Preparation and biodisposition of methoxypolyethylene glycol amine-poly(DL-lactic acid) copolymer nanoparticles loaded with pyrene-ended poly(DL-lactic acid)

Int J Pharm. 2008 Jun 24;358(1-2):271-7. doi: 10.1016/j.ijpharm.2008.03.011. Epub 2008 Mar 18.

Abstract

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.

MeSH terms

  • Animals
  • Chromatography, Gel
  • Fluorescent Dyes
  • Indicators and Reagents
  • Injections, Intravenous
  • Lactic Acid / chemical synthesis
  • Lactic Acid / chemistry*
  • Lactic Acid / pharmacokinetics
  • Magnetic Resonance Spectroscopy
  • Male
  • Mice
  • Microscopy, Electron, Transmission
  • Nanoparticles / chemistry*
  • Particle Size
  • Polyesters
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry*
  • Polyethylene Glycols / pharmacokinetics
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • Polymers / pharmacokinetics
  • Pyrenes / chemical synthesis
  • Pyrenes / chemistry*
  • Pyrenes / pharmacokinetics
  • Sarcoma 180 / metabolism
  • Tissue Distribution

Substances

  • Fluorescent Dyes
  • Indicators and Reagents
  • Polyesters
  • Polymers
  • Pyrenes
  • Lactic Acid
  • Polyethylene Glycols
  • poly(lactide)
  • monomethoxypolyethylene glycol