Development and pharmaceutical evaluation of the anticancer Anthrafuran/Cavitron complex, a prototypic parenteral drug formulation

To improve the water solubility of the anticancer drug candidate LCTA-2034 (A1), we investigated the formation of complexes of this anthrax[2,3-b]furan congener with the solubilizing 2-hydroxypropyl derivative of beta-cyclodextrin HP-beta CD (Cavitron (R)). The interaction of A1 with HP-beta CD resulted in the inclusion complex A1/HP-beta CD in 1: 1 stoichiometry. The A1/HP-beta CD complex was used to develop a prototype of a lyophilised drug formulation with enhanced (> 10-fold) aqueous solubility than A1 and a long-term stability. The use of HP-beta CD decreased the acute toxicity of A1 by > 30%. The A1/HP-beta CD drug formulation as well as A1 in equal doses (5 x 30 mg/kg) to increase the lifespan by up to 140% for mice with i.p. transplanted P388 leukaemia. Furthermore, the A1/HP-beta CD formulation demonstrated a significant and reliable antitumor efficacy in a P388/ADR drug resistant leukaemia and B16/F10 melanoma, proving a perspective of investigations of toxicology, biodistribution and pharmacokinetics.