PEG liposomalization of paclitaxel improved its in vivo disposition and anti-tumor efficacy

Yuta Yoshizawa, Yusuke Kono, Ken Ichi Ogawara, Toshikiro Kimura, Kazutaka Higaki

Research output: Contribution to journalArticle

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Abstract

To find out potent paclitaxel (PTX) formulations for cancer chemotherapy, we formulated PTX in O/W emulsion and liposome selected as candidates of nanocarriers for PTX. Surface modification of these nanoparticles with polyethylene glycol (PEG) improved their in vivo behavior, but the effect of PEGylation on the pharmacokinetics of emulsion was not so remarkable and the release of PTX from emulsion was found to be very fast in blood circulation, indicating that emulsion would not be an adequate formulation for PTX. On the other hand, AUC of PEG liposome was 3.6 times higher than that of naked liposome after intravenous injection into normal rats due to the lower disposition into the reticuloendothelial system tissues such as liver and spleen. Since PEG liposome was able to stably encapsulate PTX in blood, AUC of PTX was also extensively enhanced after intravenous dosing of PTX-PEG liposome into normal rats. In the in vivo studies utilizing Colon-26 solid tumor-bearing mice, it was confirmed that PTX-PEG liposome delivered significantly larger amount of PTX to tumor tissue and provided more excellent anti-tumor effect than PTX-naked liposome. These results suggest that PEG liposome would serve as a potent PTX delivery vehicle for the future cancer chemotherapy.

Original languageEnglish
Pages (from-to)132-141
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume412
Issue number1-2
DOIs
Publication statusPublished - Jun 30 2011

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Paclitaxel
Liposomes
Neoplasms
Emulsions
Area Under Curve
Drug Therapy
Mononuclear Phagocyte System
Blood Circulation
Intravenous Injections
Nanoparticles
Colon
Spleen
Pharmacokinetics

Keywords

  • EPR effect
  • Paclitaxel
  • Passive targeting
  • PEG emulsion
  • PEG liposome

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

PEG liposomalization of paclitaxel improved its in vivo disposition and anti-tumor efficacy. / Yoshizawa, Yuta; Kono, Yusuke; Ogawara, Ken Ichi; Kimura, Toshikiro; Higaki, Kazutaka.

In: International Journal of Pharmaceutics, Vol. 412, No. 1-2, 30.06.2011, p. 132-141.

Research output: Contribution to journalArticle

Yoshizawa, Yuta ; Kono, Yusuke ; Ogawara, Ken Ichi ; Kimura, Toshikiro ; Higaki, Kazutaka. / PEG liposomalization of paclitaxel improved its in vivo disposition and anti-tumor efficacy. In: International Journal of Pharmaceutics. 2011 ; Vol. 412, No. 1-2. pp. 132-141.
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