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
| Autor: | Shigeru Ogaki, Yasuo Ikeda, Shinji Takeoka, Kazuaki Taguchi, Mai Hashimoto, Masaki Otagiri, Makoto Handa, Toru Maruyama, Hiroshi Watanabe |
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| Rok vydání: | 2015 |
| Předmět: |
Blood Platelets
Male Pharmaceutical Science Antineoplastic Agents Pharmacology Fibrinogen Injections Polyethylene Glycols Rats Sprague-Dawley chemistry.chemical_compound Pharmacokinetics Blood Substitutes medicine Animals Platelet Liposome biology business.industry Thrombocytopenia Rats Complement system Adenosine Diphosphate Adenosine diphosphate Immunoglobulin M chemistry Biochemistry Liposomes biology.protein PEGylation business Half-Life medicine.drug |
| Zdroj: | Journal of Pharmaceutical Sciences. 104:3084-3091 |
| ISSN: | 0022-3549 |
| DOI: | 10.1002/jps.24418 |
| Popis: | 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 5days at a dose of 10mg 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 |
| Databáze: | OpenAIRE |
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