Nanoscale Self-Assemblies from Amphiphilic Block Copolymers as Proficient Templates in Drug Delivery

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

 

The Authors of the manuscript titled “Nanoscale self-assemblies from amphiphilic block copolymers as proficient templates in drug delivery” made a brief introduction to block copolymers including structural design, synthesis, types of block copolymers, and behaviour of block copolymers in aqueous solution.

 

1. Despite that I am not qualified in a hundred percent to assess the quality of English in this paper, the manuscript has many typos and grammar errors, and some paragraphs may be rewritten to be more understandable (for example, in introduction section, page 3, lines 3-7: “Unlike polyblends which are recycled modified plastics, nanocomposites and interpenetrating polymer networks which are physical mixtures of two incompatible polymers that undergo phase separation at macroscopic scale, BCPs undergo only a microheterogeneous separation due to covalent bonding that connects different blocks”). Therefore, it needs moderate editing English language. Additionally, the Authors several times use “etc” at the end of a sentence, I suggest that they may type down “etcetera” or use synonyms.

2.  What do the Authors mean by “certain instruct” in the following sentence? “Fig. 1 illustrate different structures of such smart BCPs consisting of at least two or more polymeric blocks often incompatible arranged in a certain instruct such as linear, cyclic or star-like fashion, etc.” Does mean conformation, architecture?

3. In section “Types of BCPs, Double hydrophilic block copolymers (DHBCs)”, the list of polymers given in the follow sentence “(i) Natural based are, for example, like hydroxypropyl cellulose, chitosan, alginate, sulfated polyscaccharides and (ii) Synthetic neutral polymers like poly(ethylene oxide), polyvinylpyrrolidone, polyvinylalcohol, poly(N-isopropylacrylamide), polyvinylcaprolactam and various polyelectrolytes (anionic, cationic or zwitterionic) such as polyacrylates, poly(vinylpyridinium chloride), poly(diallyldimethylammonium chloride), poly(styrene sulfonate), etc.“ cannot classified as blockcopolymers. Then, Figures 3 and 4 do not correspond to the text. The Authors should re-write this section based on the documents 33-36. It is important to note that “schizophrenic” refers to one of the blocks of the copolymer being incompatible with water or a given solvent.

4. The “magnetic-responsiveness” is not a copolymer. It is a composite material.

5. In “Self-assembly in BCPs” I hoped to read about the physicochemical process of the assembly in blockcopolymers. The text of this section is suitable for introducing the following sections, then, I suggest change the title.

6. Should the Authors provide information about the structural requirements for a given blockcopolymer being formed micelles or polymerosomes?

7. This is a review of blockcopolymers, then, why do the authors include random copolymers examples? Section: Polyion complex micelles (PICMs) “Using random copolymers with pendant quaternary ammonium and sulfonate groups, Shukanta et al. created PICMs using RAFT technique to create anionic random copolymers from MPC and potassium 3-(methacryloyloxy) propane sulfonate and cationic random copolymers from 2-(methacryloyloxy)ethyl phosphorylcholine with methacroylcholine chloride.”

Author Response

Response to reviewers

 

Manuscript ID: ddc-2682750

Manuscript title: “Nanoscale self-assemblies from amphiphilic block copolymers as proficient templates in drug delivery”

 

Reviewer 1:

The Authors of the manuscript titled “Nanoscale self-assemblies from amphiphilic block copolymers as proficient templates in drug delivery” made a brief introduction to block copolymers including structural design, synthesis, types of block copolymers, and behaviour of block copolymers in aqueous solution.

1. Despite that I am not qualified in a hundred percent to assess the quality of English in this paper, the manuscript has many typos and grammar errors, and some paragraphs may be rewritten to be more understandable (for example, in introduction section, page 3, lines 3-7: “Unlike polyblends which are recycled modified plastics, nanocomposites and interpenetrating polymer networks which are physical mixtures of two incompatible polymers that undergo phase separation at macroscopic scale, BCPs undergo only a microheterogeneous separation due to covalent bonding that connects different blocks”). Therefore, it needs moderate editing English language. Additionally, the Authors several times use “etc” at the end of a sentence, I suggest that they may type down “etcetera” or use synonyms.

Author’s response:

We have modified and changed the language of these sentences and highlighted them in yellow. Also, we have replaced the word etc. to etcetera.

 

2. What do the Authors mean by “certain instruct” in the following sentence? “Fig. 1 illustrate different structures of such smart BCPs consisting of at least two or more polymeric blocks often incompatible arranged in a certain instruct such as linear, cyclic or star-like fashion, etc.” Does mean conformation, architecture?

Author’s response:

Here “certain instruct” means architecture. We have changed this word for better clarity to readers.

