Oleic acid-based nanosystems for mitigating acute respiratory distress syndrome in mice through neutrophil suppression: how the particulate size affects therapeutic efficiency
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 anti-inflammatory 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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Posted 13 Jan, 2020
Received 17 Jan, 2020
Received 12 Jan, 2020
Invitations sent on 10 Jan, 2020
On 10 Jan, 2020
On 10 Jan, 2020
On 09 Jan, 2020
On 08 Jan, 2020
On 08 Jan, 2020
Received 13 Dec, 2019
Received 13 Dec, 2019
On 13 Dec, 2019
Received 12 Dec, 2019
Received 08 Dec, 2019
On 01 Dec, 2019
On 29 Nov, 2019
Invitations sent on 28 Nov, 2019
On 28 Nov, 2019
On 28 Nov, 2019
On 27 Nov, 2019
On 27 Nov, 2019
On 26 Nov, 2019
On 26 Nov, 2019
Oleic acid-based nanosystems for mitigating acute respiratory distress syndrome in mice through neutrophil suppression: how the particulate size affects therapeutic efficiency
Posted 13 Jan, 2020
Received 17 Jan, 2020
Received 12 Jan, 2020
Invitations sent on 10 Jan, 2020
On 10 Jan, 2020
On 10 Jan, 2020
On 09 Jan, 2020
On 08 Jan, 2020
On 08 Jan, 2020
Received 13 Dec, 2019
Received 13 Dec, 2019
On 13 Dec, 2019
Received 12 Dec, 2019
Received 08 Dec, 2019
On 01 Dec, 2019
On 29 Nov, 2019
Invitations sent on 28 Nov, 2019
On 28 Nov, 2019
On 28 Nov, 2019
On 27 Nov, 2019
On 27 Nov, 2019
On 26 Nov, 2019
On 26 Nov, 2019
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 anti-inflammatory 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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
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Figure 7