Evasion of the accelerated blood clearance phenomenon by coating of nanoparticles with various hydrophilic polymers

Tsutomu Ishihara, Taishi Maeda, Haruka Sakamoto, Naoko Takasaki, Masao Shigyo, Tatsuhiro Ishida, Hiroshi Kiwada, Yutaka Mizushima, Tohru Mizushima

Research output: Contribution to journalArticlepeer-review

127 Citations (Scopus)


The accelerated blood clearance (ABC) phenomenon is induced upon repeated injections of poly(ethylene glycol) (PEG)-coated colloidal carriers. It is essential to suppress this phenomenon in a clinical setting because the pharmacokinetics must be reproducible. In this study, we evaluated the induction of the ABC phenomenon using nanoparticles coated with various hydrophilic polymers instead of PEG. Nanoparticles encapsulating prostaglandin E1 were prepared by the solvent diffusion method from a blend of poly(lactic acid) (PLA) and block copolymers consisting of various hydrophilic polymers and PLA. Coating of nanoparticles with poly(N-vinyl-2-pyrrolidone) (PVP), poly(4-acryloylmorpholine), or poly(N,N-dimethylacrylamide) led to extended residence of the nanoparticles in blood circulation in rats, although they had a shorter half-life than the PEG-coated nanoparticles. The ABC phenomenon was not induced upon repeated injection of PVP-coated nanoparticles at various time intervals, dosages, or frequencies, whereas it was elicited by PEG-coated nanoparticles. In addition, anti-PVP IgM antibody, which is estimated to be one of the crucial factors for induction of the ABC phenomenon, was not produced after injection of PVP-coated nanoparticles. These results suggest that the use of PVP, instead of PEG, as a coating material for colloidal carriers can evade the ABC phenomenon.

Original languageEnglish
Pages (from-to)2700-2706
Number of pages7
Issue number10
Publication statusPublished - 2010 Oct 11
Externally publishedYes

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry


Dive into the research topics of 'Evasion of the accelerated blood clearance phenomenon by coating of nanoparticles with various hydrophilic polymers'. Together they form a unique fingerprint.

Cite this