Effect of Aqueous Extracts of Quercus resinosa on the Mechanical Behavior of Bigels

Round 1

Reviewer 1 Report

The authors have reported on the mechanical behaviour of bigels loaded with aqueous extracts of Quercus resinoa. The manuscript maybe considered for publication after attention to the following:

1. Introduction - please describe why the study of rheological behaviour of active compound loaded bigels are important?

2. Describe how the aqueous extracts were loaded in the bigels? What were the control samples? 

3. Conclusion - significant portion of the manuscript is on the microbial studies of the active compounds, however this is not discussed in the conclusion. Please include this in the conclusion.

line 15 - please correct spelling "oloeogels" to "oleogels"

line 137 - correct "1x10⁴ CFU"

line 146 - correct spelling "bigeles" to "bigels"

Author Response

Thank you very much for comments from reviewers

The authors have reported on the mechanical behaviour of bigels loaded with aqueous extracts of Quercus resinoa. The manuscript maybe considered for publication after attention to the following:

1. Introduction - please describe why the study of rheological behaviour of active compound loaded bigels are important?

R= New paragraph was introduced into the revised version

“]. In this sense, the development of soft dosage forms as vehicle to transport bioactives for topical use is important in pharmaceutical industry. They are dispersed systems with a distinctive viscoelastic behavior. Their viscous behavior at a given temperature and shear stress is non-linear, depending on the shear rate [12]. This complicates the mechanical analysis because during the developing of soft dosage vehicles (i.e., as bigels), the study of their mechanical properties is useful to determine their stability [13]. Also, it is a useful tool to obtain objective criteria for quality control, production, storage, release of bioactives, and consumer requirements [14]. Several models have been used as the Creep cycles [15], the Palierne model [16], the Krieger-Dougherty model [17] and the semi-empirical model proposed by Lupi et al. [13]. The complexity of the rheological behavior remains unknown. A relatively simple alternative to study rheological behavior is the Carreau-Yasuda model [18].”

2. Describe how the aqueous extracts were loaded in the bigels? What were the control samples?

It was described as:

“Quercus leaves extract load into the Bigels

Once the oak infusions were obtained [25], they were frozen and lyophilized. Subsequently, in the aqueous phase (hydrogel), different concentrations of the aqueous infusions (i.e., 500, 1000, 2000, 3000 and 4000 mg/mL of sample) were resuspended in the aqueous phase of hydrogel, until their complete dissolution. In the case of the rheological analyses, the control samples were the bigels without load. The higher concentrations 3000 and 4000 mg/mL were tried but presented solubility problems.”

3. Conclusion - significant portion of the manuscript is on the microbial studies of the active compounds, however this is not discussed in the conclusion. Please include this in the conclusion.

The conclusion was re-wrote as follows:

“The flavonoid profile in special flavonols, found in aqueous extracts from Quercus shows strong inhibition against Cutibacterium acnes and Staphyloccocus epidermidis. The inhibition was concentration dependent, however, the highest concentration of extracts exhibited solubility problems. The behavior of the liquid portion of the bigels fits the Power law model very well, finding a pseudoplastic type behavior (n < 1), in all samples, the bigels loaded with aqueous extracts of oak leaf showed a consistency index greater than that of the unloaded samples. Regarding the viscoelastic behavior, the analysis was carried out by approximating the Carreau-Yasuda model to the viscoelastic behavior, observing that the presence at low concentrations of phenolic compounds in the bigels, improves their mechanical properties, increasing the viscosity. complex, without affecting interfacial interactions, except at very high concentrations of polyphenolic compounds, the Carreau-Yasuda model was successful in evaluating the viscoelastic behavior of bigels.”

line 15 - please correct spelling "oloeogels" to "oleogels"

R= It was done

line 137 - correct "1x104 CFU"

R= It was done

line 146 - correct spelling "bigeles" to "bigels"

R= It was done

Reviewer 2 Report

This study aims to evaluate the effect of phenolic compounds present in oak leaf extracts on the rheological properties of bigels. Despite the interesting topic of the study, the method of presenting the results needs to be improved. Therefore, the manuscript can be accepted for publication if the following points are addressed:

1.     what is the novelty of your study? you should highlight on it in introduction.

2.     In line 205, is it a heading or a paragraph?

3.     2.   In Figure 1, needs an arrangement of the images and relocation after the description as well as an addition of scale bars.

4.     In line 223-224, the following paragraph appears: The images show few differences between the unloaded and loaded bigels at the lowest extract concentration (500°g/mL). Please review the unit.

5.     concentration units must be reviewed. For example, in line 282, the unit of concentration is from 1000 to 3000 g / ml. They are irrational values.

6.     What is the nature of the interactions between the hydrogel and an organogel, and between bigel and the extract? FTIR analysis must be done to confirm this.

7.     I suggest carrying out cyclic creep recovery test to study long-term viscosity effects at several stress levels.

8.     Was the antibacterial property of the bigel tested after incorporation of the extract in it?

9.     Figure 2 that cited on line 339 is not in the manuscript.

10.  What worries me is the problems with the English language that in places impede understanding of the text. Thus, a thorough review of the language by an expert is required.

