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

Kazuaki Taguchi, Mai Hashimoto, Shigeru Ogaki, Hiroshi Watanabe, Shinji Takeoka, Yasuo Ikeda, Makoto Handa, Masaki Otagiri, Toru Maruyama

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Adenosine diphosphate (ADP)-encapsulated liposomes coated with a fibrinogen γ-chain dodecapeptide [H12 (dodecapeptide (<sup>400</sup>HHLGGAKQAGDV<sup>411</sup>))-(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.

Original languageEnglish
Pages (from-to)3084-3091
Number of pages8
JournalJournal of Pharmaceutical Sciences
Volume104
Issue number9
DOIs
Publication statusPublished - 2015 Sep 1

Fingerprint

Liposomes
Thrombocytopenia
Adenosine Diphosphate
Fibrinogen
Blood Platelets
Injections
Pharmaceutical Preparations
Complement Activation
Immunoglobulin M
Half-Life
Lipids

Keywords

  • accelerated blood clearance phenomenon
  • adenosine-diphosphate
  • clearance
  • disposition
  • dodecapeptide
  • liposome
  • pegylation
  • pharmacokinetics
  • platelet substitute
  • thrombocytopenia

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

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. / Taguchi, Kazuaki; Hashimoto, Mai; Ogaki, Shigeru; Watanabe, Hiroshi; Takeoka, Shinji; Ikeda, Yasuo; Handa, Makoto; Otagiri, Masaki; Maruyama, Toru.

In: Journal of Pharmaceutical Sciences, Vol. 104, No. 9, 01.09.2015, p. 3084-3091.

Research output: Contribution to journalArticle

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AU - Taguchi, Kazuaki

AU - Hashimoto, Mai

AU - Ogaki, Shigeru

AU - Watanabe, Hiroshi

AU - Takeoka, Shinji

AU - Ikeda, Yasuo

AU - Handa, Makoto

AU - Otagiri, Masaki

AU - Maruyama, Toru

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AB - Adenosine diphosphate (ADP)-encapsulated liposomes coated with a fibrinogen γ-chain dodecapeptide [H12 (dodecapeptide (400HHLGGAKQAGDV411))-(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.

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