PONE-D-23-15716

Route of Pulmonary Administration of Aerosols Significantly Affects Particle Deposition and Cellular RecruitmentPLOS ONE

Dear Dr. Lo,

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Abdelwahab Omri, Pharm B, Ph.D, Laurentian University

Academic Editor

PLOS ONE

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Reviewers' comments:

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Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

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Reviewer #1: Yes

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: N/A

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This paper compares the distribution of flourescent microspheres administered to mice either in an exposure chamber or by intranasal instillation. The authors show that intranasal administration results in concentration of particles around the airways, whereas the chamber produces uniform distributrion of particles throughout the lung parenchyma. A very similar result was obtained using neutrophil reporter mice in an LPS model of either chamber exposure or intranasal administration.

This is a carefully done study and the authors have taken considerable care in their methods to ensure that their results are real. I don’t have any major criticisms, but do have two minor comments:

1. The Kogel study in which mice were exposed to cigarette smoke by whole body or nose only inhalation is cited as an example of the way in which administration by different routes leads to different results. Although this is true, what it really reflects in the Kogel study is pure nasal inhalation (ie, a good mimic of human smokers) vs licking of fir and ingestion (or direct skin uptake) of a toxin (ie, a poor model of human smokers). To me this is not a good model to cite for the authors’ hypothesis.

2. While the authors are quite correct that exposure chambers produce a much more realistic model than intranasal administration, there may be instances in which intranasal adminstration produces what you want: if what you are interested in is airway toxicity, then these data suggest that intranasal adminstration may be the route to go. It might be worth making this point in the discussion.

Reviewer #2: 1. The heading only depicting the pulmonary route whereas, intranasal route is also exposed in this study. The title need to modify as there is low connection between the title and manuscript content.

2. Author misunderstood the route of delivery vs delivery system. Aerosol is a delivery mechanism. Whereas, intranasal and pulmonary are the route of drug delivery. Rewrite the sentence no 28.

3. Are these ready made microspheres? or synthesized in lab? Mention the method of preparation of dye loaded microsphere.

4.Mention the Animal Ethical permission number. Is this approved protocol? What was the environmental conditions of the animals, body weight, grouping and sex?

5.I can see the schematic diagram of the chamber in the earlier publication of the authors. It will be good to insert the real image of chamber in the manuscript.

6.What is the delivery efficiency of the chamber? During exposure, how can author signifies that the particles will be delivered through pulmonary route? The delivery pattern is hard to understand.

7. Use standard unit in this manuscript

8.What is the Zeta potential of these microspheres? included it to understand the coagulation at airway. (line no 291)

9. It will be good if author summarize the result through a table form for better understanding of comparison. While reading, I found insistence in correlating one section with other.

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Reviewer #1: No

Reviewer #2: Yes: Dr. Sujit Kumar Debnath

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Route of Administration Significantly Affects Particle Deposition and Cellular Recruitment

PONE-D-23-15716R1

Dear Dr. Lo,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Abdelwahab Omri, Pharm B, Ph.D, Laurentian University

Academic Editor

PLOS ONE