Round 1

Reviewer 1 Report

The issues of antioxidant therapy and the theory of lipid peroxidation itself as the physiological basis of aging are modern and widely discussed. The peer-reviewed work on the state of the art in nanoantioxidant development was supported by a research grant from  King Khalid University through the Large Groups Project under grant number RGP 01.02.43 and is a review of literary sources grouped according to the studied groups of substances with the allocation of groups of metal salts with variable valence. Therefore, the present work is a review. This Review cannot be considered systematic as it does not meet all the requirements of PRISMA.

My comments are:

Significance. 

1. The information presented in the manuscript is not analyzed by the authors in terms of the validity, reliability of the results obtained and the correctness of the study, but only notes the conclusions made by other researchers in the cited works. An analysis of the results obtained by various researchers with the formulation of pros and cons would strengthen the present review.

Quality of Presentation.

 2. The sequence of presentation of the material, the tabular grouping by main chemical groups and the graphical representation of the ongoing processes contribute to the understanding of the article by the reader.

Figures. I did not check the originality of the Figures. In my opinion, some figures (especially Fig. 1-2-3) do not carry additional information, repeat the text, and therefore are superfluous.

3.  Organization and details of work needs to be improved. It is advisable to add to the structure of the manuscript:

4 In the INTRODUCTION section, add the purpose of this manuscript, provide clearly formulated objectives of the issues you are considering ..

5  There is no information in the manuscript about the methods of writing this review. It is advisable to add a section in which you describe the principles by which you conducted the literature search. What bases did you use and for what period. What were the inclusion and non-inclusion criteria. As a result, the selection of studies was carried out. Describe the process of collecting and analyzing literary sources.

6.  Add a subsection about Risk of bias across studies (or Risk of bias in individual studies) Specify any assessment of risk of bias that may affect the cumulative evidence

7. Add a DISCUSSION section in which you search for the main findings of your work, including the strength of evidence for each main outcome

8. Add subsection Limitations. Discuss limitations at study and outcome level, and at review-level. Describe the weaknesses of this work and the prospects for further work.

 Scientific Soundness.

9. According to PubMed, over the past 10 years, the number of works with the keyword antioxidants and antioxidant effect is 290093, including 3492 nanooxidants. The authors review 212 publications. Since the principle of choosing a published study is not explained or there is no independent analysis of the article cited in the review, it is not possible to fully express the reliability of the above conclusions. Although, given the youth of the discussed direction in modern pharmacology, I fully agree with the position on the need for further study of this promising direction.

 10. General final comment

The clear merit of the authors lies in the fact that, based on published studies, they proposed classifications of antioxidants using nanotechnology based on biological and chemical differences. This will help scientists working in different directions to evaluate the effectiveness of newly created substances with an antioxidant effect in the size of nanoparticles to achieve the maximum effect due to better penetration through biological membranes and an increase in targeted delivery of the actual active molecules.

The manuscript will certainly increase interest in the problem of antioxidants, but will have little effect on the significance of the types and types of coatings, the technologies for its application and the achievement of maximum stability, which, from the point of view of the reviewer, is the task of this journal. Perhaps the collected material should be restructured with an emphasis on the target audience, then the interest in the presented review will undoubtedly increase.

Given the title of the journal, more attention should be given to coatings and/or a section specifically on Coatings that stabilize the dosage form or allow targeted delivery should be added. It is also advisable to add such information to the introduction section.

Author Response

We thank the Reviewer #1, for the valuable comments on our manuscript. These comments helped us to improve the manuscript quality and presentation style.

Please refer below to responses for the reviewer comments. We hope that these replies are sufficient to answer the queries and objections raised by the reviewer 1

Author Response File: Author Response.pdf

Reviewer 2 Report

There are so many small (1-2 sentence) paragraphs in the manuscript. Suggest merging them as needed

Comments for author File: Comments.pdf

Author Response

We appreciate Reviewer No. 2's insightful comments on our paper. We enhanced the quality of the manuscript and polished the presentation thanks to the feedback we received. The reviewer's comments and our responses are highlighted in pink/yellow.

We sincerely hope that reviewer 2 would find these responses satisfactory in addressing his/her concerns.

Author Response File: Author Response.pdf

Reviewer 3 Report

11 July 2022

Journal: coatings

Title: Nanoantioxidants; The Fourth Generation of Antioxidants; Recent Research Roadmap and Future Perspectives

Comments to authors:

1-      Why the authors add Fourth Generation to the title?

2-      The graphical abstract is highly recommended.

3-      "Natural and synthetic antioxidants have similar effects"; please double-check and explain in more details

4-      "atmospheric O2" should be "atmospheric O₂"

5-      The authors could benefit from the following reference in the introduction:

Yosri, N., Khalifa, S.A., Guo, Z., Xu, B., Zou, X. and El-Seedi, H.R., 2021. Marine organisms: Pioneer natural sources of polysaccharides/proteins for green synthesis of nanoparticles and their potential applications. International Journal of Biological Macromolecules, 193, pp.1767-1798.

6-      " 19th and early 20th" should be " 19^th and early 20^th"

7-      Could you add the physiochemical properties of the nanoantioxidants?

8-      What about the metabolism of these nanoantioxidants?

9-      Figures on antioxidant mechanisms should be added

10-  The authors would add the originality of the work.

11-  The discussion part should be added to discuss the main outcome in detail

12-  The conclusion section should be reduced to focus on the main results

Taken together:

·         The authors would unify the style of the references based on the journal instructions.

·         English editing is highly required.

·         Please, re-check the punctuations, syntax, and English grammar throughout the manuscript.          

Author Response

We would like to thank the reviewer #3 for his or her feedback on our manuscript. To thank you, we have made considerable changes to the manuscript and its general appearance. You'll find our comments to the reviewer's queries and suggestions in the sections that follow. We believe that our responses to the reviewer's concerns and concerns are adequate.

Author Response File: Author Response.pdf

Reviewer 4 Report

1.       I consider that the sentences from the following lines should be reconsidered:

-          lines 96-97

-          lines 102-105

-          lines 256-258

-          lines 277-279

-          lines 284-286

-          lines 296-299

-          lines 301-303

-          lines 336-339

-          lines 386-388

-          lines 469-473

-          lines 570-572

-          lines 583-586

-          lines 620-623

2.       After section ”4. Classification of antioxidant action ” the section “ 7.1 Gold Nanoparticles (AuNPs) ” has been numbered. The order of the text must be reconsidered

3.       Some abbreviations are used without explaining the meaning or before explaining the meaning. Please correct these inconsistencies.

Author Response

We thank the Reviewer #4, for the valuable comments on our manuscript. These comments helped us to improve the manuscript quality and presentation style. Please refer below to responses for the reviewer comments. We hope that these replies are sufficient to answer the queries and objections raised by the reviewer 4.

Author Response File: Author Response.pdf

Round 2

Reviewer 3 Report

Dear Editor

Yes, it has been modified according to our suggestions.

I recommend the paper for publication.

Kindest regards, Nermeen

Reviewer 4 Report

The authors have made the requested corrections, and the article can be published in its current form