title: Accelerated blood clearance phenomenon upon repeated injection of PEG-modified PLA-nanoparticles.
abstract: OBJECTIVE
  We recently developed prostaglandin E(1) (PGE(1))-encapsulated nanoparticles, prepared with a poly(lactide) homopolymer (PLA, Mw = 17,500) and monomethoxy poly(ethyleneglycol)-PLA block copolymer (PEG-PLA) (NP-L20). In this study, we tested whether the accelerated blood clearance (ABC) phenomenon is observed with NP-L20 and other PEG-modified PLA-nanoparticles in rats.
  
  
  METHODS
  The plasma levels of PGE(1) and anti-PEG IgM antibody were determined by EIA and ELISA, respectively.
  
  
  RESULTS
  Second injections of NP-L20 were cleared much more rapidly from the circulation than first injections, showing that the ABC phenomenon was induced. This ABC phenomenon, and the accompanying induction of anti-PEG IgM antibody production, was optimal at a time interval of 7 days between the first and second injections. Compared to NP-L20, NP-L33s that were prepared with PLA (Mw = 28,100) and have a smaller particle size induced production of anti-PEG IgM antibody to a lesser extent. NP-L20 but not NP-L33s gave rise to the ABC phenomenon with a time interval of 14 days. NP-L33s showed a better sustained-release profile of PGE(1) than NP-L20.
  
  
  CONCLUSIONS
  This study revealed that the ABC phenomenon is induced by PEG-modified PLA-nanoparticles. We consider that NP-L33s may be useful clinically for the sustained-release and targeted delivery of PGE(1).
authors.affiliation: Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto, 862-0973, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ishihara
authors.forename: Miho
authors.initials: M
authors.lastname: Takeda
authors.forename: Haruka
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kimoto
authors.forename: Chisa
authors.initials: C
authors.lastname: Kobayashi
authors.forename: Naoko
authors.initials: N
authors.lastname: Takasaki
authors.forename: Kanae
authors.initials: K
authors.lastname: Yuki
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Takenaga
authors.forename: Rie
authors.initials: R
authors.lastname: Igarashi
authors.forename: Taishi
authors.initials: T
authors.lastname: Maeda
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamakawa
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Masami
authors.initials: M
authors.lastname: Otsuka
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Ishida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiwada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Mizushima
authors.forename: Tohru
authors.initials: T
authors.lastname: Mizushima
mesh_terms: D000818:Animals; D001776:Blood Circulation Time / Q000187:drug effects; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D053758:Nanoparticles / Q000008:administration & dosage*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols