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

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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 8 h, 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.

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