Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The work by Santonocito et al. tries to elucidate the effect of the oil phase in the application of nanostructured lipid carriers. However, the work is written in such a way that makes very difficult to extract the conclusions. Specific points:

-Results and discussion section style is more suitable for a review paper than for a research paper. Many information about general aspects is included but the discussion of the results is scarce.

-There is not almost discussion, most of the text is mainly presentation of the results.

-Physico-chemical/molecular aspects should be considered

-Figure 3 is not cleat at all

Comments on the Quality of English Language

 Moderate editing of English language required

Author Response

Reviewer 1

The work by Santonocito et al. tries to elucidate the effect of the oil phase in the application of nanostructured lipid carriers. However, the work is written in such a way that makes very difficult to extract the conclusions. Specific points:

-Results and discussion section style is more suitable for a review paper than for a research paper. Many information about general aspects is included but the discussion of the results is scarce.

-There is not almost discussion, most of the text is mainly presentation of the results.

Answer

We would like to thank the reviewer for reviewing our manuscript.

According to the “Guidelines for Reviewers” published by MDPI, reviewers should consider the following guidelines: “Please ensure your comments are detailed so that the authors may correctly understand and address the points you raise”; “Please maintain a neutral tone and focus on providing constructive criticism that will help the authors improve their work.“

Unfortunately, the reviewer did not provide us with detailed comments that could help us to improve our work. The reviewer did not explain why the discussion is scarce. In the “results and discussion” section, first we reported the results of experiments performed to evaluate a given technological parameter and then we analyzed such results comparing them to existing literature data. For instance, after reporting the results of experiments performed to evaluate the occlusion factor (F) of the emulsions under investigation, we discussed the obtained results making the following comments “These results support the hypothesis that the occlusive properties of O/W emulsions could be affected by the amount of oils used for their preparation [70]. When BMTZ-loaded NLC were incorporated into the emulsions, F values decreased regardless of the lipid phase ratio, suggesting that BMTZ-loaded NLC could alter the emulsion structure making it more permeable to water. Previous differential scanning calorimetry studies [45] pointed out that BMTZ-loaded NLC had low crystallinity that was attributed to their high percentage of liquid lipid. As reported in the literature [49,71], lipid nanoparticles with low crystallinity could not be expected to provide a significant enhancement of the occlusion factor.”

Therefore, it is unclear what we are supposed to amend to improve the discussion of our results.

 

-Physico-chemical/molecular aspects should be considered

Answer

In this work, we evaluated technological and sensory properties of O/W emulsions containing different lipid phase ratios as vehicles for bemotrizinol loaded NLC. We assessed the following physico-chemical properties of the investigated formulations: pH. stability, viscosity, occlusion factor, spreadability, in vitro bemotrizinol release.  As we did not perform experiments that allowed us to evaluate molecular aspects, we did not discuss such aspects. 

 

-Figure 3 is not cleat at all

Answer

The reviewer does not explain why Figure 3 is not clear. As we do not understand why the reviewer think that Figure 3 is not clear, unfortunately we do not know how we are supposed to make it clearer. We would like to highlight that other reviewers did not raise any criticism about this figure.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The authors report data on a broad spectrum sunscreen agent inside nanostructured lipid carriers and these are formulated in the O/W emulsion. The paper contains good characterization data and also sensory evaluation data. Some discussion could be improved:

(a) comment more on the possible range of lipid phase ratio, such as what is lowest and highest possible values

(b) comment on significance of zeta potential for stability

(c) Is there significance to the subtle variations in the composition of lipid phase A in Table 1?

(d) What is Komipur 100 perservative? What type of chemical?

(e) I think sufficit should be sufficient.

(f) line numbers in Table 1 are over writing the text

(g) what is the chemical structure of bemotrizinol?

Author Response

Reviewer 2

The authors report data on a broad spectrum sunscreen agent inside nanostructured lipid carriers and these are formulated in the O/W emulsion. The paper contains good characterization data and also sensory evaluation data. Some discussion could be improved:

(a) comment more on the possible range of lipid phase ratio, such as what is lowest and highest possible values

Answer

We would like to thank the reviewer for the valuable comments. To comply with the reviewer’s request, we inserted in the text the following sentences: “Generally, the lipid phase content in cosmetic O/W emulsions ranges between 10% w/w and 50% w/w, being 75% w/w the maximum theoretical value.”

