title: Novel irinotecan-loaded liposome using phytic acid with high therapeutic efficacy for colon tumors.
abstract: Phytic acid (IP-6) is a polyphosphorylated carbohydrate with antitumor activity for many kinds of tumors. In this study, we developed a novel method of loading irinotecan (CPT-11) into liposomes using IP-6, and evaluated its antitumor effect on colon tumors in vivo. Liposomal CPT-11 was prepared by loading CPT-11 to distearoylphosphatidylcholine/cholesterol/methoxy-poly(ethyleneglycol)-distearylphosphatidylethanolamine liposomes prepared in IP-6 solution, CuSO(4) solution and citrate buffer, respectively (IP6-, Cu- and Cit-L). CPT-11 loading efficiency for IP6-L (90-100%) was higher than that for Cit-L (less than 40%), and similar to Cu-L when CPT-11 to total lipid weight ratio was increased from 0.2 to 0.6. Plasma elimination and biodistribution of liposomal CPT-11 and its metabolite SN-38 were measured after intravenous administration. IP6-L following i.v. injection showed 1.3- and 1.7-fold higher plasma area under the curves of CPT-11 and SN-38, respectively, than Cu-L. Finally, therapeutic activity was determined in mouse Colon 26 and human COLO 320DM tumor xenografts in mice. IP6-L significantly exhibited superior anticancer activity to Cu-L and free CPT-11 in Colon 26 tumor. Using IP-6 as a drug-trapping agent in liposome, IP6-L improved CPT-11 pharmacokinetics and increased antitumor activity in colon tumors.
authors.affiliation: Department of Fine Drug Targeting Research, Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan. yhattori@hoshi.ac.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hattori
authors.forename: Li
authors.initials: L
authors.lastname: Shi
authors.forename: Wuxiao
authors.initials: W
authors.lastname: Ding
authors.forename: Kimiko
authors.initials: K
authors.lastname: Koga
authors.forename: Kumi
authors.initials: K
authors.lastname: Kawano
authors.forename: Motoki
authors.initials: M
authors.lastname: Hakoshima
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maitani