Particle size-dependent triggering of accelerated blood clearance phenomenon

Hiroyuki Koide, Tomohiro Asai, Kentaro Hatanaka, Takeo Urakami, Takayuki Ishii, Eriya Kenjo, Masamichi Nishihara, Masayuki Yokoyama, Tatsuhiro Ishida, Hiroshi Kiwada, Naoto Oku

Research output: Contribution to journalArticlepeer-review

105 Citations (Scopus)

Abstract

A repeat-injection of polyethylene glycol-modified liposomes (PEGylated liposomes) causes a rapid clearance of them from the blood circulation in certain cases that is referred to as the accelerated blood clearance (ABC) phenomenon. In the present study, we examined whether polymeric micelles trigger ABC phenomenon or not. As a preconditioning treatment, polymeric micelles (9.7, 31.5, or 50.2 nm in diameter) or PEGylated liposomes (119, 261 or 795 nm) were preadministered into BALB/c mice. Three days after the preadministration [3H]-labeled PEGylated liposomes (127 nm) as a test dose were administered into the mice to determine the biodistribution of PEGylated liposomes. At 24 h after the test dose was given, accelerated clearance of PEGylated liposomes from the bloodstream and significant accumulation in the liver was observed in the mice preadministered with 50.2-795 nm nanoassemblies (PEGylated liposomes or polymeric micelles). In contrast, such phenomenon was not observed with 9.7-31.5 nm polymeric micelles. The enhanced blood clearance and hepatic uptake of the test dose (ABC phenomenon) were related to the size of triggering nanoassemblies. Our study provides important information for developing both drug and gene delivery systems by means of nanocarriers.

Original languageEnglish
Pages (from-to)197-200
Number of pages4
JournalInternational Journal of Pharmaceutics
Volume362
Issue number1-2
DOIs
Publication statusPublished - Oct 1 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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