(b) comment on significance of zeta potential for stability

Answer

To comply with the reviewer’s request, we inserted the following comments on significance of zeta potential for lipid nanoparticle stability: “Generally, ζ-potential values greater than 30 mV, as absolute value, are regarded as suitable to obtain stable colloidal suspensions. Despite of ζ-potential values lower than 30 mV, BMTZ loaded NLC showed good stability after storage for two months at room temperature. Such good stability was attributed to the presence of long polyoxyethylene chains of the surfactant oleth-20 on the nanoparticle surface, which could provide a steric stabilization [45].

(c) Is there significance to the subtle variations in the composition of lipid phase A in Table 1?

Answer

To increase the lipid phase percentage from 12 to 16 % w/w, we increased the percentage of each component of phase A to the same extent to maintain the same quantitative ratio among components. Therefore, the slight variations in the composition of phase A could not be regarded as significant.

 (d) What is Komipur 100 perservative? What type of chemical?

Answer

As reported in the “materials” section, Kemipur 100 is a commercial name for the preservative imidazolidinyl urea.

(e) I think sufficit should be sufficient.

Answer

Quantum sufficit is a Latin term meaning "as much as is sufficient". This term is commonly used in medicine, pharmacology and pharmaceutical field as quantity specification.

(f) line numbers in Table 1 are over writing the text

Answer

We apologize for the inconvenient. Unfortunately, in our version of the manuscript, we do not observe any line numbers overwriting in Table 1. Therefore, we guess that this inconvenient could be attributed to a different software visualization. Unfortunately, as this inconvenient does not occur in our visualization of the manuscript, we are not able to correct it. However, we moved Table 1 on the left side hoping that, in this way, line numbers do not overwrite the text.

(g) what is the chemical structure of bemotrizinol?

Answer

As reported in the introduction, bemotrizinol is a triazine derivative. To provide the reader with information about the chemical structure of bemotrizinol, we inserted in the text the chemical name of bemotrizinol, that is to say bis-ethylhexyloxyphenol methoxyphenyl triazine.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The article entitled “Effects of lipid phase content on the technological and sensory  properties of O/W emulsions containing bemotrizinol loaded nanostructured lipid carriers” is investigated the effects of using different percentages of lipid phase having the same composition on the technological properties  (viscosity, spreadability, occlusion factor, stability, in vitro release and SPF value) of O/W emulsions in which BMTZ-loaded NLC were incorporated. Authors are encouraging to consider the following comments and suggestion for further refinement of their work

1.     Authors should add the mathematic data in the abstract such as Particle size, viscosity, pH, % loading  etc . for a clear understanding the article outcome.

2.     Authors have mentioned “ In addition, several studies have highlighted the ability of SLN and NLC to incorporate organic UV-filters, thus supporting the feasibility of using these nanocarriers to develop sunscreen formulations”, Provide the detail mechanism of the and advantages of the SLN and NLC for the sunscreen over the other lipid nanoparticles

3.     Authors mention that “In a previous work of ours, BMTZ was incorporated into various types of NLC and the technological properties of O/W emulsions containing different percentages of optimized BMTZ-loaded NLC were evaluated”. Please provide a correct reference and briefly mention the outcome of the previous research result and how the current study is different from the existing data.

4.     Provide a clear Novelty statement for the research.

5.     Authors should provide a explanation in which basis the concentration of the composition is selected. If it is selected based on the previous research, provide a brief of the data.

6.     Provide the process parameter detail like vigorous stirring rpm and time

7.     What id the pH of the receiving phase in the release study

8.     It is  a suggestion to the authors , rather writing  “ Due to the nature of the study, the local Ethical Committee declared that no approval was required” , they can change the statement as “sunscreens are considered “over the counter” (OTC) drugs and are considered under the FDA's Final Rule 2011 and the Sunscreens Innovation Act 2014 so  The FDA demands sunscreens are tested in 10 human volunteers , as for that only consent form is sufficient rather a local Ethical Committee approval.”

