Potential of Deer Placenta Extract in Hair Cell Regeneration and Its Nanoniosome-Microspicule Gel as a Transfollicular Delivery System

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Authors have developed deer placenta extract into nanoniosome and Microspicule Gel platforms for delivery. The formulation data is fine; nonetheless, significant problems must be addressed to guarantee the proper delivery of the active components. My comments are as follows:

1)      Authors are unaware that chemotherapy-induced hair loss is not caused by cisplatin. The selected drug is inappropriate. Kindly use the appropriate anticancer drug. Please repeat this simple experiment.

2)      It is recommended to utilise ImageJ to quantify the closing gap for Figure 2. This will yield a more quantitative test than qualitative.

3)      What methodology did you employ to ascertain the 0.2% w/v concentration of DPE and the 1% w/w concentration of MS for the formulation? No optimisation study has been conducted.

4)      Figure 6. The photos require labelling for the skin layer and specifically identifying the hair follicles. It is inadequate to only include words; the photos must also be captioned.

5)      Figure S1 is missing from the file.

6)      To deliver to the hair follicles, it is necessary to penetrate the epidermis, which exceeds 160 µm in depth. Kindly see figure 1 of this paper for a visualisation of the skin layer's depth: https://pubs.acs.org/doi/10.1021/jacsau.2c00432. Your formulation can only penetrate to 60 µm, which is inadequate for reaching the dermis, where hair follicles are predominantly situated. Your formulation has just penetrated the epidermis. This indicates a necessity to enhance the formulation.

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The subject of the reviewed article is very interesting. The studies contained in it indicate a possible way to solve the problem of treating alopecia caused by drugs (e.g. drugs used in the treatment of cancer) or other factors. The use of active ingredients contained in the deer placenta extract (DPE) for this purpose is interesting.

 

The article is very valuable and contains interesting studies, but reading it leaves one feeling a certain dissatisfaction. In my opinion, it lacks a description of the following issues:

1) The Materials and Methods section describes the method of obtaining drug delivery systems (DDS) in the form of NS and NS-MS. In my opinion, a color diagram showing the stages of creation of these systems should also be presented here. This would then be clearer for the reader of the manuscript.

2) In what forms of epidermal drugs could the DDS described by the authors in the form of NS and NS-MS be used? In what cosmetic formulations can they be used?

3) Could the extract obtained also be used in the treatment of acne?

4) Would such extracts be effective in placentas of other animals as well? Why were deer placentae selected for the study? What is the availability of such placentae?

5) The synergistic mechanism for NS-MS described on page 10 should be presented in the form of a diagram.

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

This article explores the potential of Deer Placenta Extract (DPE) in hair follicle cell regeneration and proposes a hair follicle-targeted delivery system by loading DPE into a nanovesicle-microneedle (NS-MS) gel. The study examines the regenerative effects of DPE on hair follicle cells, especially those damaged by chemotherapy, and develops an NS-MS-based system to enhance DPE's skin permeation and follicle penetration. The results show that DPE significantly enhances cell proliferation and migration at an optimal concentration, aiding cell recovery both before and after chemotherapy.

 

I have some suggestions for modifications:

The layout of Figures 2 and 5 is quite poor, and it should be determined whether Figure 5 requires significance markers, and whether the scale bars in Figures 2 and 6 are clear.

Issues with Data Accuracy and Consistency: The study used a relatively high concentration of Deer Placenta Extract (2000 µg/mL) without specifying the effects at lower concentrations. Furthermore, the differences in effects at various concentrations and the experimental design were not thoroughly analyzed in the discussion, and there may be a tendency to selectively present favorable data. For instance, the penetration depth of the NS-MS system is described as significantly superior to the system without a carrier, but no complete numerical comparison or statistical analysis was provided to support this conclusion.

Additional Pathways in Discussion: In line 310, several pathways could be added:PI3K/AKT, Wnt, and EGF have been shown to promote cell cycle progression in the dermal papilla cells of hair follicles and enhance cell proliferation (Ying Gao, 2024, FASEB; Jimin Han, 2022, Front Cell Dev Biol).FGF-2 and IGF-1 play crucial roles in inducing or maintaining the growth phase of cells, supporting the hair growth cycle, and preventing apoptosis during the telogen phase.Additionally, members of the TGF-β and Wnt families are essential for follicle development and cycling, as they promote follicle cell proliferation and hair growth (Jimin Han, 2022, Front Cell Dev Biol).

Comments on the Quality of English Language

The English could be improved to more clearly express the research.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Authors have addressed my comments.

Reviewer 3 Report

Comments and Suggestions for Authors

I think it's a good change, and it's ready for publication now.