Preparation and biodisposition of methoxypolyethylene glycol amine-poly(DL-lactic acid) copolymer nanoparticles loaded with pyrene-ended poly(DL-lactic acid).
A formyl group-ended poly(DL-lactic acid) (PLA-aldehyde), synthesized in the same manner as reported previously, was utilized to produce the polymeric marker for PLA-related nanoparticles. Namely, pyrene-ended poly(DL-lactic acid) (PLA-pyrene) was prepared as a polymeric marker by the reductive amination of PLA-aldehyde and aminopyrene. Methoxypolyethylene glycol amine-poly(DL-lactic acid) block copolymer (PLA-(MeO-PEG) nanoparticles loaded with PLA-pyrene were prepared, and examined on retention of PLA-pyrene in the nanoparticles, and biodisposition in normal and sarcoma-180 solid tumor-bearing mice. PLA-pyrene was retained stably in PLA-(MeO-PEG) nanoparticles in a PBS-ethanol (7:3, v/v) mixture and a plasma-PBS (1:1, v/v) mixture, indicating that PLA-pyrene might be a useful marker of PLA-(MeO-PEG) nanoparticles themselves. After i.v. injection in normal rats, the plasma level of PLA-pyrene was very high for initial 8h, and accumulated gradually into organs, especially spleen and liver. After i.v. injection in tumor-bearing mice, similar biodistribution profiles of PLA-pyrene were observed, and PLA-pyrene was accumulated well in tumor, suggesting that PLA-(MeO-PEG) nanoparticles should be delivered efficiently to solid tumors. It is suggested that PLA-pyrene might be a useful probe of the nanoparticles themselves. In addition, it was demonstrated that PLA-(MeO-PEG) nanoparticles should be a useful drug carrier for passive tumor targeting.
Sasatsu
Masanaho
M
Department of Drug Delivery Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, Japan.
Onishi
Hiraku
H
Machida
Yoshiharu
Y
D000818:Animals; D002850:Chromatography, Gel; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011721:Pyrenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D012510:Sarcoma 180 / Q000378:metabolism; D014018:Tissue Distribution
D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D011091:Polyesters; D011108:Polymers; D011721:Pyrenes; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); C028210:monomethoxypolyethylene glycol