Oleic acid-based nanosystems for mitigating acute respiratory distress syndrome in mice through neutrophil suppression: how the particulate size affects therapeutic efficiency

Abstract

Background: Oleic acid (OA) is reported to show anti-inflammatory activity toward activated neutrophils. It is also an important material in nanoparticles for increased stability and cellular internalization. We aimed to evaluate the antiinflammatory activity of injectable OA-based nanoparticles for treating lung injury. Different sizes of nanocarriers were prepared to explore the effect of nanoparticulate size on inflammation inhibition. Results: The nanoparticles were fabricated with the mean diameters of 105, 153, and 225 nm. The nanocarriers were ingested by isolated human neutrophils during a 5-min period, with the smaller sizes exhibiting greater uptake. The size reduction led to the decrease of cell viability and the intracellular calcium level. The OA-loaded nanosystems dose-dependently suppressed the superoxide anion and elastase produced by the stimulated neutrophils. The inhibition level was comparable for the nanoparticles of different sizes. In the ex vivo biodistribution study, the pulmonary accumulation of nanoparticles increased following the increase of particle size. The nanocarriers were mainly excreted by the liver and bile clearance. Mice were exposed to intratracheal lipopolysaccharide (LPS) to induce acute respiratory distress syndrome (ARDS), like lung damage. The lipid-based nanocarriers mitigated myeloperoxidase (MPO) and cytokines more effectively as compared to OA solution. The larger nanoparticles displayed greater reduction on MPO, TNF-α, and IL-6 than the smaller ones. The histology confirmed the decreased pulmonary neutrophil recruitment and lung-architecture damage after intravenous administration of larger nanoparticles. Conclusions: Nanoparticulate size, an essential property governing the anti-inflammatory effect and lung-injury therapy, had different effects on activated neutrophil inhibition and in vivo therapeutic efficacy.

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“…This uptake is energetically less favorable [ 45 ]. Lipid-based nanoparticles can be classified as soft but not rigid structures that facilitate easy internalization by cells [ 46 ]. Neutrophil influx into peripheral organs mediates sepsis through superoxide generation.…”

Pequi (Caryocar brasiliense Cambess)-Loaded Nanoemulsion, Orally Delivered, Modulates Inflammation in LPS-Induced Acute Lung Injury in Mice

“…This can be explained because this fatty acid can suppress, enhance, or synergize neutrophil function, depending on the experimental condition and the applied dose [ 39 , 40 ]. Moreover, the studies show also that the use of nanocarriers can enhance the oleic acid anti-inflammatory activity [ 41 ]. In another study, it was observed that nanostructured lipids containing oleic acid inhibit human neutrophil superoxide generation and elastase release induced by albumin in vitro, and ameliorate the neutrophil infiltration and severity of mice skin inflammation induced by leukotriene B4 in vivo [ 42 ].…”

Could natural products modulate early inflammatory responses, preventing acute respiratory distress syndrome in COVID-19-confirmed patients?

“…Decrease of pulmonary neutrophil recruitment and lung damage. [ 63 ] Acrocomia crispa fruits lipid extract LPS-induced mice lung injury In vivo Mice were pretreated with emulsified lipid extract of Acrocomia crispa fruits at 25, 50, 100 and 200 mg/kg by gavage administration. Posteriorly (1 h after the pretreatment), LPS at 20 mg/kg was intraperitoneally administered to induce lung injury in mice.…”

“…This molecule decreased pulmonary damage and neutrophil recruitment. Furthermore, this molecule also regulated inflammatory cytokines [ 63 ]. Similar results were found by Mena et al (2019) for a lipid extract of Acrocomia crispa fruits, which reduced mice lung edema and histological scores after LPS-induced mice lung injury [ 64 ].…”