Smart Tissue Carriers for Innovative Cosmeceuticals and Nutraceuticals

Round 1

Reviewer 1 Report

Strengths

The review is a promising viewpoint on the use of environmentally friendly, sustainable, biodegradable and naturally derived carriers to replace emulsifiers standardly used in cosmetic creams, lotions, and gels. 

Weaknesses

In order to claim these natural-derived polymers and tissue-carriers sufficiently facilitate the penetration and efficacy of cosmetics, quantitative evidence of commonly measured, industry-accepted outcomes must be shown.  Instead of this evidence, the review shifts its focus to medical applications instead.  However, medical applications and devices are not cosmetics.  Medical devices must reach a higher standard of safety and efficacy.  Therefore, if the review is centered on the use of natural replacements for medical devices, it does not show any clinical evidence for their replacement.  If the review is centered on the use of natural replacements for cosmetics, then the review lacks any primary evidence that these carriers such as chitin can quantitatively improve frequently assessed cosmetic parameters.  These quantitative parameters and the instrumentation used to assess them are:  elasticity (cutometer), hydration (corneometer), oil (sebumeter), wrinkles and lines (topography, Visioscanning).  Evidence of the natural permeation enhancers, gels, etc. improving cosmetic outcomes must be shown using the above cosmetic parameters and instrumentation to claim these are legitimate replacements for existing agents such as emulsifiers, many of which are also naturally derived. 

There are numerous errors in grammar, formatting and syntax.  The English is very bad; the article is almost impossible to read and understand.

Line 13            Spacing between words Abstract, attention to singular and plural- supplements

Line 14            rich in water

Line 17            often cause allergic sensitization.

Line 24            Do not see how the content of toxic particles makes particles become normal food.  Rephrase.

Line 38            Water free, emulsifier free – evidence of skin penetration and permeation?

Line 47            Cosmetic carriers are topical vehicles used to deliver active ingredients . . .

Line 77            pathways

Line 92-95       Does not make sense.

Line 98-99       also is repeated

Line 125          Need legends and text to explain Figures

Line 152          Oral mucosa are not the route of delivery for dietary supplements.

Line 200-213   Formatting and spacing

Line 200        Evidence that polysaccharides work as emulsifiers to bring hydrohilics through the SC?

Line 236          Explain the Figure 7 information

Line 245          Explain more about how polymeric materials which are acellular can proliferate and differentiate?

Line 267          There is no data presented to support the idea that large polymers can act as carriers to carry natural ingredients released in skin layers.  Must be lipophilic and small (rule of 5) to penetrate skin.  Line 293 states they are water insoluble.

Line 280          Need to show results of nanoparticles effectively permeating intact skin to deliver common cosmetic elements such as hyaluronate, medium chain triglycerides and vitamins.

Line 300-303   These go off-topic describing medical devices.  Medical devices are not cosmetic s and are not referenced as being felt by consumers to need natural origins.

Line 320          Drifts to medical applications instead of central cosmetic topic.  No research seems to support the cosmetic use of these large, insoluble polymers for cosmetic purposes.  Line 459-same comment.

Line 321          probably spelling; oxygen spelling; Line 333

Line 350          Encapsulated polyphenols or vitamin C and E shown to reverse skin fine lines as claimed?  Should direct reference.

Author Response

The review is a promising viewpoint on the use of environmentally friendly, sustainable, biodegradable and naturally derived carriers to replace emulsifiers standardly used in cosmetic creams, lotions, and gels. 

Weaknesses

In order to claim these natural-derived polymers and tissue-carriers sufficiently facilitate the penetration and efficacy of cosmetics, quantitative evidence of commonly measured, industry-accepted outcomes must be shown.  Instead of this evidence, the review shifts its focus to medical applications instead.  However, medical applications and devices are not cosmetics.  Medical devices must reach a higher standard of safety and efficacy.  Therefore, if the review is centered on the use of natural replacements for medical devices, it does not show any clinical evidence for their replacement.  If the review is centered on the use of natural replacements for cosmetics, then the review lacks any primary evidence that these carriers such as chitin can quantitatively improve frequently assessed cosmetic parameters.  These quantitative parameters and the instrumentation used to assess them are:  elasticity (cutometer), hydration (corneometer), oil (sebumeter), wrinkles and lines (topography, Visioscanning).  Evidence of the natural permeation enhancers, gels, etc. improving cosmetic outcomes must be shown using the above cosmetic parameters and instrumentation to claim these are legitimate replacements for existing agents such as emulsifiers, many of which are also naturally derived. 

In the revised paper we have improved the information regarding works of our research group or other groups to show the effectiveness and biocompatibility of these tissues.

Comments on the Quality of English Language

There are numerous errors in grammar, formatting and syntax.  The English is very bad; the article is almost impossible to read and understand.

The paper was profoundly revised to improve the language, rephrasing many sentences.

Line 13            Spacing between words Abstract, attention to singular and plural- supplements

Thanks, spaces were revised as well as plural and singular

Line 14            rich in water

revised

Line 17            often cause allergic sensitization.

Revised and deleted in new version

Line 24            Do not see how the content of toxic particles makes particles become normal food.  Rephrase.

The molecules come from agro-food sector and plant products (including their byproducts). It was not clear. The sentences were modified accordingly. Thanks.

Line 38            Water free, emulsifier free – evidence of skin penetration and permeation?

 In the section “Composition of the proposed new tissues” more information is inserted about the effectiveness of the proposed approach as emerged from previous works, partly performed in our research group.

Line 47            Cosmetic carriers are topical vehicles used to deliver active ingredients . . .
revised

Line 77            pathways

Revised

Line 92-95       Does not make sense.

The sentence was removed.

Line 98-99       also is repeated

Revised

Line 125          Need legends and text to explain Figures

A legend was added in the caption.

Line 152          Oral mucosa are not the route of delivery for dietary supplements.

The review is general and would like to include also oral mucosa (not only ingestion), considering for instance sublingual administration of supplementary diets.

Line 200-213   Formatting and spacing

Format and spaces were revised.

Line 200        Evidence that polysaccharides work as emulsifiers to bring hydrophilics through the SC?

Chitin nanofibrils, having a positive charge on their surface, can work well as carriers.

Line 236          Explain the Figure 7 information

A few lines were inserted to explain Figure 7.

Line 245          Explain more about how polymeric materials which are acellular can proliferate and differentiate?

In line 245 the ECM structure is discussed. The tissue would like to mimick it, so that it can result higly biocompatible. The biocompatibility of the tissues was demonstrated, as reported for example in reference 45 and 46. The sentence was changed because it was not enough clear. We apologize.

Line 267          There is no data presented to support the idea that large polymers can act as carriers to carry natural ingredients released in skin layers.  Must be lipophilic and small (rule of 5) to penetrate skin.  Line 293 states they are water insoluble.

In vivo and in vitro studies reported in reference 42-46 are on the whole in agreement with an afficinet carrier activity.

Line 280          Need to show results of nanoparticles effectively permeating intact skin to deliver common cosmetic elements such as hyaluronate, medium chain triglycerides and vitamins.

In vivo tests are proposed in reference 45.

Line 300-303   These go off-topic describing medical devices.  Medical devices are not cosmetic s and are not referenced as being felt by consumers to need natural origins.

Some co-authors have worked in this field. Some affinities between these sectors are present. However, to improve the paper its revision was done to address it more to cosmeceutical and nutraceutical applications, as mentioned in the title. Thanks.

Line 320          Drifts to medical applications instead of central cosmetic topic.  No research seems to support the cosmetic use of these large, insoluble polymers for cosmetic purposes.  Line 459-same comment.

To improve the paper its revision was done to address it more to cosmeceutical and nutraceutical applications, as mentioned in the title.

Line 321          probably spelling; oxygen spelling; Line 333

Thanks, these refuses were revised.

Line 350          Encapsulated polyphenols or vitamin C and E shown to reverse skin fine lines as claimed?  Should direct reference.

References 54-56, where these studies are explained, are cited. Thanks.

Reviewer 2 Report

The review is very confusing and a clear topic does not emerge.

Introduction looks like a commentary.

The paragraph 2. “Biobased polymers and skin function” should be implemented proving more scientific information.

The same for the paragraph 3. “Smart biodegradable tissues”. Moreover, it is not clear which are these so-called “smart biodegradable tissues” and the logical and scientific relationship between the subparagraphs “3.1 Composition of the proposed new tissues”, “3.2 The activity of ROS and RNS on the aging process”, 3.3 The meaning of the expression Beauty from within” and 3.2 The necessity of the claim regarding cosmetics.

All paragraphs and subparagraphs of the review appear as unconnected parts.

Conclusions do not reflect the content of the review and they seem as another commentary.

Figures are not well formatted and for Figure 8, 9 10 and 11 the source of the figure is missing.

The title is not pertinent with the content of the review. Which are the unusual-novel carriers? They are not defined in the review and actually the review does not report and comment any carrier.

Extensive editing of English language required

Author Response

The review is very confusing and a clear topic does not emerge.

The review was conceived by the main author to explain the possibility of realizing novel nanostructured tissues containing functional molecules to be commercialized as solid product (without using emulsifiers and preservatives) for cosmeceutical and nutraceutical applications. This topic was selected because of the scientific interest and decennial experience of the co-authors in this field. We think that the confusion derives from the many aspects cared along many years in this research. So we have revised the explaination and citations to make the paper more understandable. We thank you very much for your precious suggestions.

Introduction looks like a commentary.

The introductory section title is changed in “Skin and mucous barriers”

The paragraph 2. “Biobased polymers and skin function” should be implemented proving more scientific information.

Figure 5 was changed to make it clearer and some more comments  were added to the text regarding biopolymers solubility. Thanks

The same for the paragraph 3. “Smart biodegradable tissues”. Moreover, it is not clear which are these so-called “smart biodegradable tissues” and the logical and scientific relationship between the subparagraphs “3.1 Composition of the proposed new tissues”, “3.2 The activity of ROS and RNS on the aging process”, 3.3 The meaning of the expression Beauty from within” and 3.2 The necessity of the claim regarding cosmetics.

Some titles were modified and introductory sentences were inserted where necessary to make the sections flow more understandable. In section 3 the strategy of the novel nanostructured tissue is explained, discussing also important elements to consider, including aging mechanism and social contest.

All paragraphs and subparagraphs of the review appear as unconnected parts. Conclusions do not reflect the content of the review and they seem as another commentary.

Some modification in titles was done to improve the connection between paragraphs. A new section regarding market was considered, shortening conclusions.

Figures are not well formatted and for Figure 8, 9 10 and 11 the source of the figure is missing.

Figures 8-11 were reformatted.

The title is not pertinent with the content of the review. Which are the unusual-novel carriers? They are not defined in the review and actually the review does not report and comment any carrier.

In the section “Composition of the proposed new tissues” more information is inserted about the effectiveness of the proposed approach as emerged from previous works, partly performed in our research group.

Comments on the Quality of English Language

Extensive editing of English language required

The paper was profoundly revised to improve the language, rephrasing many sentences.

Round 2

Reviewer 1 Report

The authors have clarified and included external references to support measurements of accepted cosmetic efficacies.

The English has improved but is still not easily readable.  Should be edited by outside English editor in U.S. or UK.

Author Response

The English has improved but is still not easily readable.  Should be edited by outside English editor in U.S. or UK.

Thank you for your suggestion. The paper was fully revised and rephrased by a fluent speaking co-author. U.K. english was selected. Moreover all the authors have also revised the full text. We think that the document was improved in terms of its clarity.

Reviewer 2 Report

1) Previous comment: The review is very confusing and a clear topic does not emerge. Introduction looks like a commentary.

Previous answer: The review was conceived by the main author to explain the possibility of realizing novel nanostructured tissues containing functional molecules to be commercialized as solid product (without using emulsifiers and preservatives) for cosmeceutical and nutraceutical applications. This topic was selected because of the scientific interest and decennial experience of the co-authors in this field. We think that the confusion derives from the many aspects cared along many years in this research. So we have revised the explanation and citations to make the paper more understandable. We thank you very much for your precious suggestions.

The introductory section title is changed in “Skin and mucous barriers”

Reviewer comment: I understand the point of view of the authors. However, I think that a general introduction to introduce the subject and what the authors explained in the previous answer is required for the manuscript.

2) Previous comment: The title is not pertinent with the content of the review. Which are the unusual-novel carriers? They are not defined in the review and actually the review does not report and comment any carrier.

Previous answer: In the section “Composition of the proposed new tissues” more information is inserted about the effectiveness of the proposed approach as emerged from previous works, partly performed in our research group.

Reviewer comment: The title still does not reflect the content of the review. I propose to modify it into “Smart carrier-tissues for Innovative Cosmeceuticals & Nutraceuticals” or  “ Smart nanostructured tissues for Innovative Cosmeceuticals & Nutraceuticals”.

3) Previous comment: All paragraphs and subparagraphs of the review appear as unconnected parts. Conclusions do not reflect the content of the review and they seem as another commentary.

