Comparison of the PLA-mPEG and mPEG-PLA-mPEG copolymersnanoparticles on the plasma proteinadsorption and in vivo biodistribution

Abstract

In order to address the chemical constitution-effect associated with the PEGylated amphiphilic block copolymer, the adsorption of the plasma proteins, in vitromacrophage uptake and in vivo biodistribution of the poly(ethylene glycol)-poly(D,L-lactic acid) (mPEG-PLA, BA) nanoparticles (NPs) and the poly(ethylene glycol)-poly(D,L-lactic acid)-poly(ethylene glycol) (mPEG-PLA-mPEG, BAB) NPs, with the same molar ratio of PEG to PLA segment of 30% and the same EG chain length of 5 kDa were investigated and compared in the present study. PLA without PEGylation was also studied as control. All the NPs formulated with the diameter of about 180 nm were prepared by a modified w/o/w technique. The BAB NPs exhibited excellent hydrophilicity and an approximately neutralized surface charge of −2.23 mV, whereas the BA NPs presented the negative charge of −13.8 mV. X-Ray photoelectron spectroscopy (XPS) revealed that the 63.73% coverage of PEG chains was achieved on the BAB NPs surface, whereas the PEG amount on the surface of BA NPs was only 21.11%. BAB polymer could suppress the adsorption of both the big protein fibrinogen (inhibition ratio of 85%) and small protein albumin (inhibition ratio of 71%) significantly. But the mPEG-PLA could only repel the adsorption of big protein with inhibition ratio of 65%. In vitro and in vivo studies indicated that compared with the BA NPs, the BAB NPs strongly prohibited the macrophage uptake and extended the circulation half-life (t_1/2) with concomitant reduced liver sequestration. Calculated t_1/2 of the BAB NPs and the BA NPs was 600 ± 50 min and 160 ± 15 min, respectively. These results indicated that compared with the BA NPs, even with the same molar ratio of PEG to PLA segment and the same EG chain length, BAB NPs could effectively inhibit the adsorption of protein and prolong the systemic circulation of NPs.