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

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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

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Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Yokoe, J. I., Sakuragi, S., Yamamoto, K., Teragaki, T., Ogawara, K. I., Higaki, K., Katayama, N., Kai, T., Sato, M., & Kimura, T. (2008). Albumin-conjugated PEG liposome enhances tumor distribution of liposomal doxorubicin in rats. International Journal of Pharmaceutics, 353(1-2), 28-34. https://doi.org/10.1016/j.ijpharm.2007.11.008