9.     Change the table 3 punctuation from “,” to “.” For the all the data

10. Provide the SD data for the fig 1 and 2  with high resolution image

11. Authors should discuss the results with more details. And rewrite the conclusion

12. What is the future direction and the limitation of the current of the research?

13. The English language needed a professional revision

Comments on the Quality of English Language

Moderate grammatical editing is needed

Author Response

Reviewer 3

The article entitled “Effects of lipid phase content on the technological and sensory  properties of O/W emulsions containing bemotrizinol loaded nanostructured lipid carriers” is investigated the effects of using different percentages of lipid phase having the same composition on the technological properties  (viscosity, spreadability, occlusion factor, stability, in vitro release and SPF value) of O/W emulsions in which BMTZ-loaded NLC were incorporated. Authors are encouraging to consider the following comments and suggestion for further refinement of their work

1. Authors should add the mathematic data in the abstract such as Particle size, viscosity, pH, % loading etc . for a clear understanding the article outcome.

Answer

We would like to thank the reviewer for the valuable comments.

We agree with the reviewer that the addition of numeric values of the investigated parameters would be useful for the reader but according to the “Instructions for Authors” published by MPDI, “The abstract should be a total of about 200 words maximum.” Therefore, having such a low number of words available to describe the aim and the results of our work, we could not insert the numeric values of all investigated parameters for all formulations we analyzed.

 

2. Authors have mentioned “ In addition, several studies have highlighted the ability of SLN and NLC to incorporate organic UV-filters, thus supporting the feasibility of using these nanocarriers to develop sunscreen formulations”, Provide the detail mechanism of the and advantages of the SLN and NLC for the sunscreen over the other lipid nanoparticles.

Answer

To comply with the reviewer request, we inserted in the text the following sentences: “In particular, due to the presence of solid lipids in their core, SLN and NLC could act as physical sunscreens mostly reflecting UV-radiation.  Therefore, SLN and NLC could act in synergy with organic UV-filters to improve SPF values of sunscreen products [36-39].”

 

3. Authors mention that “In a previous work of ours, BMTZ was incorporated into various types of NLC and the technological properties of O/W emulsions containing different percentages of optimized BMTZ-loaded NLC were evaluated”. Please provide a correct reference and briefly mention the outcome of the previous research result and how the current study is different from the existing data.

Answer

We apologize for the incorrect reference that we amended. In the introduction, we explained that “These formulations showed interesting technological characteristics, such as low BMTZ release from the vehicle, good stability and about a 20% increase of in vitro SPF values in comparison with formulations containing the same percentage of free BMTZ.” To highlight the differences between the current study and the previous research of ours, we amended the above-mentioned sentence as follows: “These formulations, containing the same percentage of lipid phase, showed interesting technological characteristics, such as low BMTZ release from the vehicle, good stability and about a 20% increase of in vitro SPF values in comparison with formulations containing the same percentage of free BMTZ.”

 

4. Provide a clear Novelty statement for the research.

Answer

To comply with the reviewer request, we inserted in the introduction the following sentence: “To the best of our knowledge, the effects of different lipid phase ratios on the technological properties of O/W emulsions used as vehicle for UV-filter loaded lipid nanoparticles have not been fully explored.”

5. Authors should provide a explanation in which basis the concentration of the composition is selected. If it is selected based on the previous research, provide a brief of the data.

Answer

The percentages of lipids were chosen taking into account their properties, such as spreadability and oiliness, to obtain O/W emulsions with good technological and sensory properties. The percentage of emulsifier was chosen according to the manufacturer recommendations. All other ingredients were added in the percentages commonly used in cosmetic O/W emulsions.

 

6. Provide the process parameter detail like vigorous stirring rpm and time

Answer

To comply with the reviewer’s request, we inserted the requested details by adding the following information: “the water phase was poured into the oil phase under stirring for 90 sec at 5.000 rpm”.

 

7. What id the pH of the receiving phase in the release study

Answer

The receiving phase had a pH value of 6.5. We inserted this information in the text.

 

8. It is a suggestion to the authors , rather writing  “ Due to the nature of the study, the local Ethical Committee declared that no approval was required” , they can change the statement as “sunscreens are considered “over the counter” (OTC) drugs and are considered under the FDA's Final Rule 2011 and the Sunscreens Innovation Act 2014 so  The FDA demands sunscreens are tested in 10 human volunteers , as for that only consent form is sufficient rather a local Ethical Committee approval.”

Answer

We would like to thank the reviewer for the suggestion. We work in Europe and we carried out this experimental work according to the European legislation that classifies sunscreen agents as cosmetics. As USA legislation on sunscreen agents is different from the European one, we reported the statements required by the legislation in force in our country.

 

9. Change the table 3 punctuation from “,” to “.” For the all the data

Answer

As requested, we changed the punctuation in Table 3.

 

10. Provide the SD data for the fig 1 and 2 with high resolution image.

Answer

In Fig. 1, we reported the relationship between two parameters, viscosity and spreadability, whose standard deviation is reported in Table 3. In Fig. 1, we omitted standard deviations of each data for clarity as some standard deviations overlapped making data visualization unclear. Therefore, we specified in the legend of Fig.1, that “data S.D. was omitted for clarity”. To prepare Fig. 2, we chose a type of graph that did not allow us to report standard deviation data. We agree with the reviewer that S.D. would be useful to analyze the results illustrated in Fig.2. Therefore, we changed the type of graph and inserted S.D. data. We specified in the legend of Fig. 2 that S.D. was not reported for in silico data because this data was generated by a software.

Fig. 1 and 2 were prepared using the Excel software. As requested by the reviewer, we tried to improve resolution. 

 

11. Authors should discuss the results with more details. And rewrite the conclusion

Answer

We discussed the results of our work by formulating only rational hypothesis that could be supported by the obtained data and the existing literature data that, in our opinion, were the most relevant. Therefore, it is unclear what details we are supposed to add. Similarly, in the conclusions, after illustrating the background of this work, we summarized the main results and their potential use in formulating sunscreen products.  The reviewer asked us to rewrite the conclusions without providing any detail that allowed us to understand how we are supposed to rewrite the conclusions. According to the “Guidelines for Reviewers” published by MDPI, reviewers should consider the following guidelines: “Please ensure your comments are detailed so that the authors may correctly understand and address the points you raise”; “Please maintain a neutral tone and focus on providing constructive criticism that will help the authors improve their work.“

Unfortunately, as the reviewer did not explain how we should rewrite the conclusions, we could not amend this section.

12. What is the future direction and the limitation of the current of the research?

Answer

We planned further studies to evaluate the effects of different lipid phase compositions on the technological and sensory properties of O/W emulsions as vehicles for bemotrizinol loaded NLC. In addition we planned to evaluate the feasibility of incorporating simultaneously bemotrizinol and octyl methoxycinnamate, a widely used UV-filter, into NLC to assess their impact on SPF values. The most promising formulation will be tested to assess its SPF value in vivo because the results of in vitro tests have to be confirmed by in vivo evaluation.

 

13. The English language needed a professional revision

Answer

English was revised by an English mother tongue.

Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

The manuscript investigates the effect of of lipid phase content on the technological and sensory properties of O/W emulsions containing bemotrizinol loaded nanostructured lipid carriers. The paper is well-written and structured and the conclusions are supported by the obtained results. Comment to the authors:

There is highlighted text in the paper. Please correct.

Table 1 needs better formating.

 

Author Response

The manuscript investigates the effect of of lipid phase content on the technological and sensory properties of O/W emulsions containing bemotrizinol loaded nanostructured lipid carriers. The paper is well-written and structured and the conclusions are supported by the obtained results. Comment to the authors:

 

There is highlighted text in the paper. Please correct.

Answer

We would like to thank the reviewer for reviewing our manuscript.  As requested, we removed the yellow highlighting.

 

Table 1 needs better formating.

Answer

We reduced the size of the character in Table 1. We hope that now Table 1 is properly formatted.

Reviewer 5 Report

Comments and Suggestions for Authors

Dear authors, 

Thank you for this very thorough and interesting study on the use of NSLC in o/w emulsions for the sunscreen agent bemotrizinol. You have done careful and comprehensive work in preparing and characterizing the formulation. There is great interest in the use of NSLC in emulsions for topical administration, so your work may provide useful guidance and perspective.

Intro: please give a rationale for the choice of BMTZ as a sunscreen, including its mechanism of action.

Methods:

2.8 Please describe and list the source of the cellulose membranes used in the Franz cells and their average molecular weight cutoff .  One reference (from1989) is used to justify the choice of membrane and this is not well representative of human skin. However, if the only purpose is to have a semipermeable membrane for free drug to cross, it is acceptable if the MWCO is indicated.  

2.9 Kindly explain briefly the "erythemal effect" and its units.

2.10 Sensory Evaluation and Fig. 3. Please indicate the graphing software used and add a brief aid to the reading the graphs. Table 2 indicates 4 point scales but the graphs have a scale of 0-50.  Why were only female evaluators used, and in such a limited age range (30-46)?

Results:

The following points are intended to clarify a few points for the readers:

1. Table 3 indicates a reduction in the value of F (occulsion factor) when NSLCs are incorporated into the o/w emulsion. The authors suggest (line343-344) that the relationship between the NSLC and the emulsion alters the emulsion structure. This is one of the most interesting concepts in the paper. The methods indicate TEM was performed, however, no TEM results are presented. It would be of interest to see if the altered structure could be visualized to further explain this result. The concept has implications for other topical preparations containing NSLCs.

lines 377-385: Please explain the BASF sunscreen simulator further. For example, define the "erythemal weighted solar radiation intensity" and the "areas" that are being compared.

Fig 2: SPF values of 6-8 are reported, which are rather low. Do the authors have any propositions to increase this value for BMTZ containing sunscreens, particularly since increasing the NSLC load resulted in less preferable sensory features?

Fig 3: The legend should explain the axes and numbers, since this is not a very common sort of graph. Why were these parameters grouped in this way in a, b, and c? The symbols in the graphic legend are too small and too similar. Consider using different symbols for better clarity.

References: Several reference citations have titles in all capital letters (for example #65), so please correct those with the journal-consistent style.

#65: The original method was cited (1979) but please also include more recent examples of its application

Comments on the Quality of English Language

The quality of English is acceptable. No concerns.

Author Response

Dear authors,

Thank you for this very thorough and interesting study on the use of NSLC in o/w emulsions for the sunscreen agent bemotrizinol. You have done careful and comprehensive work in preparing and characterizing the formulation. There is great interest in the use of NSLC in emulsions for topical administration, so your work may provide useful guidance and perspective.

 

Intro: please give a rationale for the choice of BMTZ as a sunscreen, including its mechanism of action.

Answer

We would like to thank the reviewer for the valuable comments.

To comply with the reviewer’s request, we inserted in the introduction, at line 63, the following sentences:

“BMTZ was chosen as broad-spectrum UV-filter because of its photostability, safety and ability to absorb both UV-B and UV-A rays converting the absorbed UV energy into less harmful forms [40-44]. In addition to absorbing UV radiation, BMTZ could form a thin film on the skin surface because of its poor ability to penetrate the skin.  Such that reflects and scatters UV rays. This physical barrier helps to further block UV radiation from reaching the deeper layers of the skin.”

Methods:

2.8 Please describe and list the source of the cellulose membranes used in the Franz cells and their average molecular weight cutoff.  One reference (from1989) is used to justify the choice of membrane and this is not well representative of human skin. However, if the only purpose is to have a semipermeable membrane for free drug to cross, it is acceptable if the MWCO is indicated. 

Answer

We apologize for our oversight.  In the revised version of the manuscript, we inserted in the “materials” section all data about the cellulose membranes we used, reporting the following information: “Regenerated cellulose membranes (Spectra/Por CE; Mol. Wt. Cut off 3000) were bought from Spectrum (Los Angeles, CA, USA).

 

2.9 Kindly explain briefly the "erythemal effect" and its units.

Answer

As reported in the manuscript, EE(λ) is the erythemal effect of the radiation with wavelength λ, namely the ability of UV radiations with a given wavelength in the range 290.320 nm to induce an erythema.  Sayre et al. (ref. 65) defined EE(λ) as erythemal efficiency spectrum and provided a Table where the normalized product function used in the calculation of SPF data is reported.  No units have been reported in the work by Sayre at al.

 

2.10 Sensory Evaluation and Fig. 3. Please indicate the graphing software used and add a brief aid to the reading the graphs. Table 2 indicates 4 point scales but the graphs have a scale of 0-50.  Why were only female evaluators used, and in such a limited age range (30-46)?

Answer

As requested, we indicated the graphing software and provided a description of the type of graph we constructed. Table 2 indicates five-point scales (from 1 to 5) for each parameter, therefore the maximum score achievable for each parameter was 50 (5 X 10 panelist). To clarify these points, we inserted the following sentences: “For each attribute in each phase, the sum of the scores (from 1 to 5) assigned by each panelist was performed and reported in radar charts (Excel for Windows ver 11, Microsoft Corporation, Redmond, USA) in which each axis indicated the scores assigned by panelists for a given parameter. For each parameter the minimum score was 10 and the maximum was 50.”

To perform sensory evaluations, generally we recruit adults (regardless of sex) in the age range 20-60. Some men were asked to participate but they were not available. Indeed, in our experience, men are less likely to test cosmetics, even sunscreen products. Therefore, coincidentally, only women participated in the study. There was no specific reason to use a panel consisting only of women in the age range 30-46.

 

Results:

The following points are intended to clarify a few points for the readers:

Table 3 indicates a reduction in the value of F (occulsion factor) when NSLCs are incorporated into the o/w emulsion. The authors suggest (line343-344) that the relationship between the NSLC and the emulsion alters the emulsion structure. This is one of the most interesting concepts in the paper. The methods indicate TEM was performed, however, no TEM results are presented. It would be of interest to see if the altered structure could be visualized to further explain this result. The concept has implications for other topical preparations containing NSLCs.

Answer

TEM analyses were performed on unloaded and BMTZ-loaded NLC. We did not perform TEM analyses on O/W emulsions incorporating NLC. However, we agree with the reviewer that it would be interesting to analyze the structure of the emulsions resulting from NLC incorporation. In the present study, we aimed to evaluate the macroscopic and sensory properties of emulsions prepared using different lipid phase ratios and containing NLC loading BMTZ. In future studies, we have planned to investigate the effects of incorporating different concentration of NLC into emulsions with different composition to analyze the structure of the resulting formulations at microscopic level.

 

 

lines 377-385: Please explain the BASF sunscreen simulator further. For example, define the "erythemal weighted solar radiation intensity" and the "areas" that are being compared.

Answer

As requested, to better explain the BASF sunscreen simulator, we modified the text as follows: “This software is based on the concept that, according to Sayre et al. [65], SPF can be conceptualized as the ratio of areas under the transmittance vs wavelength plot taking into account the erythemal weighted UV of solar radiation, which has been defined as a function the wavelength, the irradiance and the erythemal weighting function.

 

Fig 2: SPF values of 6-8 are reported, which are rather low. Do the authors have any propositions to increase this value for BMTZ containing sunscreens, particularly since increasing the NSLC load resulted in less preferable sensory features?

Answer

In the past (see reference 36), we prepared lipid nanoparticles loading simultaneously an UV-B filter (octyl methoxycinnamate, OMC) and an UV-A filter (butyl methoxydibezoyl methane, BMBM). As OMC is a lipophilic liquid, its incorporation into the nanoparticles allowed a greater loading of BMBM. We have planned to apply this strategy incorporating both OMC and BMTZ into NLC to obtain formulations with higher SPF values.

 

Fig 3: The legend should explain the axes and numbers, since this is not a very common sort of graph. Why were these parameters grouped in this way in a, b, and c? The symbols in the graphic legend are too small and too similar. Consider using different symbols for better clarity.

Answer

The graphs reported in Fig. 3 are often used to report data from sensory evaluations on products such as cosmetics, food etc. As explained in the legend of Fig. 3, the parameters were grouped according to the different phases of the sensory evaluation, namely a) before and during product pick-up, b) during product rub-in, 3) after feel. However, for a better comprehension of these graphs, we split Fig. 3 in three figures and we enlarged each figure using different symbols. Therefore, Fig. 3a became Fig. 3, Fig. 3b became Fig.4 and Fig. 3c became Fig. 5. As requested, we reported in the legend of each figure the explanation of axes and numbers as follows: “Each axis indicates the scores assigned by panelists for a given parameter. Data were reported as the sum of all scores that panelists assigned to a given parameter.” 

 

References: Several reference citations have titles in all capital letters (for example #65), so please correct those with the journal-consistent style.

Answer

We apologize for the inconvenient. We corrected the reference having titles in all capital letters.

 

#65: The original method was cited (1979) but please also include more recent examples of its application

Answer

As requested, we inserted more recent examples of the application of the original method developed by Sayre et al. Therefore, we inserted in the text the following sentence: “Recent examples of SPF determination using the parameters reported by Sayre et al. [65] include the evaluation of in vitro photoprotective effect of the curcumin-loaded emulsion [83] and the UVB-protection performance of proanthocyanidin-rich extracts obtained from Cinnamomum camphora leaves [84].

