Evaluation of Drug Release Profiles of Titanium Plates Coated with PLGA or Chitosan with Meropenem Using UPLC: An In Vitro Study

Round 1

Reviewer 1 Report

This study evaluates the drug release of titanium plates in vitro

Coated with PLGA or Chitosan with Meropenem using UPLC.

In particular, it has been observed, with a simple but original protocol, that the coating of titanium plates with PLGA or chitosan with Meropenem appears to improve the delivery of a therapeutic agent to prevent or treat a bacterial infection.

The length of this manuscript is sufficient and the writing is clear. The introduction is very concise and you should also integrate it with more up-to-date bibliography.

Materials and methods are well described and are reproducible.

The results are clear, but very synthetic. The captions of the tables and figures are insufficient to adequately describe the results of the experiments.

The discussion is clear and adequate. and discussion:

The conclusion is synthetic.

The bibliography should be integrated with more recent articles.

Author Response

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Reviewer 2 Report

The authors investigate polymer coated titanium plates for efficient and sustainable release of antimicrobial drug. Results are presented for PLGA and chitosan coatings and for non-coated titanium plates, considering possible effects of sterilization.

The following minor revisions are suggested before publication of the manuscript:

1) Regarding the quantities of released drug in days 1, 3, and 7, it would be much better to also mention the corresponding fractional release (i.e. the drug quantities mentioned in the Tables, in what percentages of the initial drug loading correspond?). This will be also useful for the readers in order to have and idea for how long the release can be sustained in the examined cases. No need to point out that commonly in the literature the release profiles present the fractional drug release for different times.

2) What is shown in the three last columns of Table I ?  They are nowhere discussed in the paper. It should be explained what is their meaning, otherwise they should be removed. 

3) The p-values mentioned on Table I carry no information, as they compare release data in different days. They should be removed.

4) The phrase in line 212 "On day 1, all three materials (M, MP, MC) showed similar release" is incompatible with that mentioned  two sentences below (lines 214, 215) regarding delayed drug release due to the polymer carriers.

5) Actually the polymer coatings show more rapid and not delayed drug release on days 3 and 7 as compared to the non-coated case. Therefore the phrases about delayed or "retard" (line 220) release should be revised. This result seems to be counterintuitive and should be further discussed. Are there similar results in the literature?

6) If the drug is covalently linked to the polymer (see e.g. https://doi.org/10.3390/ijms222010960 ), or there is an additional external layer with no drug (se e.g. https://doi.org/10.3390/pr10122592 ), would this result in more sustained release?

7) Line 224: "it showed delayed drug release on day 3 and 7 compared to day 1". How is derived this conclusion from the data? It should be clarified. 

8) The whole text from line 258 up to line 279 should be moved to the Introduction, as it is not discussed any particular result of the current study, but instead general things are mentioned.

9) There is a typo in line 42/43 in the first page.

Author Response

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Reviewer 3 Report

This in-vitro study is to investigate the effect of drug release from the titanium plate which have been coated with PLGA/Chitosan with antimicrobial agent Meropenem. The study design is appropriate, but required some modifications of the manuscript for clarity of the presentation.

1.       Abstract – use full term for the abbreviation. Abstract is the first capture of the attention of the readers. Changed the word ‘seven’ to ‘7’.

2.       Introduction

Line 42 - What are the various reasons of the complaints? Need elaboration.

Line 42 – formatting error ‘2 Materials and Methods’?

3.       Material and Methods

Line 88 – formatting error

Line 95 – name the grouping for these 3 solutions: MP, MC, M

Line 98 – How to measure these 2 parameters (5mg MEM and 25 mg polymer) by weight?

Line 100 - How does the 54 samples divided into the 3 types of solutions?

Line 123 – It is unclear why non-sterile group is included. Need some background information. What is the clinical implication? How does the non-sterile gp being prepared? The term non-sterile is misleading. Suggest to change the name: eg 'non-irradiated group'?

4.       Discussion

Line 225 - What is the clinical implications of the ‘7d time frame’? The contamination of the plates usually happened after years of placing. How to apply the 7d time frame into this context?

There are few formatting errors that required amendment

Author Response

the reply is attached 

Author Response File: Author Response.docx