Synergic modulation of the inflammatory state of macrophages utilizing anti-oxidant and phosphatidylserine-containing polymer–lipid hybrid nanoparticles

Abstract

Inflammatory activation of macrophages is a key factor in chronic inflammatory diseases such as ulcerative colitis. The excessive production of reactive oxygen species (ROS)/reactive nitrogen species (RNS) by macrophages causes oxidative stress during the inflammatory response and exaggerates inflammatory lesions in ulcerative colitis. Inhibition of the inflammatory activation of macrophages is a promising treatment for chronic inflammatory diseases. Here, we prepared self-filling polymer-lipid hybrid nanoparticles (PST-PLNPs) consisting of poly dl-lactic acid as a hydrophobic biodegradable polymer core encapsulating α-tocopherol (T) and phosphatidylserine (PS) both on the surface and interior of the particle. We confirmed the anti-inflammatory response of these hybrid nanoparticles in activated murine macrophages. PS has anti-inflammatory effects on macrophages by modulating the macrophage phenotype, while α-tocopherol is an antioxidant that neutralizes ROS. We found that PS-containing (PS-PLNPs) and PS plus α-tocopherol-containing (PST-PLNPs) polymer-lipid hybrid nanoparticles significantly increased the viability of lipopolysaccharide (LPS)-treated macrophages compared with phosphatidylcholine-containing PLNPs. PST-PLNPs had a better effect than PS-PLNPs, which was attributed to the synergy between PS and α-tocopherol. This synergic action of PST-PLNPs reduced NO and pro-inflammatory cytokine (IL-6) production and increased anti-inflammatory cytokine (TGF-β1) production when incubated with activated macrophages. Thus, these self-filling biodegradable polymer-lipid hybrid nanoparticles (PST-PLNPs) containing anti-oxidant and anti-inflammatory molecules might be potential alternative drug carriers to liposomes and polymeric nanoparticles for the treatment of chronic inflammatory diseases such as ulcerative colitis.

Modulating Lipid-Polymer Nanoparticles’ Physicochemical Properties to Alter Macrophage Uptake

“…PS, stiff, and large being the characteristic levels that increased uptake of LPNPs corresponds with findings from other groups throughout literature when these characteristics were tested individually. − When all three favorable characteristics were present (PS-St-L), there was the greatest uptake by a large margin. This is the only formulation that produced significantly higher uptake compared with other PS-coated LPNPs.…”

“…Nanoparticle properties can also affect macrophages’ ability to endocytose nanoparticles through different pathways. Studies modulating one property at a time (i.e., surface coating, size, or stiffness) indicate that nanoparticles with PS, − stiffer nanoparticles, − and larger nanoparticles − tend to be taken up faster and to a higher degree than those without PS, those that are softer, and those that are smaller. However, the impact of the interactions among these characteristics on macrophage uptake has not been widely studied.…”

Recent trends and scenario of antibiotic use in veterinary practices for livestock production in Bangladesh: a review

“…Antimicrobial peptides, hybrid nanoparticles containing anti-inflammatory agents etc.) elicit a passive immune response by transfer of antibodies and changing the inflammatory responses of the host (Hosain et al, 2017;Kumar et al, 2015). The immune modulators stimulate the immune system in a process that is less dependent on the pathogen causing infection, which makes them effective for a broad range of pathogens (Hye et al, 2006).…”