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Authors did not answer any of my previous comment, and therefore manuscript cannot be recommended for publication

Comments on the Quality of English Language

Language is suitable for a research article

Author Response

Authors did not answer any of my previous comment, and therefore manuscript cannot be recommended for publication

Answer

We answered the reviewer’s previous comments explaining that we were not provided with enough details to understand how we were supposed to improve our manuscript to make the reviewer feel that results were properly discussed and Fig. 3 clarity was improved.

Therefore, we would be grateful if the reviewer could provide us with details to understand how the reviewer believes that results should be discussed properly.

Reviewer 3 Report

Comments and Suggestions for Authors

The article entitled “Effects of lipid phase content on the technological and sensory properties of O/W emulsions containing bemotrizinol loaded nanostructured lipid carriers”  is revised.  Authors are encouraged to consider the following comments and suggestions for further refinement of their work

1.     I understand the word limit constraints set by the journal. However, numerical data of the investigated parameters should be included to enhance clarity and provide essential details for the readers.

2.     Explain the detailed Mechanism of how solid lipids in the core of SLN and NLC reflect the UV radiation with proper reference.

3.     There is already a large number of data available about the effects of different lipid phase ratios on the technological properties of O/W emulsions used as vehicles for UV-filter-loaded lipid nanoparticles… Then how the current research is different from the existing research?

4.     “90 sec at 5.000 rpm” is the rpm correct? or is it 5,000 rpm?

 

5.     Table 3 the pH should be written as 6.3 and 6.4 rather than 6,3 and 6,4

Comments on the Quality of English Language

Need extensive grammatical and punctuation editing 

Author Response

The article entitled “Effects of lipid phase content on the technological and sensory properties of O/W emulsions containing bemotrizinol loaded nanostructured lipid carriers” is revised.  Authors are encouraged to consider the following comments and suggestions for further refinement of their work

1. I understand the word limit constraints set by the journal. However, numerical data of the investigated parameters should be included to enhance clarity and provide essential details for the readers.

Answer

As requested by the reviewer, we inserted numerical data of the investigated parameters. Unfortunately, to comply with the word limit set by the journal, we had to delete the background of the work.

 

2. Explain the detailed Mechanism of how solid lipids in the core of SLN and NLC reflect the UV radiation with proper reference.

Answer

Light reflection by the solid lipids in the core of SLN and NLC is governed by the laws of optics. According to Wissing et al. (Wissing SA, Müller RH. Solid lipid nanoparticles (SLN)--a novel carrier for UV blockers. Pharmazie. 2001 Oct;56(10):783-6. PMID: 11683123) when cetyl palmitate is used as solid lipid to prepare SLN, the crystalline nature of this lipid provides the SLN with “the ability of reflecting and scattering UV radiation on their own”. This information has been inserted in the text of the manuscript at line 423 as follows: “In particular, in this work, lipid nanoparticles were prepared using cetyl palmitate as solid lipid.  According to Wissing and Müller [85], when cetyl palmitate is used as solid lipid to prepare lipid nanocarriers, the crystalline nature of this lipid provides the resulting nanocarriers with the capacity of reflecting and scattering UV light on their own.“

 

3. There is already a large number of data available about the effects of different lipid phase ratios on the technological properties of O/W emulsions used as vehicles for UV-filter-loaded lipid nanoparticles… Then how the current research is different from the existing research?

Answer

Unfortunately, we did not find papers dealing with the evaluation of the effects of different lipid phase ratios (not different lipid phase composition) on the technological and sensory properties of O/W emulsions incorporating lipid nanoparticles loaded with sunscreen agents.

Therefore, we would be grateful if the reviewer could provide us with a list of the most relevant papers published in authoritative scientific journals dealing with this specific topic so as we could compare our work with the existing literature. 

 

4. “90 sec at 5.000 rpm” is the rpm correct? or is it 5,000 rpm?

Answer

We apologize for the typo. We corrected the text reporting 5,000 instead of 5.000.

 

5. Table 3 the pH should be written as 6.3 and 6.4 rather than 6,3 and 6,4

Answer

We apologize for the typo. We corrected pH values in Table 3.

 

The reviewer believes that the manuscript needs extensive grammatical and punctuation editing. As the manuscript has been checked by a native English speaker, we would be grateful if the reviewer could provide us with some examples of the most relevant grammatical mistakes, excluding typos.

Round 3

Reviewer 3 Report

Comments and Suggestions for Authors

Revised 

Comments on the Quality of English Language

Minor editing