RT Journal Article
SR Electronic
T1 Complexation of Albendazole with Hydroxypropyl-β-Cyclodextrin Significantly Improves its Pharmacokinetic Profile, Cell Cytotoxicity and Antitumor Efficacy in Nude Mice
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3659
OP 3666
VO 32
IS 9
A1 ANAHID EHTEDA
A1 PETER GALETTIS
A1 STEPHANIE WAI LING CHU
A1 KRISHNA PILLAI
A1 DAVID L. MORRIS
YR 2012
UL http://ar.iiarjournals.org/content/32/9/3659.abstract
AB Background: Albendazole (ABZ) is a microtubule depolymerizing agent with a remarkable activity against a variety of tumor cells in vitro and in vivo. However, the lack of water solubility limits its application. Therefore, the aim of this study was to formulate ABZ with acetic acid/2-hydroxypropyl-β-cyclodextrin (HPβCD) with the view of improving its aqueous solubility and therefore, its antitumor efficacy. Materials and Methods: ABZ was dissolved in acetic acid and 25% HPβCD (w/v). Mice received a single dose of ABZ/HPβCD or a conventional suspension in hydroxypropyl methyl cellulose (HPMC) over 24 h and the concentration of ABZ and its metabolites in plasma were measured by HPLC. The antitumor efficacy of the two formulations were then evaluated and compared in nude mice bearing HCT-116 colorectal cancer xenografts. Results: Ionization with acetic acid together with complexation with hydroxylpropyl-β-cyclodextrin (HPβCD) dramatically improved the solubility of ABZ. The area under the curve (AUC) of ABZ and its active metabolite, ABZ sulfoxide (ABZSO) were approximately 2.3- and 7.3-folds higher in mice that received ABZ/HPβCD in comparison with animals that were treated with ABZ/HPMC. Additionally, the peak plasma concentration (Cmax) of ABZSO was nearly 18-times higher in mice that received ABZ/HPβCD. Furthermore, a significant delay in tumor growth that led to longer survival in mice was observed in the ABZ/HPβCD-treated group as compared to the ABZ/HPMC group. Conclusion: These findings demonstrate that the combination of acetic acid and HPβCD significantly improves the solubility, pharmacokinetic profile and antitumor efficacy of ABZ. This newly-developed formulation of ABZ may be suitable for parenteral administration.