Albumin-conjugated PEG liposome enhances tumor distribution of liposomal doxorubicin in rats

Jun ichi Yokoe, Shiho Sakuragi, Kayoko Yamamoto, Takuya Teragaki, Ken-ichi Ogawara, Kazutaka Higaki, Naohisa Katayama, Toshiya Kai, Makoto Sato, Toshikiro Kimura

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)

Abstract

To evaluate the effect of coupling of recombinant human serum albumin (rHSA) onto the surface of poly(ethylene glycol)-modified liposome (PEG liposome) on the in vivo disposition characteristics of liposomal doxorubicin (DXR), the pharmacokinetics and tissue distribution of DXR were evaluated after intravenous administration of rHSA-modified PEG (rHSA/PEG) liposomal DXR into tumor-bearing rats. rHSA/PEG liposome prepared using a hetero-bifunctional cross-linker, N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP), efficiently encapsulated DXR (over 95%). rHSA/PEG liposomal DXR showed longer blood-circulating property than PEG liposomal DXR and the hepatic and splenic clearances of rHSA/PEG liposomal DXR were significantly smaller than those of PEG liposomal DXR. It was also demonstrated that the disposition of DXR to the heart, one of the organs for DXR-related side-effects, was significantly smaller than free DXR. Furthermore, the tumor accumulation of rHSA/PEG liposomal DXR was significantly larger than that of PEG liposomal DXR. The "therapeutic index", a criterion for therapeutic outcome, for rHSA/PEG liposomal DXR was significantly higher than PEG liposomal DXR. These results clearly indicate that rHSA-conjugation onto the surface of PEG liposome would be a useful approach to increase the effectiveness and safety of PEG liposomal DXR.

Original languageEnglish
Pages (from-to)28-34
Number of pages7
JournalInternational Journal of Pharmaceutics
Volume353
Issue number1-2
DOIs
Publication statusPublished - Apr 2 2008

Keywords

  • Doxorubicin
  • PEG liposome
  • Passive targeting
  • Recombinant human serum albumin (rHSA)
  • Tumor-bearing rats

ASJC Scopus subject areas

  • Pharmaceutical Science

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