Drug Release and Biocompatibility of a Paclitaxel-Coated Balloon Prepared Using the Electrostatic Spray Method
, Qiong Hu 1, Changjiang Pan 3, Dongfang Wang 1, Junfeng Li 1, Chunhai Liu 2, Ming Huang 1, Qian Xiang 1 and Ren Liu 4
Round 1
Reviewer 1 Report
The manuscript coatings-2525950 is a technical study of broad interest for pharmaceuticals and therapeutics knowledgeable. However, I find several shortcomings in its content, which I will try to point out briefly.
I find it inadmissible that the manuscript does not show the structural formula of paclitaxel!
2. The interest of this active ingredient in its antitumor properties cannot be ignored.
3. The interpretation of the FTIR spectra cannot have been made by a qualified researcher. The composition of the sample cannot be deduced from the relative intensity of their bands.
4. I am not surprised that, in general terms, the best results are obtained for the ratio PCX:tartaric acid (H2tart) = 2:1, but why has not been explained. This is undoubtedly due to that PCX has only one N-amide per molecule as protonating site and to the fact that the difference of the pKa values of H2tart (in the order of 3.00 and 4.35) is 1.35 << 4.0. This implies that its two successive dissociations are equivalent, but significantly interacting to each other. In short, the most reasonable, from the acid base point of view, is to expect that each mole of H2tart protonates 2 moles of PCX.
Please carefully revise your manuscript in a printed version.
Author Response
Thank you very much for your comments. We have responded to each item and made revisions in the original text, we’re very appreciative for your efforts to improving this article.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The authors have undertaken a study of the application of an electrostatic spraying approach to the preparation of drug-coated balloon (PCB) catheter material and evaluated the effect of the ratio of an additive to the drug on the properties of the PCB model materials and the drug release characteristics. The manuscript is of potential interest to those working in the subject area of PCBs and others in drug delivery research who would consult the journal Coatings for new research findings. Some improvement to the manuscript should be undertaken before it is considered further for possible publication.
The following specific points need to be addressed:
Page 1 line 42 states "Drug coated balloon (DCB) was e a new means of treating....". Add hyphen between "drug" and coated" and delete the "e" after "was". Check the entire manuscript to ensure the hyphen between "drug" and coated" is employed consistently where appropriate.
Page 2 line 48: add full stop/period between "release" and "Typically".
Page 2 line 67: Indicate supplier of Nylon 12 used and what were the dimensions of the material used in the study.
Page 2 line 71: what grade of PVP was used and indicate the supplier. Was the mass of PVP retained on the Nylon 12 surface measured. Is it critical to the paclitaxel coating addition? If so how was the amount e.g., microgram/ mm2 controlled?
Page 2 lines 73-77: please give more details of the coating equipment, indicate individual components and where they were sourced from. Ideally, if the equipment has been described elsewhere in published research work please add a reference. Consider adding a diagram of the equipment arrangement used.
Page 2, table 1: it is noted that acetonitrile is used as the major component of the solvent for the coating solution. As a class 2 solvent in respect of residues in finished pharmaceutical product its levels in those products must be well controlled. Please consider including a comment on this in describing the drying process for the coated polymer.
Page 2 lines 84-87: how does the water solubility and hence dissolution of the tartaric acid affect the measurement of contact angle? You do not indicate if the test was done to control the dissolution of the acid during the the test.
Page 3 lines 5 -94: what were the dimensions of the PCB samples tested for drug release and hence what is the amount of paclitaxel investigated in the drug release test? Please add these details. How does this amount relate to the solubility of paclitaxel in the drug release test medium, PBS? Is the test operating under sink conditions? What are the implications if it is not sink condition?
Page 3-4 section 2.4: throughout each subsection in this section the amount of DCB employed is not indicated clearly. This detail must be added, as it is unclear exactly how the performance of the experimental DCBs in these biocompatibility evaluations was undertaken.
Page 5 Fig 1: include spectrum of tartaric acid. Quality of spectra is not good, and picking out the peaks contributed by paclitaxel from peaks contributed by tartaric acid will be difficult with current spectra. Hence hard to draw conclusions made in section 3.1.
Page 5 lines 163-173: how did you identify that the needle crystals were paclitaxel and not tartaric acid ?
Page 7 section 3.3: how does the behaviour of the drug release of these samples compare with existing commercial paclitaxel DCBs/ Or with samples prepared by the deposition method used without the tartaric acid?
Page 13 section 4: is it worth adding more discussion about the benefit of electrostatic spraying to make DCBs?
Author Response
Thank you very much for your comments. We have responded to each item and made revisions in the original text, we’re very appreciative for your efforts to improving this article.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
Improved enough to recommend acceptance. I appreciate the efforts of the authors.
Author Response
Thank you very much for your dedication to this article, which is very important for improving the quality of the paper. Thank you again.
Reviewer 2 Report
The authors have considered reviewer feedback and made improvements to the manuscript. Overall the responses to my concerns are good. However, there are still areas in the manuscript where there previously noted significant concerns were raised and where a better response is requested to make the manuscript more suited for further consideration for publication.
Page 2 line 71: authors have provided some more useful detail of the PVP coating process. However, my comment as given is not properly addressed as to the reliability of the application of the PVP coating. Specifically, the mass of PVP retained on the Nylon 12 surface has not been measured and shown to be reproducible. The criticality of a good surface coverage to the paclitaxel deposition may be such that some further indication that this is being controlled should be given. After dipping pre-weighed nylon 12 and allowing solvent to evaporate, please reweigh and calculate amount of PVP applied in mg or micrograms/cm2. Run three replicates to confirm process is reproducible.
Page 2 lines 84-87: the authors' response to the prior question on tartaric acid does not really answer my question. Due to the water solubility and of the tartaric acid it will dissolve in the water used to carry out the contact angle measurement and so affect the measurement of contact angle - it may change during making the measurement, or replicates may show poor reproducibility. You do not indicate if the test was done in a way to control the dissolution of the acid during the test and so assure reliability and integrity of the data provided.
Author Response
Thank you very much for your dedication to this article, which is very important for improving the quality of the paper. We have carefully revised the entire text.
Author Response File: Author Response.pdf
