Histological study on side effects and tumor targeting of a block copolymer micelle on rats

Takanori Kawaguchi, Takashi Honda, Masamichi Nishihara, Tatsuhiro Yamamoto, Masayuki Yokoyama

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)240-246
Number of pages7
JournalJournal of Controlled Release
Volume136
Issue number3
DOIs
Publication statusPublished - Jun 19 2009
Externally publishedYes

Fingerprint

Micelles
Neoplasms
Mononuclear Phagocyte System
Organ Size
Ethylene Glycol
Poisons
Ascites
Aspartic Acid
Intravenous Injections
Capsules
Hepatocellular Carcinoma
Spleen
Lymph Nodes
Bone Marrow
Body Weight
Weights and Measures
Lung
Liver

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Histological study on side effects and tumor targeting of a block copolymer micelle on rats. / Kawaguchi, Takanori; Honda, Takashi; Nishihara, Masamichi; Yamamoto, Tatsuhiro; Yokoyama, Masayuki.

In: Journal of Controlled Release, Vol. 136, No. 3, 19.06.2009, p. 240-246.

Research output: Contribution to journalArticle

Kawaguchi, Takanori ; Honda, Takashi ; Nishihara, Masamichi ; Yamamoto, Tatsuhiro ; Yokoyama, Masayuki. / Histological study on side effects and tumor targeting of a block copolymer micelle on rats. In: Journal of Controlled Release. 2009 ; Vol. 136, No. 3. pp. 240-246.
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