Drug Delivery Systems Utilizing Essential Oils and Their Compounds—A Promising Approach to Fight Pathogens
, Maja Świerczyńska 1, Amelia Wieczorek 1, Piotr Baszuk 2, Iwona Wojciechowska-Koszko 1, Monika Sienkiewicz 3,* and Paweł Kwiatkowski 1,*
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe review summarises the knowledge gained over the last 15 years on the delivery systems that may make it possible to use essential oils in medicine, in spite of their unfavourable properties. The review is logically structured and discusses valuable literature so it may be of intrest to the readers of the journal.
Major comments:
1. In chapter 4 (Search results) Figure 2 shows the number of hits in the literature search and Figure 3 is supposed to show the same but with the hits sorted by year. However, the data in the two figures are not consistent, e.g. in case of „zeolite” AND „essential oils” Fig. 2 shows 8 hits and 1 hit including the „medical application” term, but in Fig. 3 the number of hits are 11 and 2 (summing up the number of papers in each year); in case of „PLGA” AND „essential oils” 10 and 0 hits vs 16 and 0 hits; in case of „zein” AND „essential oils” 28 and 6 hits vs 59 and 11. Otherwise, it would be good to interpret Figure 2 and draw a conclusion.
2. In relation to the first comment, in case of „PLGA AND essential oils AND medical application” 0 hits were found but in chapter 5.8 two articles are mentioned with medical application [93] and [94], so it seems that using the term „medical application” does not always lead to finding the appropriate literature. But you have obviously also interpreted literature from the previous, larger hits, so in chapter 4 you should write down what kind of literature you finally discussed in chapter 5.
3. The proportions of subchapters in Chapter 5 are not in line with the amount of literature found. In terms of medical use, based on the number of references, nanoemulsions have the greatest importance as delivery systems. Despite this, this is almost the shortest part of the review with about 7 cited references, but liposomes have a similarly short subchapter with a total of 4 cited references. This is particularly striking when compared to the length of the subchapters on zeolites and PLGA and the number of articles found on their topic.
4. Figure 4 is not mentioned anywhere in the text.
Minor comments:
reference [10] is referred to as Gosh et al. but in the list of references the author’s list starts with the name Navani – actually, the names of the authors are totally mixed up and incomplete in this reference and there are other references with the same problem (e.g. [31], [60]. In addition, the doi numbers are given in two different ways in the references. A uniform format for references would be desirable.
line 72 – citotoxicity instead of citotoxic
line 125 – beta-caryophyllene is a sesquiterpene not a monoterpene
In Table 1 – all solubility in water should be written in the same unit (e.g. mg/L) so the menthol’s unit should be changed
Fig. 1. in the upper middle square administration instead of administering
line 402 – not ref [93] should be cited here instead of [92]?
line 409 –„their loading capacity is quite low and that their production is high” – what do you mean on „that their production is high”? It does not make sence in this context.
Author Response
Dear Reviewer 1,
Thank you for a helpful review of our manuscript. All comments helped us to clarify our results and to improve the readability of the article. Your suggestions have been incorporated as appropriate into the revised version of the manuscript. The manuscript has been modified, reorganized and completed. Please find below our answers. We appreciate your contribution that helps improving the manuscript.
The review summarizes the knowledge gained over the last 15 years on the delivery systems that may make it possible to use essential oils in medicine, in spite of their unfavorable properties. The review is logically structured and discusses valuable literature so it may be of interest to the readers of the journal.
Major comments:
- In chapter 4 (Search results) Figure 2 shows the number of hits in the literature search and Figure 3 is supposed to show the same but with the hits sorted by year. However, the data in the two figures are not consistent, e.g. in case of „zeolite” AND „essential oils” Fig. 2 shows 8 hits and 1 hit including the „medical application” term, but in Fig. 3 the number of hits are 11 and 2 (summing up the number of papers in each year); in case of „PLGA” AND „essential oils” 10 and 0 hits vs 16 and 0 hits; in case of „zein” AND „essential oils” 28 and 6 hits vs 59 and 11. Otherwise, it would be good to interpret Figure 2 and draw a conclusion.
Answer: Corrected.