 

3. In section “Types of BCPs, Double hydrophilic block copolymers (DHBCs)”, the list of polymers given in the follow sentence “(i) Natural based are, for example, like hydroxypropyl cellulose, chitosan, alginate, sulfated polyscaccharides and (ii) Synthetic neutral polymers like poly(ethylene oxide), polyvinylpyrrolidone, polyvinylalcohol, poly(N-isopropylacrylamide), polyvinylcaprolactam and various polyelectrolytes (anionic, cationic or zwitterionic) such as polyacrylates, poly(vinylpyridinium chloride), poly(diallyldimethylammonium chloride), poly(styrene sulfonate), etc.“ cannot classified as block copolymers.

Author’s response:

Thank you very much for pointing out this important mistake. Surely, the examples mentioned are homopolymers. Hence we have changed the caption of Figure 2.

Then, Figures 3 and 4 do not correspond to the text. The Authors should re-write this section based on the documents 33-36. It is important to note that “schizophrenic” refers to one of the blocks of the copolymer being incompatible with water or a given solvent.

Author’s response:

We have now modified this section based on the documents 33-36.

 

4. The “magnetic-responsiveness” is not a copolymer. It is a composite material.

Author’s response:

You are correct that "magnetic-responsiveness" is not a copolymer, but it is a property of a composite material. Specifically, magnetic-responsive materials are typically composites that contain magnetic particles dispersed within a polymer matrix. We have now mentioned this modification [37-43].

 

5. In “Self-assembly in BCPs” I hoped to read about the physicochemical process of the assembly in block copolymers. The text of this section is suitable for introducing the following sections, then, I suggest change the title.

Author’s response:

As per reviewer’s suggestion, we have now changed the title.

 

6. Should the authors provide information about the structural requirements for a given blockcopolymer being formed micelles or polymersomes?

Author’s response:

Now we have provided appropriate information with relevant references.

 

7. This is a review of block copolymers, then, why do the authors include random copolymers examples? Section: Polyion complex micelles (PICMs) “Using random copolymers with pendant quaternary ammonium and sulfonate groups, Shukanta et al. created PICMs using RAFT technique to create anionic random copolymers from MPC and potassium 3-(methacryloyloxy) propane sulfonate and cationic random copolymers from 2-(methacryloyloxy)ethyl phosphorylcholine with methacroylcholine chloride.”

Author’s response:

The brief inclusion of random copolymers with a few examples mentioned is done with an intention to provide a broader context to the readers about the self-assembly behavior that the amphiphilic BCPs undergo and exhibit varied micellar architectures that possess their versatility in drug delivery applications.

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript of Patel D. and co-workers provides a literature review on amphiphilic block copolymers as proficient templates in drug delivery. The authors focused their study on the current enlargements in the formation and properties of various nanostructured aggregates resulting from the self-assembly of a variety of block copolymers in an aqueous solution. The manuscript gives an in-depth picture of the nanoscale micellar aggregates formed from amphiphilic block copolymers (BCPs), stimuli-responsive double hydrophilic block copolymers (DHBCs), and polyion complex micelles (PICMs) including preparation methods, properties, and application examples. The manuscript is logically divided into very accurate and fully comprehensive sections. The technical quality of this work is very good. An in-depth literature analysis regarding amphiphilic block copolymers demonstrates their potential for technological and biomedical applications.

In my opinion, this contribution provides an updated and valuable perspective on the important topic and will bring a range of readers. Generally speaking, this is a nice piece of work and should be published without any doubts.

Author Response

Authors are highly thankful to receive very positive comments from reviewer.  

Reviewer 3 Report

Comments and Suggestions for Authors

Dear Editor, in this review authors have presented the applications of nanoscale self-assemblies using amphiphilic block copolymers in drug delivery. The review is well organized and provides in a good way all published informations. It can be published as it is. However, I propose to increase the quality of included figures.

Comments on the Quality of English Language

Dear Editor, in this review authors have presented the applications of nanoscale self-assemblies using amphiphilic block copolymers in drug delivery. The review is well organized and provides in a good way all published informations. It can be published as it is. However, I propose to increase the quality of included figures.

Author Response

Authors are thankful to reviewer for evaluating and scrutinizing the review and give their positive feedbacks towards the publication. However, Reviewer suggested to increase the quality of Figures. In response to that, we have included these changes and improved the figure quality.

Reviewer 4 Report

Comments and Suggestions for Authors

The manuscript by Patel et al. is an overview of amphiphilic block copolymers self-assembling into nanoscale delivery systems. The manuscript is well illustrated and organized, but the content appears poor and episodic. Better systematization and analysis are needed. The manuscript suffers from numerous shortcomings.

1.      From the text of the review, it is not clear how this content is agreed with the paper topic and journal title.

2.      Figure 1, the last row describes graft-copolymers but not block-copolymers.

3.      Section devoted to DHBCs and Figure 2. An important class of hydrophilic polymers is omitted, namely poly(amino acids) (or polypeptides), e.g. poly(L-glutamic acid), poly(L-aspartic acid), poly-L-lysine, poly-L-histidine, etc.

