Targeting chemotherapy of brain tumor using liposome-encapsulated cisplatin—Part 1. Substances associated with liposomes to target brain tumor

Shobu Shibata, Takafumi Jinnouchi, Akira Ochi, Kazuo Mori, Toshinori Sato, Junzo Sunamoto

Research output: Contribution to journalArticle

Abstract

The chemotherapeutic anticancer agent cisplatin (cis-diammninedichloroplatinum, CDDP) has several disadvantages, such as its extreme nephrotoxity and rapid binding to plasma proteins, and also poor penetration in the central nervous system. Liposomes therefore seemed to be suitable carriers to overcome these problems. Liposomes were investigated as a carrier for the delivery of therapeutic agents to target brain tumors. Four kinds of liposomes were prepared : neutrial liposome (phosphatidylcholine and cholesterol), positively charged liposome (added stearyl amine), negatively charged liposome (added phosphatidic acid) and neutral liposome with low membrane fluidity (dipalmitoylphosphatidylcholine and cholesterol). As for the uptake of radioactivity in the brain tumor, spleen, liver, kidney and brain 30 minutes after the injection of liposomes labeled with 14C into the 9L cells implanted brain tumor rats, the spleen had the highest uptake of radioactivity. The uptake was also greater in the brain tumor and lower in the kidney as compared to using cisplatin alone. The brain tumor uptake were in order of neutral liposome with low membrane fluidity, neutral liposome, negatively charged liposme and positively charged liposome. The cytotoxity of cisplatin against 9L-glioma cells was not decrease by encapsulation of liposomes. These results indicate that liposomes-encapsulated cisplatin could be utilized for targeting the chemotherapy of brain tumors, however in order to increase the targetability of liposome to brain tumors, we have developed the coating of liposomes with a cell specific polysaccharide.

Original languageEnglish
Pages (from-to)83-87
Number of pages5
JournalDrug Delivery System
Volume5
Issue number2
DOIs
Publication statusPublished - 1990
Externally publishedYes

Keywords

  • 9L rat brain tumor
  • cisplatin
  • drug delivery
  • liposome

ASJC Scopus subject areas

  • Pharmaceutical Science

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