Prevention of Protein Adsorption and Macrophage Phagocytosis of Perfluorocarbon-Based Microsized Core-Shell Artificial Oxygen Carriers by Facile PEG Coatings.

Polyethylene glycol (PEG)-coated microsized artificial oxygen carriers (AOCs) with a perfluorooctyl bromide (PFOB) core and poly(lactide--caprolactone) (PLC) shell were successfully fabricated using Shirasu porous glass (SPG) membrane emulsification. The PEG coating was achieved by adding the polylactide--polyethylene glycol--polylactide (PLA-PEG-PLA) block copolymer to the disperse phase during the SPG membrane emulsification process. During the DCM evaporation process, the three-layer structure of the PEG layer, PLC shell, and PFOB core of the AOCs spontaneously formed by phase separation. By adjustment of the ratio of PLA to PLA-PEG-PLA, the PEG chain density on the AOC surface was controlled and estimated as 0.1-2.4 chains nm based on quantitative proton nuclear magnetic resonance analysis. It was expected that a loop PEG brush structure was formed on the surface of the AOCs owing to the ABA block copolymer structure of PLA-PEG-PLA. With the increase in PEG chain density, nonspecific adsorption of bovine serum albumin, γ-globulin, and fibrinogen to AOCs decreased drastically and reached below 10 μg cm. Additionally, phagocytosis of the AOCs, evaluated using the macrophage cell line RAW 264.7, was effectively prevented and the phagocytosis index decreased from 2 to almost 0. Finally, the PEG-coated core-shell AOCs exhibited excellent higher cell viability to RAW 264.7 than bare AOCs and showed oxygen delivery to hypoxia-responsive HeLa cells. Effective facile PEG coating on PFOB/PLC core-shell AOCs was successfully achieved simultaneously with membrane emulsification and subsequent evaporation-induced phase separation. It will be an effective strategy for membrane emulsification technology as well as the preparation of AOCs.