Nano-Architectonics of Antibiotic-Loaded Polymer Particles as Vehicles for Active Molecules

Round 1

Reviewer 1 Report

The manuscript entitled “Nano-architectonics of antibiotic loaded polymer particles as vehicles for active molecules” is promising. However major revision is required before publishing to the journal.

In abstract: Line 32-33 is not clear; Recently, nanotechnology researchers have been proved that use of various nanoparticles 32 to target and to annihilate pathogenic microorganisms may be a good solution for drug delivery- It should be rewritten.

Line 35-36; Physicochemical  properties of erythromycin loaded polymer nanoparticles were investigated using particle size 36 distribution, HPLC, FTIR, TG/DTA and SEM techniques. What does it mean by the physicochemical properties? Instead of saying "investigated," it would be a better characterization.

The as prepared samples exhibited an average particle size of 340 and 270 nm respectively, erythromycin assay of 99.7% for both samples (Line 37-38). What does it mean by 99.7% for both samples?

Antibiotic melting peak disappeared for both antibiotic loaded PLA and PLGA nanoparticles 43 thermograph denoting the presence of erythromycin which indicates that the antibiotic is uni- 44 formly dispensed throughout the host matrix at nanometer level. FTIR spectra of Ery-PLA and 45 Ery-PLGA nano-architectures demonstrated chemical structure of drug loaded polymer nanopar- 46 ticles and peaks almost similar (43-47).

These sentences should be rewritten to be more concrete and conclusive.

 

In Introduction:

Bacterial infections happen when microorganisms exhibit its pathogenicity thus 51 inducing disease and causing damage of the host area. Whilst various new drugs were 52 developed to prevent or to treat infections, still remains an important global health 53 problem because of multi-drug resistance and side effects. Although many procedures 54 for prevention and treatment of several infections already exist, there is a vital demand 55 for improved or novel manners for bacterial extermination. A consequence for insuffi- 56 cient therapy could be the inefficient drug delivery although drugs therapeutic efficacy 57 is well established. The occurrence of drug resistance represents a major public health 58 interest resulting from the excess and misuse of the antimicrobial agents by limiting 59 their efficacy. This issue determined multidisciplinary research to find substituted 60 therapies to defeat antibiotic resistance. An important approach to prevent and to treat 61 several infections caused by drug resisting pathogens is the use of nanotechnology in 62 order to deliver antimicrobial agent to the targeted area. These statements are not understandable. Must be re-written.

The advantages of the 63 nano-medicine include the improvement of drug efficiency and stability, decrease of 64 drug toxicity and prolongation of drug release, and precise-targeting to in infected area. Reference must be cited?

Figures 1, 2, and 3 should all be placed in the same place.

The characterization of as synthesized samples was performed in this study to 113 provide useful formulate for a prolonged and controlled drug release system in pre- 114 vention and treatment of several infections. 115 In addition to the obtained nanocomposites used in medicine, medical teams must 116 have key communication skills effective in improving patient care. The authors are unable to differentiate between nanoparticles, samples, and nanocomposites. It must be explained clearly?

It is important to obtain new drug formulation as well as the interdisciplinary 121 communication to reduce morbidity and mortality in health care units. An important 122 aim of this research is to obtain new formulated antibiotic loaded polymer nanostruc- 123 ture with its drug resistance dinamic. Poor spelling and grammatical errors?

Line 129- nano-medicine is important issue for the prevention and treatment of severe infections.  Necessary for authors to state whether or not they are dealing with an infection? Is it a serious illness?

Figure 4 requires a clearer image.

In vitro release study of erythromycin from PLA / PLGA nanoparticles was carried 176 out using Cary 60 UV-Vis – Agilent spectrometer, into a phosphate buffer solution at a 177 pH value of 7.5. This section should be elaborated, and in vitro should be italic.

