Effects of particle size and release property of paclitaxel-loaded nanoparticles on their peritoneal retention and therapeutic efficacy against mouse malignant ascites

Yusuke Kono, Aya Fushimi, Yuta Yoshizawa, Kazutaka Higaki, Ken-ichi Ogawara

Research output: Contribution to journalArticlepeer-review

Abstract

Malignant ascites accounts for abdominal pain, dyspnea and anorexia, all of which decrease quality of life in cancer patients. Intraperitoneal chemotherapy is a useful method for managing malignant ascites and nanoparticulate drug delivery system makes it more effective by increasing peritoneal retention of anti-cancer drugs. In this study, we prepared paclitaxel-loaded emulsions and liposomes with different particle sizes and drug release properties, and evaluated their peritoneal retention and therapeutic efficacy in Ehrlich's ascites carcinoma (EAC)-bearing mice. Liposomes with the size of 100 nm were rapidly absorbed from peritoneal cavity into blood after intraperitoneal injection into EAC-bearing mice, whereas 1000-nm liposomes were highly retained in peritoneal cavity. Accordingly, 1000 nm liposomes significantly prolonged survival time of EAC-bearing mice but did not inhibit the ascites accumulation because of too poor paclitaxel release. On the other hand, although peritoneal retention of emulsions themselves was similar irrespective of their sizes, 270-nm emulsions showed the higher PTX retention in ascites than other emulsions, and resulted in significantly prolonged survival time and lower accumulation of ascites in EAC-bearing mice. These results indicate that not only particle size but drug release property is one of key determinants of the biodisposition and therapeutic efficacy of intraperitoneally injected nanoparticulate PTX against malignant ascites.

Original languageEnglish
Article number121904
JournalInternational Journal of Pharmaceutics
Volume623
DOIs
Publication statusPublished - Jul 25 2022

Keywords

  • Emulsion
  • Intraperitoneal chemotherapy
  • Liposome
  • Malignant ascites
  • Paclitaxel

ASJC Scopus subject areas

  • Pharmaceutical Science

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