry, X-ray diffractometryand Fourier-Transform infrared spectroscopy, which indicated that a SKLB610 inclusion complex wasconstructed successfully. Finally, the intravenous pharmacokinetics of SKLB610-HP-beta-CD was investigatedin rats in contrast to SKLB610 solution. SKLB610-HP-beta-CD exhibited higher AUC and plasma concentrationof SKLB610, which suggested that SKLB610 inclusion complex might be a potential i.v. formulation of SKLB610 for more efficient cancer treatment.