The percentage content of erythromycin A was calculated using as reference the 207 chromatogram shown in figure 7. (a) and the percentage content of erythromycin B us- 208 ing as reference the chromatogram shown in figure 7. (b). The amount of erythromycin 209 propionate from the nanohybrid samples was expressed as sum of erythromycin A and 210 erythromycin B and it was 99.7% of the initial amount used to prepare the emulsions for 211 both samples. The adequacy of the system was achieved after 5 replicate of reference 212 solution injection resulting a RSD value under 1.0%. It must be explained clearly?

Authors must demonstrate size and charge stability data for at least after 3 months of PLA and PLGA nanoparticle preparation in Figures 5 and 6.

These results presume that bactericidal effect of 311 erythromycin loaded PLA and PLGA nanoparticles is significantly stronger than the 312 antibiotic active substance.

Discussion:

In last few years, local transport of the drug after infected area debridement become 259 for major interest [31,32]. Poly-lactic acid (PLA) and poly (lactic-co-glycolic acid) 260 (PLGA) are biocompatible and biodegradable polymers being a good host for a wide 261 variety of drugs. These sentences should be rewritten to be more concrete.

Antibiotic loaded chitosan nanoparticles obtained by ionic gelation 262 technique using TPP as crosslinking factor are of durable stability. Entrapment of 263 erythromycin active molecules within the network of the polymer matrix implies more 264 stable pharmaceutical formulation. This work concerned on preparing a novel antibiotic 265 carrier using PLA/PLGA nanoparticles loaded with erythromycin using W/O/W double 266 emulsion solvent evaporation method. Erythromycin loaded PLA exhibit 340 nm in size 267 while drug loaded PLGA nanoparticles revealed approximately 270 nm in size. Reference must be cited?

These results presume that bactericidal effect of 311 erythromycin loaded PLA and PLGA nanoparticles is significantly stronger than the 312 antibiotic active substance.

This statement was not proven in this work due to a lack of results. Why are the authors writing this? Checking English grammar and spelling is required in discussion section of the manuscript.

In Conclusion:

We supposed that erythromycin therapeutic efficiency considerably increases 317 by loading the drug into biocompatible polymer based nanoparticles comparing with 318 the free antibiotic. This study reveals that structural and morphological issues of eryth- 319 romycin encapsulated polymer significantly enhanced for antibiotic delivery action. In- 320 fections treatment include destruction of pathogen factor, thus erythromycin loaded 321 polymer assumed to be excellent due to the prolonged release and limitation of side ef- 322 fects. Furthermore, biocompatible and biodegradable polymer showed efficiency for 323 encapsulation of antibiotic molecules acting as a drug carriers used to improve bacterial 324 infections treatment.

These sentences should be rewritten to be more concrete and conclusive.

In line 321-322: Why did the authors write? An erythromycin loaded polymer is thought to be excellent because of its sustained release and few side effects. Have they looked/supporting results at any possible side effects?

Author Response

"Please see the attachament"

Author Response File: Author Response.docx

Reviewer 2 Report

This manuscript refers to the synthesis and the physiochemical characterizations of erythromycin loaded PLA and PLGA nanoparticles, which may provide some guidelines for the design of formulations for a prolonged and controlled release system in prevention and treatment of several infections. However, this manuscript needs some improvements before acceptance for publish. 1. Line 194-205: What is the exact size of PLA and PLGA nanoparticles before and after erythromycin? The descriptions in the results part are not consistent with that in Figure 5 and 6. Please re-check these data. Besides, please provide the distribution pattern of nanoparticles without erythromycin loading. 2. Please provide the PDI data of prepared nanoparticles. 3. This manuscript would be benefited from accurate English language editing.

Author Response

"Please see the attachment"

Author Response File: Author Response.docx

Reviewer 3 Report

Journal: Applied Sciences

Manuscript ID: applsci-1534595

Type of manuscript: Article

Title: Nano-architectonics of antibiotic loaded polymer particles as vehicles

for active molecules

This work describes the synthesis and characterization of erythromycin polymer nanoparticles. The work is well structured, however, there is a lack of novelty, since the loading of erythromycin into polymer nanoparticles has already been reported in the literature. In the same way, the authors did not report the application of the nanoparticles into bacterial strains.

Author Response

"Please see the attachment"

Author Response File: Author Response.docx