- In relation to the first comment, in case of „PLGA AND essential oils AND medical application” 0 hits were found but in chapter 5.8 two articles are mentioned with medical application [93] and [94], so it seems that using the term „medical application” does not always lead to finding the appropriate literature. But you have obviously also interpreted literature from the previous, larger hits, so in chapter 4 you should write down what kind of literature you finally discussed in chapter 5.
Answer: The additional studies were added due to their relevance and interest in our paper, for some unknown reason they were not found by the primary search. We added information about it to specify why they appear in the text further below.
- The proportions of subchapters in Chapter 5 are not in line with the amount of literature found. In terms of medical use, based on the number of references, nanoemulsions have the greatest importance as delivery systems. Despite this, this is almost the shortest part of the review with about 7 cited references, but liposomes have a similarly short subchapter with a total of 4 cited references. This is particularly striking when compared to the length of the subchapters on zeolites and PLGA and the number of articles found on their topic.
Answer: Added additional content to nanoemulsion and liposomes sections.
- Figure 4 is not mentioned anywhere in the text.
Answer: The mention was added in Chapter 6
Minor comments:
reference [10] is referred to as Gosh et al. but in the list of references the author’s list starts with the name Navani – actually, the names of the authors are totally mixed up and incomplete in this reference and there are other references with the same problem (e.g. [31], [60]. In addition, the doi numbers are given in two different ways in the references. A uniform format for references would be desirable.
Answer: Corrected
line 72 – citotoxicity instead of cytotoxic
Answer: Corrected.
line 125 – beta-caryophyllene is a sesquiterpene not a monoterpene
Answer: Corrected.
In Table 1 – all solubility in water should be written in the same unit (e.g. mg/L) so the menthol’s unit should be changed
Answer: Corrected.
Fig. 1. in the upper middle square administration instead of administering
Answer: Corrected.
line 402 – not ref [93] should be cited here instead of [92]?
Answer: Corrected
line 409 –„their loading capacity is quite low and that their production is high” – what do you mean on „that their production is high”? It does not make sence in this context.
Answer: Added missing “cost” to make the sentence clear.
Moreover, minor linguistic errors have been corrected.
Thank you very much for your valuable suggestion.
Sincerely Yours,
Authors
Reviewer 2 Report
Comments and Suggestions for AuthorsThe article reports on a review about drug delivery systems that have been used for essential oils delivery for medical applications.
The suggestions are the following:
- The title of the manuscript does not correspond with the content. The presented examples are not exclusively related to bacteria control.
- Abstract. It is not clear the relation between the topic of the review and the use of essential oils.
- Lines 20-21. The list contains mostly materials instead of methodologies.
- Lines 22-24. It is not clear if the lack of clinical trials corresponds to drug delivery or the use of essential oils.
- Line 46. Write Escherichia coli in cursive.
- It is suggested to include a list of essential oil components, their biological activity and main plant sources.
- Lines 84-86. Include the relation between the objective of the work with the essential oil topic.
- Instead of the word “alpha” include the Greek word.
- Information given in Table 1 should be analyzed in the text.
- Lines 110-111. Include the compounds used as fragrances in reference 31.
- Include the desired range of values for the required properties of compounds used for medical formulations in comparison with essential oil components.
- Lines 118-120. If essential oil components have a low absorption rate from the digestive tract because of their low water solubility, why do most reported effects come from the digestive system?
- Lines 145-146. Why p-cymene is obtained by oxidation process? This compound does not contain oxygen.
- Check the title of Figure 3 because the list of key words used for article search does not include drug delivery system. Medical application does not necessarily correspond to drug delivery.
- Lines 181-184. Include the references related to zeolite uses as drug delivery systems and specify the type of used zeolites.
- Line 233. What do the authors mean with “primary EOC” and “plant extract”? The EOC is extracted from the plant.
- Lines 242-242. Which are the numerous studies that “have shown that encapsulating EOs in liposomes helps extend their antimicrobial, antioxidant, and cytotoxic properties”?
- Line 312. Specify if the sample is cellulose or EO.
- Line 362. Include the meaning of MIC.
- Line 368. Include the meaning of PLGA.
- Figure 4. Include the type of zeolites that have bactericidal and cytotoxic properties. Which systems have been tested in clinical trials?
- Conclusions section should present an analysis of Figure 4, making a comparison of the systems that were reported in the manuscript of EO delivering.
