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. Issue 9 (9th March 2015)

• Record Type: Journal Article
• Authors: Taguchi, Kazuaki; Hashimoto, Mai; Ogaki, Shigeru; Watanabe, Hiroshi; Takeoka, Shinji; Ikeda, Yasuo; Handa, Makoto; Otagiri, Masaki; Maruyama, Toru; Donovan, Maureen D.; Langguth, Peter; Polli, James E.; Tamai, Ikumi; Vig, Balvinder; Yu, Lawrence X.
• Is Part Of: Journal of pharmaceutical sciences. Volume 104:Issue 9(2015:Sep.)
• Page Start: 3084
• Page End: 3091
• Publication Date: 2015-03-09
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.24418
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3084–3091, 2015</p> </abstract>