Previous answer: Some modification in titles was done to improve the connection between paragraphs. A new section regarding market was considered, shortening conclusions

Reviewer comment: The connections among paragraph has been a little improved. However, the conclusions still do not reflect the content of the manuscript. I suggest strongly revising or re-written the conclusions to address the content of the review.

Author Response

1) Previous comment: The review is very confusing and a clear topic does not emerge. Introduction looks like a commentary.

Previous answer: The review was conceived by the main author to explain the possibility of realizing novel nanostructured tissues containing functional molecules to be commercialized as solid product (without using emulsifiers and preservatives) for cosmeceutical and nutraceutical applications. This topic was selected because of the scientific interest and decennial experience of the co-authors in this field. We think that the confusion derives from the many aspects cared along many years in this research. So we have revised the explanation and citations to make the paper more understandable. We thank you very much for your precious suggestions.

The introductory section title is changed in “Skin and mucous barriers”

Reviewer comment: I understand the point of view of the authors. However, I think that a general introduction to introduce the subject and what the authors explained in the previous answer is required for the manuscript.

 A general introduction is added in the revised manuscript to present the general subject of the work. Thanks for the suggestion.

2) Previous comment: The title is not pertinent with the content of the review. Which are the unusual-novel carriers? They are not defined in the review and actually the review does not report and comment any carrier.

Previous answer: In the section “Composition of the proposed new tissues” more information is inserted about the effectiveness of the proposed approach as emerged from previous works, partly performed in our research group.

Reviewer comment: The title still does not reflect the content of the review. I propose to modify it into “Smart carrier-tissues for Innovative Cosmeceuticals & Nutraceuticals” or  “ Smart nanostructured tissues for Innovative Cosmeceuticals & Nutraceuticals”.

Thank you for the suggestions. The first suggested title was used for the current revised version of the paper.

3) Previous comment: All paragraphs and subparagraphs of the review appear as unconnected parts. Conclusions do not reflect the content of the review and they seem as another commentary.

Previous answer: Some modification in titles was done to improve the connection between paragraphs. A new section regarding market was considered, shortening conclusions

Reviewer comment: The connections among paragraph has been a little improved. However, the conclusions still do not reflect the content of the manuscript. I suggest strongly revising or re-written the conclusions to address the content of the review.

The conclusions were almost re-written making them connected to the manuscript sections. Thank you for this suggestion allowing our paper to be ameliorated.

Round 3

Reviewer 2 Report

The manuscript is much improved from the first submission.

It is now clear the relationship between “beauty from within” and the development of green materials for cosmetics and nutraceutical products.

However, it is not still clear which is the relationship between carrier tissues and nutraceuticals. For instance, the first sentence in the abstract “The present review was conceived to explain the possibility of realizing novel nanostructured tissues containing functional molecules to be commercialized as solid product (without using emulsifiers and preservatives) for cosmeceutical and nutraceutical applications”. From this sentence, it seems that the tissue can be eaten.

Moreover, it is not clear in the introduction which is the advantage of these biodegradable polymers over the claimed solution and emulsions of the first sentence in relation to both cosmetics and nutraceutics.

Author Response

It is now clear the relationship between “beauty from within” and the development of green materials for cosmetics and nutraceutical products.

Thank you for appreciating our work

However, it is not still clear which is the relationship between carrier tissues and nutraceuticals. For instance, the first sentence in the abstract “The present review was conceived to explain the possibility of realizing novel nanostructured tissues containing functional molecules to be commercialized as solid product (without using emulsifiers and preservatives) for cosmeceutical and nutraceutical applications”. From this sentence, it seems that the tissue can be eaten.

This significant aspect was clarified inserting this sentence in the introductory part: "This concept can be applied to both skin or buccal mucosa. In the latter case food grade or edible materials should be selected as tissue carriers for preparing a nutraceutical product with a controlled release kinetic and a selected end of life". Thank you for suggesting this clarification.

Moreover, it is not clear in the introduction which is the advantage of these biodegradable polymers over the claimed solution and emulsions of the first sentence in relation to both cosmetics and nutraceutics.

At the end of the introductory part we have inserted the sentence :"Moreover, in both cosmeceutical and nutraceutical applications, the exploitation of a fast but controlled release kinetic can allow active agents to be released on the skin/mucosa very efficiently thanks to their homogeneous dispersion in the nanostructured tissue. "

Thank you very much for your very precious suggestions