4.      The examples of hydrophobic polymers should also be summarized.

5.      Figures 6 and 7. The names of polymers are written incorrectly. The names of monomers consisted of two words, should be taken in brackets. For example, poly(ethylene glycol) instead of polyethylene glycol. Instead of poly (methyl vinyl) ether, it should be poly(methyl vinyl ether). No space should be added between “poly” and “monomer name”.

6.      The names of polymers should be carefully checked throughout the text and corrected.

7.      Poly(glutamic acid), poly(aspartic acid) and polyhistidine are also pH-responsive and are widely used for pH-sensitive drug release. These polymers should be indicated also in Figure 7.

8.      Section “Polymeric micelles”. Amphiphilic copolymers may self-assemble not only into spherical but also into rod-like (worm-like) micelles. It should be also discussed in the text.

9.      Besides micelles and polymersomes, amphiphilic block-copolymers can self-assemble into vesicles. It is applicable for amphiphilic tri-block copolymers. This type of self-assembled structures should be discussed.

10.  The criteria of self-assembly of block-copolymers into specific structures should be analyzed.

11.  How do polyionic micelles and two-hydrophilic blocks relate to self-assembly from the amphiphilic block copolymers claimed in the title?

Author Response

1. From the text of the review, it is not clear how this content is agreed with the paper topic and journal title.

Author’s response:

We have added relevant justifying text in the Introduction section. 

 

2. Figure 1, the last row describes graft-copolymers but not block-copolymers.

Author’s response:

Thank you very much for your fruitful suggestion. We have modified the figure.

 

3. Section devoted to DHBCs and Figure 2. An important class of hydrophilic polymers is omitted, namely poly(amino acids) (or polypeptides), e.g. poly(L-glutamic acid), poly(L-aspartic acid), poly-L-lysine, poly-L-histidine, etc.

Author’s response:

We have now made the necessary changes in the revised draft.

 

4. The examples of hydrophobic polymers should also be summarized.

Author’s response:

We have added the relevant text of the hydrophobic polymers along with the examples in text.

 

5. Figures 6 and 7. The names of polymers are written incorrectly. The names of monomers consisted of two words, should be taken in brackets. For example, poly(ethylene glycol) instead of polyethylene glycol. Instead of poly (methyl vinyl) ether, it should be poly(methyl vinyl ether). No space should be added between “poly” and “monomer name”.

Author’s response:

We have made corrections in Figure 6 and 7 as suggested.

 

6. The names of polymers should be carefully checked throughout the text and corrected.

Author’s response:

We have made corrections throughout the text carefully.

 

7. Poly(glutamic acid), poly(aspartic acid) and polyhistidine are also pH-responsive and are widely used for pH-sensitive drug release. These polymers should be indicated also in Figure 7.

Author’s response:

We have included relevant examples in Fig 7.

 

8. Section “Polymeric micelles”. Amphiphilic copolymers may self-assemble not only into spherical but also into rod-like (worm-like) micelles. It should be also discussed in the text.

Author’s response:

Now we have provided appropriate information with relevant references.

 

9. Besides micelles and polymersomes, amphiphilic block-copolymers can self-assemble into vesicles. It is applicable for amphiphilic tri-block copolymers. This type of self-assembled structures should be discussed.

Author’s response:

Amphiphilic block-copolymers can self-assemble into vesicles or polymersomes. Here both terms are same and can be use alternatively. When the structure is made from surfactants its known as vesicle and when it makes from amphiphilic block-copolymer, it is known as Polymersomes. However, many authors use both the term necessarily.  

 

10. The criteria of self-assembly of block-copolymers into specific structures should be analyzed.

Author’s response:

Now we have provided appropriate information with relevant references.

 

11. How do polyionic micelles and two-hydrophilic blocks relate to self-assembly from the amphiphilic block copolymers claimed in the title?

Author’s response:

We have highlighted the text.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript lacks a bioethical statement (declaration), which is necesary for in vivo studies.

Author Response

Reviewer 1:

The manuscript lacks a bioethical statement (declaration), which is necessary for in vivo studies.

Author Response: We have already included declaration statement as below:

THE ETHICS STATEMENT: No human or animal subjects were used in this research.

 

However, in this review article, in-vivo or in-vitro studies described is a summary of other published articles. We did not perform any kind of biological studies.

Reviewer 4 Report

Comments and Suggestions for Authors

The authors have added the recommended information, but without proper citation. Wherever new information has been added, appropriate literature citations should be provided. 

Author Response

Reviewer 2:

The authors have added the recommended information, but without proper citation. Wherever new information has been added, appropriate literature citations should be provided.

Author Response: We have added and highlighted references related to new added text.