Use of paclitaxel carried in solid lipid nanoparticles to prevent peritoneal fibrosis in rats

Filipe M. O. Silva; Priscila O. Carvalho; Elerson C. Costalonga; Rafael Pepineli; Raul C. Maranhão; Irene L. Noronha

doi:10.1371/journal.pone.0268197

Peer Review History

Original SubmissionNovember 29, 2021
7 Jan 2022 Decision Letter - Frank JMF Dor, Editor PONE-D-21-37828USE OF PACLITAXEL CARRIED IN SOLID LIPID NANOPARTICLES TO PREVENT PERITONEAL FIBROSIS IN RATSPLOS ONE Dear Dr. Maranhão, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. ACADEMIC EDITOR: Two expert reviewers have evaluated this MS which is well written and relevant, and the study appears well designed and executed. Some concerns will need to be addressed regarding the validity of the model chosen and how the data would translate into the clinical arena, and a few specific points below. Happy to receive the revised MS for re-evaluation regarding suitability for publication in PlosOne. Please submit your revised manuscript by Feb 21 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. 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Kind regards, Frank JMF Dor, M.D., Ph.D., FEBS, FRCS Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. To comply with PLOS ONE submissions requirements, in your Methods section, please provide additional information on the animal research and ensure you have included details on (1) basic housing and breeding, (2) health monitoring, and (3) efforts to alleviate suffering. 3. As part of your revision, please complete and submit a copy of the Full ARRIVE 2.0 Guidelines checklist, a document that aims to improve experimental reporting and reproducibility of animal studies for purposes of post-publication data analysis and reproducibility: https://arriveguidelines.org/sites/arrive/files/Author%20Checklist%20-%20Full.pdf (PDF). Please include your completed checklist as a Supporting Information file. Note that if your paper is accepted for publication, this checklist will be published as part of your article. 4. Thank you for stating the following financial disclosure: "This study was supported by the State of Sao Paulo Research Support Foundation (FAPESP, Sao Paulo, Brazil, Grant number 2014/03742-0) and by the National Institute of Science and Technology for Complex Fluids of the Ministry of Science, Technology and Innovation of Brazil." Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: No Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 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: Thank you for the opportunity to review this work his is a well designed and conducted study investigating the effect of paclitaxel within lipid nanoparticles to mitigate cholhexidine-gluconate induced peritoneal fibrosis. While this work has been well designed and conducted the key question relates to whether this has clinical relevance. Specifically, there is limited evidence that chlorhexidine-gluconate is a relevant model of PD-induced peritoneal fibrosis see Vlijm et al 2011 Nephron Exp Nephrol. Could the authors comment on why they think that LDE without paclitaxel appears to have 50% as compared with LDE+paclitaxel in mitiigating fibrosis? Please review this sentence "Conversely, the less expensive, home-based PD procedure, which is more often used in poor countries, has important shortcomings". LMIC (lower and middle income countries) may be a more specific description Reviewer #2: This study investigates the effect of intraperitoneal Paclitaxel on the formation of peritoneal fibrosis following exposure to chlorhexidine gluconate. The topic is important as a sizeable number of patients undergoing Peritoneal dialysis must go over to hemodialysis due to the loss of ultrafiltration ability of peritoneum secondary to fibrosis. The study design is adequate and the experiment appears well performed as the authors covered many relevant aspects. This reviewer would have liked to hear briefly about the potential side effects of Paclitaxel or if the results would have been different if the rats had some sort of kidney impairment. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0268197.r001
Revision 1
