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Oleic acid-based nanosystems for mitigating acute respiratory distress syndrome in mice through neutrophil suppression: how the particulate size affects therapeutic efficiency
Jia-You Fang
Chang Gung University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-2114-7709
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.
Keywords
oleic acid; lipid-based nanoparticles; size; anti-inflammation; neutrophil; acute respiratory distress syndrome
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Received 17 Jan, 2020
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On 10 Jan, 2020
Editor assigned
On 09 Jan, 2020
Submission checks complete
On 08 Jan, 2020
Editor invited
On 08 Jan, 2020
No comments provided
Review #2 received
Received 13 Dec, 2019
Review #3 received
Received 13 Dec, 2019
Editorial decision: Major revision
On 13 Dec, 2019
Review #4 received
Received 12 Dec, 2019
Review #1 received
Received 08 Dec, 2019
Reviewer #4 agreed
On 01 Dec, 2019
Reviewer #3 agreed
On 29 Nov, 2019
Reviewers invited
Invitations sent on 28 Nov, 2019
Reviewer #1 agreed
On 28 Nov, 2019
Reviewer #2 agreed
On 28 Nov, 2019
First submitted
On 27 Nov, 2019
Editor assigned
On 27 Nov, 2019
Submission checks complete
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This preprint is under consideration at Journal of Nanobiotechnology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Oleic acid-based nanosystems for mitigating acute respiratory distress syndrome in mice through neutrophil suppression: how the particulate size affects therapeutic efficiency
Jia-You Fang
Chang Gung University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-2114-7709
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 2
Posted 13 Jan, 2020
No community comments so far
Review #2 received
Received 17 Jan, 2020
Review #1 received
Received 12 Jan, 2020
Reviewers invited
Invitations sent on 10 Jan, 2020
Reviewer #1 agreed
On 10 Jan, 2020
Reviewer #2 agreed
On 10 Jan, 2020
Editor assigned
On 09 Jan, 2020
Submission checks complete
On 08 Jan, 2020
Editor invited
On 08 Jan, 2020
No comments provided
Review #2 received
Received 13 Dec, 2019
Review #3 received
Received 13 Dec, 2019
Editorial decision: Major revision
On 13 Dec, 2019
Review #4 received
Received 12 Dec, 2019
Review #1 received
Received 08 Dec, 2019
Reviewer #4 agreed
On 01 Dec, 2019
Reviewer #3 agreed
On 29 Nov, 2019
Reviewers invited
Invitations sent on 28 Nov, 2019
Reviewer #1 agreed
On 28 Nov, 2019
Reviewer #2 agreed
On 28 Nov, 2019
First submitted
On 27 Nov, 2019
Editor assigned
On 27 Nov, 2019
Submission checks complete
On 26 Nov, 2019
Editor invited
On 26 Nov, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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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