Evaluation of long-circulating nanoparticles using biodegradable ABA triblock copolymers containing of poly(L-lactic acid) A-blocks attached to central poly(oxyethylene) B-blocks in vivo

The nanoparticles (mean diameter 152-377 nm) ,consisting of the ABA triblock copolymers (M-w 29000-147000) containing poly(L-lactic acid) (PLA) A-blocks attached to central poly(oxyethylene) (PEG) B-blocks (PEG M-w 6600, 20000) (PLA-PEG-PLA) were prepared, and the effects of the polymer characteristics on the pharmacokinetics of the nanoparticles and the biodistribution of the nanoparticles were studied. Progesterone was used as a model drug. We could make the long-circulating nanoparticles using the triblock copolymer. The degree of burst in early phase, which was estimated by the Co values (Progesterone concentration at time 0) and the circulating-time were affected by the total M-w, the PEG content, the PEG M-w and the M-w/M-n (M-n: where M-n is the number average molecular weight) ratio. The purification of the polymer was an important factor for the control of the burst. These triblock copolymer nanoparticles induced reduction in the liver and spleen uptake of the nonoparticles. These phenomena are probably explained by the avoidence of adsorption of opsonin to the particles as a result of the orientation of PEG on the surface of the particles. (C) 1998 Elsevier Science B.V. All rights reserved.