期刊
JOURNAL OF CONTROLLED RELEASE
卷 136, 期 3, 页码 240-246出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2009.02.011
关键词
Polymeric micelle; Pathology; Side effects; Block copolymer; Targeting
资金
- Ministry of Health, Labour and Welfare of Japan
- Program for Promoting the Establishment of Strategic Research Centers
- Special Coordination Funds for Promoting Science and Technology
- Ministry of Education, Culture, Sports, Science, and Technology, Japan
Histological examinations were performed with polymeric micelle-injected rats for evaluations of possible toxicities of polymeric micelle carriers. Weight of major organs as well as body weight of rats was measured after multiple intravenous injections of polymeric micelles forming from poly(ethylene glycol)-b-poly (aspartate) block copolymer. No pathological toxic side effects were observed at two different doses, followed only by activation of the mononuclear phagocyte system (MPS) in the spleen, liver, lung, bone marrow, and lymph node. This finding confirms the absence of - or the very low level of - in vivo toxicity of the polymeric micelle carriers that were reported in previous animal experiments and clinical results. Then, immunohistochemical analyses with a biotinylated polymeric micelle confirmed specific accumulation of the micelle in the MPS. The immunohistochemical analyses also revealed, first, very rapid and specific accumulation of the micelle in the vasculatures of tumor capsule of rat ascites hepatoma AH109A, and second, the micelle's scanty infiltration into tumor parenchyma. This finding suggests a unique tumor-accumulation mechanism that is very different from simple EPR effect-based tumor targeting. (C) 2009 Elsevier B.V. All rights reserved.
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