Author Response

Answer to reviewer 2

Thank you very much for comments from reviewer

This study aims to evaluate the effect of phenolic compounds present in oak leaf extracts on the rheological properties of bigels. Despite the interesting topic of the study, the method of presenting the results needs to be improved. Therefore, the manuscript can be accepted for publication if the following points are addressed:

1. what is the novelty of your study? you should highlight on it in introduction.

The introduction was re-wrote as follows:

“Several reports have described the effect of phenolic compounds on hydrogel mechanical stability [11]. In this sense, the development of soft dosage forms as vehicle to transport bioactives for topical use is important in pharmaceutical industry. They are dispersed systems with a distinctive viscoelastic behavior. Their viscous behavior at a given temperature and shear stress is non-linear, depending on the shear rate [12]. This complicates the mechanical analysis because during the developing of soft dosage vehicles (i.e., as bigels), the study of their mechanical properties is useful to determine their stability [13]. Also, it is a useful tool to obtain objective criteria for quality control, production, storage, release of bioactives, and consumer requirements [14]. Several models have been used as the Creep cycles [15], the Palierne model [16], the Krieger-Dougherty model [17] and the semi-empirical model proposed by Lupi et al. [13]. The complexity of the rheological behavior remains unknown.

 A relatively simple alternative to study rheological behavior is the Carreau-Yasuda model [18]. Some authors [19;20] have used a Carreau-Yasuda model to evaluate the rheological behavior of bigels loaded with vitamin E and organogels loaded with vitamin E, respectively. They found that the use of the Carreau-Yasuda model and their parameters could help to identify changes in the mechanical properties of bigels and organogels. Generally, viscoelastic properties of materials obtained by rheological methods could deliver data about several properties as structure, phase behavior, and physical interactions [21;22]. The most known model for complex viscosity is the Carreau-Yasuda, which correlates complex viscosity to zero complex viscosity, relaxation time, power law index and width of the transition between Newtonian and Power law behavior [23]. The expression is shown next:

                                         (1)

Where,

h*(w) is complex viscosity

h0* is zero complex viscosity

l is the relaxation time

n is the Power law index

i* is the shear stress at the transition zone

a indicates width of the transition between Newtonian to Power law behavior

And the relaxation time can be defined as:

                                                                                                                    (2)

Usually, equation 1 has been used by researchers in several areas of knowledge, focusing on fitting the model to experimental data and determine the parameters. However, more recently several groups have used this model to obtain more information about material properties [21]. Thus, the objective of this work is to evaluate the effect of the presence of phenolic compounds from oak leaf extracts on the rheological properties of bigels.”

2. In line 205, is it a heading or a paragraph?

R=Thank very much for your observation, This error, was corrected

3. In Figure 1, needs an arrangement of the images and relocation after the description as well as an addition of scale bars.

R= It was corrected as follows:

Figure 1.A unloaded bigel; B Bigel loaded (500 mg/mL extract of Q. resinosa); C Bigel loaded (1000 mg/mL extract of Q. resinosa); D Bigel loaded (2000 mg/mL extract of Q. resinosa). 100x, scale bar size 200 mm.

4. In line 223-224, the following paragraph appears: The images show few differences between the unloaded and loaded bigels at the lowest extract concentration (500°g/mL). Please review the unit.

Thank very much for the observation, it was corrected

5. concentration units must be reviewed. For example, in line 282, the unit of concentration is from 1000 to 3000 g / ml. They are irrational values.

Thank you very much for the observation, all units along the manuscript were revised and corrected

6. What is the nature of the interactions between the hydrogel and an organogel, and between bigel and the extract? FTIR analysis must be done to confirm this.

Unfortunately we dont make FTIR or Raman measurements in the present experiment, however, data published by Fasolin et al., (2021) indicates that interaction between hydrogel and oleogel in bigels are of physical nature.

Your observation is clear, nowadays, more deep studies about the nature of these interactions are conducted by FTIR, Raman microscopy and ITC, however, in the present contribution our objective was to evaluate the effect of extracts of Quercus and the mechanical behavior of bigels

7. I suggest carrying out cyclic creep recovery test to study long-term viscosity effects at several stress levels.

Your observation is very useful, However, these experiments are proposed to make in a near future, because the use of the rheometer is complicated in our institution

8. Was the antibacterial property of the bigel tested after incorporation of the extract in it?

The reviewer observation is correct, in the present experiment, only was probed the dose of extract in order to load the bigel, however, was not probed the loaded bigel against microorganisms.

9. Figure 2 that cited on line 339 is not in the manuscript.

Thank you very much for your observation, the figure was introduced into the text:

Figure 2. Rheological behavior of complex moduli of the unloaded and loaded bigels with aqueous extract of Quercus leaves.

10. What worries me is the problems with the English language that in places impede understanding of the text. Thus, a thorough review of the language by an expert is required.

All revised  version of the manuscript was revised for a Certified English Teacher from  Language center of our Institute.

Round 2

Reviewer 1 Report

The authors have attended to the reviewers comments in an appropriate and acceptable manner. The corrections have been done as suggested and the manuscript is now in a better shape. The manuscript can now be accepted for publication, with attention given to minor English language corrections.

Reviewer 2 Report

Authors response to most of the suggested points.So, I recommend to that the manuscript be accepted for publication.