Influences of surface coating of PLGA nanoparticles on immune activation of macrophages

Poly(lactide-co-glycolide) (PLGA) is one of the most attractive biodegradable polymers for loading and delivering payloads, especially in the form of nanoparticles (NPs). In this work, NPs of PLGA with 3 different molecular weights were fabricated using bovine serum albumin (BSA) and polyethyleneimine (PEI) as dispersing agents. Elemental analysis revealed that the loading amounts of BSA and PEI were 40-60 μg mg^-1 and 12-15 μg mg^-1 in the BSA/PLGA NPs and PEI/PLGA NPs, respectively. About 13-18 μg mg^-1 BSA was exposed onto the surface of the BSA/PLGA NPs. No degradation of the PLGA NPs was detected after being incubated in artificial lysosomal fluid or with macrophages in a culture medium for 7 days. The innate immune activation behavior of the BSA/PLGA and PEI/PLGA NPs was evaluated by co-incubation with RAW264.7 cells in vitro. PLGA NPs fabricated with different molecular weights of PLGA showed no difference in stimulating RAW264.7 cells. The PEI/PLGA NPs did not show significant immune activation in terms of secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) too. By contrast, the BSA/PLGA NPs induced a significantly higher expression of TNF-α, likely due to the heterogeneous albumin and existence of endotoxin, and the synergistic role of larger uptake of the BSA/PLGA NPs by macrophages.

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