24 Feb 2022 Author Response Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf - Ok, the requirements were met. 2. To comply with PLOS ONE submissions requirements, in your Methods section, please provide additional information on the animal research and ensure you have included details on (1) basic housing and breeding, (2) health monitoring, and (3) efforts to alleviate suffering. - The additional information on the animal research was included in the Methods section (page 6, lines 121-126). 3. As part of your revision, please complete and submit a copy of the Full ARRIVE 2.0 Guidelines checklist, a document that aims to improve experimental reporting and reproducibility of animal studies for purposes of post-publication data analysis and reproducibility: https://arriveguidelines.org/sites/arrive/files/Author%20Checklist%20-%20Full.pdf (PDF). Please include your completed checklist as a Supporting Information file. Note that if your paper is accepted for publication, this checklist will be published as part of your article. - Ok, the requirements were met. 4. Thank you for stating the following financial disclosure: "This study was supported by the State of Sao Paulo Research Support Foundation (FAPESP, Sao Paulo, Brazil, Grant number 2014/03742-0) and by the National Institute of Science and Technology for Complex Fluids of the Ministry of Science, Technology and Innovation of Brazil." Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. - The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Reply to the reviewers: Beforehand, we would like to deeply thank both Reviewers for their excellent work that helped us to improve our manuscript. Reviewer #1: Thank you for the opportunity to review this work his is a well designed and conducted study investigating the effect of paclitaxel within lipid nanoparticles to mitigate cholhexidine-gluconate induced peritoneal fibrosis. 1. While this work has been well designed and conducted the key question relates to whether this has clinical relevance. Specifically, there is limited evidence that chlorhexidine-gluconate is a relevant model of PD-induced peritoneal fibrosis see Vlijm et al 2011 Nephron Exp Nephrol. - We are now mentioning other PD animal models and justifying our choice of the chlorhexidine-gluconate model for this study (See Introduction section, with two references included, number 23 and 24, page 5, lines 102-111), with further comments in the Discussion section (ref. number 23, page 16, lines 356-359 of the revised manuscript). In respect to the Vlijm et al (2011) paper, which is now being quoted (ref. number 30, page 18, line 405-407 of the revised manuscript). 2. Could the authors comment on why they think that LDE without paclitaxel appears to have 50% as compared with LDE+paclitaxel in mitiigating fibrosis? - As showed in Figure 2, the difference observed in the peritoneal thickness of PF group compared with LDE group was not statistically significant. Thus, we assumed that LDE did not have any effect on peritoneal fibrosis, as expected. 3. Please review this sentence "Conversely, the less expensive, home-based PD procedure, which is more often used in poor countries, has important shortcomings". LMIC (lower and middle income countries) may be a more specific description - Ok, done (Introduction section, page 3, line 67). Reviewer #2: This study investigates the effect of intraperitoneal Paclitaxel on the formation of peritoneal fibrosis following exposure to chlorhexidine gluconate. The topic is important as a sizeable number of patients undergoing Peritoneal dialysis must go over to hemodialysis due to the loss of ultrafiltration ability of peritoneum secondary to fibrosis. The study design is adequate and the experiment appears well performed as the authors covered many relevant aspects. 1. This reviewer would have liked to hear briefly about the potential side effects of Paclitaxel or if the results would have been different if the rats had some sort of kidney impairment. - See comments respecting those issues in the Discussion section (page 19, lines 411-424). We also included 4 papers of our previous studies regarding this issue (see reference list, number 31-34, pages 26-27 of the revised manuscript). Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0268197.r002
25 Apr 2022 Decision Letter - Frank JMF Dor, Editor Use of paclitaxel carried in solid lipid nanoparticles to prevent peritoneal fibrosis in rats PONE-D-21-37828R1 Dear Dr. Maranhão, 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. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Frank JMF Dor, M.D., Ph.D., FEBS, FRCS Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: (No Response) ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: (No Response) ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: No Reviewer #2: (No Response) ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 6. 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: Thank you all questions have been addressed to my satisfaction. I think the clinical relevance of this work remains unclear. Reviewer #2: (No Response) ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No https://doi.org/10.1371/journal.pone.0268197.r003
Formally Accepted
29 Apr 2022 Acceptance Letter - Frank JMF Dor, Editor PONE-D-21-37828R1 Use of paclitaxel carried in solid lipid nanoparticles to prevent peritoneal fibrosis in rats Dear Dr. Maranhão: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Frank JMF Dor Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0268197.r004

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