Obtaining, Evaluation, and Optimization of Doxycycline-Loaded Microparticles Intended for the Local Treatment of Infectious Arthritis

Round 1

Reviewer 1 Report

The topic is interesting but the work should be improved:

 

1. Line 53 - produce or cause?
2. Were all the biopolymers crosslinked with calcium chloride or only alginate?
3. Any cytotoxicity studies? To ensure safe use in biological systems, cytotoxicity should be excluded.
4. Was FTIR performed on wet or dried capsules?
5. The method of antimicrobial analysis is unclear. Were the capsules placed on the agar surface or between the layers? Please add SD values to  inhibition zones diameters.
   
6. FTIR results - the authors describe the origin of the peaks, but do not refer to the differences between the samples.
7. Figure 3 - What is the reason for the difference in the color of the capsules?
8. Figure 4 - please add SD values.
9. To better understand the composition of G1-G8 capsules, I suggest instead of the coded level to present their composition also as a percentage of ingredients.
10. Authors should more emphasize the novelty of their study. For example, there are reports in the literature of alginate capsules loaded with doxycycline.

Author Response

Please see attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

This manuscript describes preparation, characterization and optimization of the microcapsules formulation based on type II collagen, sodium alginate and sodium carboxymethyl cellulose loaded with doxycycline. A model optimization technique by Taguchi method is introduced in detail. It is interesting, but reviewer thinks several points to be considered. Also, several careless mistakes are found.

 

1. In line 167, ‘the compatibility and interactions between polymers and drug were determined’ were described. But, the descriptions on the compatibility and interactions are not found in the text.
2. In Figure 3, reviewer recommend to put a scale bar in each picture.
3. In line 202, the text says ‘each formulation was within a narrow range’. But, there is no support data.
4. In 3.4. Enzymatic degradation, please explain why the reason of the differences on the enzymatic degradation between G1 and G8. Also, reviewer recommends to add the discussion on kinetics of the enzymatic degradation.
5. Table 3 is not introduced in the text.
6. In equation (2), `Total doxycycline amount’ should be substituted with ‘Theoretical doxycycline amount’.
7. The description in line 138 should be deleted.
8. In line 220, 231, 234, and 247, Table 3 is wrong. Table 4 is correct.
9. In line 269, Figure 6a is wrong. Figure 5a is correct.

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Authors have made an effort to improve the paper. I consider that this work can be accepted in its actual form, however please check carefully the missing spaces in some added sentences and in references section.

 

Author Response

Dear Reviwer 1,

Thank you for accepting to review again our paper and accept it with some changes.

We checked carefully the missing spaces and we made the corrections by Track Changes in the attached manuscript.

Best regards,

Authors

Reviewer 2 Report

The authors respond to reviewer's comments carefully. I think this manuscript is acceptable for the publication.

The following part in the text should been revised.

In line 233, "G8 is more stable than G8" is wrong. "G8 is more stable than G1" is correct. Please revise it. 

Author Response

Dear Reviwer 1,

Thank you for accepting to review again our paper and accept it with some changes.

We made the corrections by Track Changes in the attached manuscript.

Best regards,

Authors