Author Response
Dear Reviewer 2,
Thank you for a helpful review of our manuscript. All comments helped us to clarify our results and to improve the readability of the article. Your suggestions have been incorporated as appropriate into the revised version of the manuscript. The manuscript has been modified, reorganized and completed. Please find below our answers. We appreciate your contribution that helps improving the manuscript.
The article reports on a review about drug delivery systems that have been used for essential oils delivery for medical applications.
The suggestions are the following:
- The title of the manuscript does not correspond with the content. The presented examples are not exclusively related to bacteria control.
Answer: Corrected.
- Abstract. It is not clear the relation between the topic of the review and the use of essential oils.
Answer: Corrected
- Lines 20-21. The list contains mostly materials instead of methodologies.
Answer: Corrected.
- Lines 22-24. It is not clear if the lack of clinical trials corresponds to drug delivery or the use of essential oils.
Answer: Specified as to the essential oils, corrected.
- Line 46. Write Escherichia coli in cursive.
Answer: Corrected.
- It is suggested to include a list of essential oil components, their biological activity and main plant sources.
Answer: Corrected, added to the Table 1.
- Lines 84-86. Include the relation between the objective of the work with the essential oil topic.
Answer: Corrected
- Instead of the word “alpha” include the Greek word.
Answer: Corrected.
- Information given in Table 1 should be analyzed in the text.
Answer: Corrected
- Lines 110-111. Include the compounds used as fragrances in reference 31.
Answer: Corrected
- Include the desired range of values for the required properties of compounds used for medical formulations in comparison with essential oil components.
Answer: Could the Reviewer specify what desired values for the properties refer to? We added a mention with a source of it in the introduction. The source contains desired MIC values for example, but we are not sure if that’s what you intended.
- Lines 118-120. If essential oil components have a low absorption rate from the digestive tract because of their low water solubility, why do most reported effects come from the digestive system?
Answer: A clarifying sentence has been added.
- Lines 145-146. Why p-cymene is obtained by oxidation process? This compound does not contain oxygen.
Answer: Corrected, p-cymene is the result of degradation, but not oxidation.
- Check the title of Figure 3 because the list of key words used for article search does not include drug delivery system. Medical application does not necessarily correspond to drug delivery.
Answer: We applied the Reviewer suggestion and ran the search again, which retrieved the same results.
- Lines 181-184. Include the references related to zeolite uses as drug delivery systems and specify the type of used zeolites.
Answer: Corrected by adding the specific zeolite types.
- Line 233. What do the authors mean with “primary EOC” and “plant extract”? The EOC is extracted from the plant.
Answer: Corrected.
- Lines 242-242. Which are the numerous studies that “have shown that encapsulating EOs in liposomes helps extend their antimicrobial, antioxidant, and cytotoxic properties”?
Answer: Corrected.
- Line 312. Specify if the sample is cellulose or EO.
Answer: Corrected, specified to cellulose
- Line 362. Include the meaning of MIC.
Answer: Corrected.
- Line 368. Include the meaning of PLGA.
Answer: Corrected.
- Figure 4. Include the type of zeolites that have bactericidal and cytotoxic properties. Which systems have been tested in clinical trials?
Answer: We thank the Reviewer for this suggestion. Figure 4 shows the main advantages and disadvantages of different drug delivery systems. We believe that this suggestion is correct, although, in order not to distort the meaning of the figure, we have decided to add this information to the chapter on zeolites.
In addition, as suggested by the Reviewer, we decided to search for clinical trials using natural compounds and carriers. For this purpose, we used the clinicaltrials.gov database. The search revealed 1 existing study of unknown status, which analysed the bioavailability of, among others, liposomes loaded with coenzyme Q10. As it does not indicate significant microbiological results, we decided not to cite them in our manuscript. We hope that this will satisfy the Reviewer.
- Conclusions section should present an analysis of Figure 4, making a comparison of the systems that were reported in the manuscript of EO delivering.
Answer: Added a section comparing the delivery systems.
Moreover, minor linguistic errors have been corrected.
Thank you very much for your valuable suggestion.
Sincerely Yours,
Authors
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsThe authors have corrected the manuscript as suggested so I have no further comments.
