In vitro and in vivo characterization of nanoparticles made of MeO-PEG amine/PLA block copolymer and PLA

International Journal of Pharmaceutics
Masanaho SasatsuYoshiharu Machida

Abstract

The preparative method of a block copolymer of poly(dl-lactic acid) (PLA) and methoxypolyethylene glycol amine (MeO-PEG(N)), named PLA-(MeO-PEG), was refined. The degree of introduction of MeO-PEG(N) into PLA increased up to 55% (mol/mol) using a dichloromethane/methanol mixture (1:1, v/v) as a solvent at the reductive amination and taking all the fractions of the first peak in gel-chromatography. Plain and 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine (DiD)-loaded nanoparticles prepared using the PLA/PLA-(MeO-PEG) mixture of 45:55 (mol/mol) showed a mean size of 113 and 154 nm, respectively, and a positive zeta potential in water. DiD solution, i.v. administered, showed a lower plasma level and high distribution in liver, though DiD was distributed into the blood cells to a fair extent. Nanoparticles exhibited a higher plasma concentration of DiD than the DiD solution at 1 and 8h, though DiD was distributed into the liver and spleen to a fair extent. Nanoparticles made of the PLA/PLA-(MeO-PEG) mixture of 44:55 (mol/mol) showed better plasma retention than those made of the PLA/PLA-(MeO-PEG) mixture of 64:36 (mol/mol). It is suggested that the PLA/PLA-(MeO-PEG) mixture nanoparticles with a higher PEG/PLA ratio should...Continue Reading

Citations

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