Document Detail

Spatial distribution of intraperitoneally administrated paclitaxel nanoparticles solubilized with poly (2-methacryloxyethyl phosphorylcholine-co n-butyl methacrylate) in peritoneal metastatic nodules.
MedLine Citation:
PMID:  20942868     Owner:  NLM     Status:  MEDLINE    
Intraperitoneal (i.p.) administration of paclitaxel nanoparticles (PTX-30W) prepared by solubulization with the amphiphilic copolymer of 2-methacryloxyethyl phosphorylcholine and n-butyl methacrylate can efficiently suppress the growth of peritoneal metastasis. In this study, we characterized the drug distribution of i.p. injected PTX-30W in peritoneal tumor and liver in a mouse model using MKN45, human gastric cancer cells. Oregon green-conjugated PTX-30W showed perivascular accumulation in MKN45 tumor in the peritoneum at 24 h after intravenous (i.v.) injection; however, the amount of PTX in tumor was markedly less than that in liver. In contrast, a larger amount of PTX accumulated in the peripheral area of disseminated nodules at 1 h after i.p. injection and the area gradually enlarged. The depth of PTX infiltration reached 1 mm from the tumor surface at 48 h after i.p. injection, and the fluorescence intensity was markedly greater than that in liver. Interestingly, i.p. injected PTX preferentially accumulated in relatively hypovascular areas, and many tumor cells in the vicinity of PTX accumulation showed apoptosis. This unique accumulation pattern and lesser washout in hypovascular areas are thought to be attributable to the superior penetrating activity of PTX-30W, and thus, PTX-30W is considered to be highly suitable for i.p. chemotherapy for peritoneal dissemination.
Takao Kamei; Joji Kitayama; Hironori Yamaguchi; Daisuke Soma; Shigenobu Emoto; Tomohiro Konno; Kazuhiko Ishihara; Hironori Ishigami; Shoichi Kaisaki; Hirokazu Nagawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-13
Journal Detail:
Title:  Cancer science     Volume:  102     ISSN:  1349-7006     ISO Abbreviation:  Cancer Sci.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-16     Completed Date:  2011-01-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101168776     Medline TA:  Cancer Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  200-5     Citation Subset:  IM    
Copyright Information:
© 2010 Japanese Cancer Association.
Department of Surgery, Division of Surgical Oncology, University of Tokyo, Tokyo, Japan.
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MeSH Terms
Antineoplastic Agents, Phytogenic / pharmacokinetics*
Cell Line, Tumor
Injections, Intraperitoneal
Liver / metabolism
Methacrylates / chemistry*
Mice, Inbred BALB C
Nanoparticles / administration & dosage*
Paclitaxel / administration & dosage,  pharmacokinetics*
Peritoneal Neoplasms / drug therapy*,  metabolism,  secondary
Phosphorylcholine / analogs & derivatives*,  chemistry
Tissue Distribution
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Methacrylates; 107-73-3/Phosphorylcholine; 125275-25-4/poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate); 33069-62-4/Paclitaxel

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