title: Effect of Repeated Injections of Adenosine Diphosphate-Encapsulated Liposomes Coated with a Fibrinogen γ-Chain Dodecapeptide Developed as a Synthetic Platelet Substitute on Accelerated Blood Clearance in a Healthy and an Anticancer Drug-Induced Thrombocytopenia Rat Model.
abstract: Adenosine diphosphate (ADP)-encapsulated liposomes coated with a fibrinogen γ-chain dodecapeptide [H12 (dodecapeptide ((400) HHLGGAKQAGDV(411) ))-(ADP)-liposome] is a synthetic platelet substitute, in which the surface is covered with polyethylene glycol (PEG). It has been reported that repeated injections of PEGylated liposomes induce an accelerated blood clearance (ABC) phenomenon, which involves a loss in the long-circulation half-life of the material when administered repeatedly to the same animals. The objective of this study was to determine whether the ABC phenomenon was induced by repeated injections of H12-(ADP)-liposome in healthy and anticancer drug-induced thrombocytopenia model rats. The findings show that the ABC phenomenon was induced by healthy rats that were repeatedly injected with H12-(ADP)-liposomes at the interval of 5 days at a dose of 10 mg lipids/kg. The ABC phenomenon involves the production of anti-H12-(ADP)-liposome immunoglobulin M (IgM) and complement activation. On the other hand, when thrombocytopenia model rats were repeatedly injected with H12-(ADP)-liposomes under the same conditions, no ABC phenomenon, nor was any suppression of anti-H12-(ADP)-liposome IgM-mediated complement activation observed. We thus conclude that the repeated injection of H12-(ADP)-liposome treatment in rat model with anticancer drug-induced thrombocytopenia did not induce the ABC phenomenon.
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, Nishi-ku, Kumamoto, 862-0082, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Chuo-ku, Kumamoto, 862-0973, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Chuo-ku, Kumamoto, 862-0973, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ogaki
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Chuo-ku, Kumamoto, 862-0973, Japan.|Center for Clinical Pharmaceutical Sciences, Kumamoto University, Chuo-ku, Kumamoto, 862-0973, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Shinjuku-ku, Tokyo, 162-8480, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Takeoka
authors.affiliation: Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Shinjuku-ku, Tokyo, 162-8480, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Center for Transfusion Medicine and Cell Therapy, Keio University, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Handa
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, Nishi-ku, Kumamoto, 862-0082, Japan.|Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Chuo-ku, Kumamoto, 862-0973, Japan.|DDS Research Institute, Sojo University, Nishi-ku, Kumamoto, 862-0082, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Chuo-ku, Kumamoto, 862-0973, Japan.|Center for Clinical Pharmaceutical Sciences, Kumamoto University, Chuo-ku, Kumamoto, 862-0973, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
mesh_terms: D000244:Adenosine Diphosphate / Q000008:administration & dosage*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D001802:Blood Substitutes / Q000008:administration & dosage*; D005340:Fibrinogen / Q000008:administration & dosage*; D006207:Half-Life; D007075:Immunoglobulin M / Q000378:metabolism; D007267:Injections / Q000379:methods; D008081:Liposomes / Q000008:administration & dosage*; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D001802:Blood Substitutes; D007075:Immunoglobulin M; D008081:Liposomes; C027539:fibrinopeptides gamma; D011092:Polyethylene Glycols; D000244:Adenosine Diphosphate; D005340:Fibrinogen
keywords: accelerated blood clearance phenomenon; adenosine-diphosphate; clearance; disposition; dodecapeptide; liposome; pegylation; pharmacokinetics; platelet substitute; thrombocytopenia