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.