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Development of Chitosan-Based Nanoemulsion Gel Containing Microbial Secondary Metabolite with Effective Antifungal Activity: In vitro and in vivo Characterizations
PURPOSE: Microbial resistance to antibiotics is one of the most important public health concerns of the 21(st) century. We isolated, purified, and structurally elucidated antifungal secondary metabolites from red soil microbes and encapsulated them into chitosan (CS)-based nanoemulsion (NE) gel (NEG...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8689013/ https://www.ncbi.nlm.nih.gov/pubmed/34949923 http://dx.doi.org/10.2147/IJN.S338064 |
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author | Khan, Muhammad Khalid Khan, Barkat Ali Uzair, Bushra Iram Niaz, Shah Khan, Haroon Hosny, Khaled Mohamed Menaa, Farid |
author_facet | Khan, Muhammad Khalid Khan, Barkat Ali Uzair, Bushra Iram Niaz, Shah Khan, Haroon Hosny, Khaled Mohamed Menaa, Farid |
author_sort | Khan, Muhammad Khalid |
collection | PubMed |
description | PURPOSE: Microbial resistance to antibiotics is one of the most important public health concerns of the 21(st) century. We isolated, purified, and structurally elucidated antifungal secondary metabolites from red soil microbes and encapsulated them into chitosan (CS)-based nanoemulsion (NE) gel (NEG). METHODS: Three compounds were isolated and purified of which only one compound (Pure 2) showed potent antifungal activity (MFC: 8–132 µg/mL), which was also significantly (P<0.05) more efficient than fluconazole (MFC: 32–132 µg/mL). Pure 2 was structurally elucidated using 1D- and 2D-NMR before its incorporation into NEG. The formulations were prepared by high-speed homogenization technique. Physicochemical and pharmacological characterizations of formulations (ie, droplet size, PDI, zeta potential, drug content, viscosity, SEM, FTIR, spreadability, in vitro drug release, ex vivo permeation, in vitro antifungal and in vivo antifungal activities) were assessed. RESULTS: NMR analyses identified the compound as a derivative of phthalic acid ester (PAE). The optimized formulations displayed a droplet size <100 nm, -ve zeta potential, and PDI <0.45. The drug content was within the official limit of pharmacopeia (ie, 100±10%). Insignificant changes (P>0.05) in the viscosity of the formulations stored were observed. The morphology of the formulations indicated mesh-like structure. The FTIR study indicated that there were no interactions between the drug and other ingredients of the formulations. Optimum spreadability was observed in all formulations. NEG released 75.3±1.12% of Pure 2 after 12 hrs while NE released 85.33±1.88% of the compound. The skin permeation of F2 (71.15±1.28%) was significantly different (P<0.05) from F3 (81.80±1.91%) in rabbits. Complete and apparently safe recovery from the fungal infection was achieved in rabbits treated topically with Pure 2-loaded NEGs. CONCLUSION: Hence, the NEG-loaded PAE isolated from Pseudomonas fluorescens represents a possible alternative for the treatment of fungal infections as compared to available therapies. |
format | Online Article Text |
id | pubmed-8689013 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-86890132021-12-22 Development of Chitosan-Based Nanoemulsion Gel Containing Microbial Secondary Metabolite with Effective Antifungal Activity: In vitro and in vivo Characterizations Khan, Muhammad Khalid Khan, Barkat Ali Uzair, Bushra Iram Niaz, Shah Khan, Haroon Hosny, Khaled Mohamed Menaa, Farid Int J Nanomedicine Original Research PURPOSE: Microbial resistance to antibiotics is one of the most important public health concerns of the 21(st) century. We isolated, purified, and structurally elucidated antifungal secondary metabolites from red soil microbes and encapsulated them into chitosan (CS)-based nanoemulsion (NE) gel (NEG). METHODS: Three compounds were isolated and purified of which only one compound (Pure 2) showed potent antifungal activity (MFC: 8–132 µg/mL), which was also significantly (P<0.05) more efficient than fluconazole (MFC: 32–132 µg/mL). Pure 2 was structurally elucidated using 1D- and 2D-NMR before its incorporation into NEG. The formulations were prepared by high-speed homogenization technique. Physicochemical and pharmacological characterizations of formulations (ie, droplet size, PDI, zeta potential, drug content, viscosity, SEM, FTIR, spreadability, in vitro drug release, ex vivo permeation, in vitro antifungal and in vivo antifungal activities) were assessed. RESULTS: NMR analyses identified the compound as a derivative of phthalic acid ester (PAE). The optimized formulations displayed a droplet size <100 nm, -ve zeta potential, and PDI <0.45. The drug content was within the official limit of pharmacopeia (ie, 100±10%). Insignificant changes (P>0.05) in the viscosity of the formulations stored were observed. The morphology of the formulations indicated mesh-like structure. The FTIR study indicated that there were no interactions between the drug and other ingredients of the formulations. Optimum spreadability was observed in all formulations. NEG released 75.3±1.12% of Pure 2 after 12 hrs while NE released 85.33±1.88% of the compound. The skin permeation of F2 (71.15±1.28%) was significantly different (P<0.05) from F3 (81.80±1.91%) in rabbits. Complete and apparently safe recovery from the fungal infection was achieved in rabbits treated topically with Pure 2-loaded NEGs. CONCLUSION: Hence, the NEG-loaded PAE isolated from Pseudomonas fluorescens represents a possible alternative for the treatment of fungal infections as compared to available therapies. Dove 2021-12-16 /pmc/articles/PMC8689013/ /pubmed/34949923 http://dx.doi.org/10.2147/IJN.S338064 Text en © 2021 Khan et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Khan, Muhammad Khalid Khan, Barkat Ali Uzair, Bushra Iram Niaz, Shah Khan, Haroon Hosny, Khaled Mohamed Menaa, Farid Development of Chitosan-Based Nanoemulsion Gel Containing Microbial Secondary Metabolite with Effective Antifungal Activity: In vitro and in vivo Characterizations |
title | Development of Chitosan-Based Nanoemulsion Gel Containing Microbial Secondary Metabolite with Effective Antifungal Activity: In vitro and in vivo Characterizations |
title_full | Development of Chitosan-Based Nanoemulsion Gel Containing Microbial Secondary Metabolite with Effective Antifungal Activity: In vitro and in vivo Characterizations |
title_fullStr | Development of Chitosan-Based Nanoemulsion Gel Containing Microbial Secondary Metabolite with Effective Antifungal Activity: In vitro and in vivo Characterizations |
title_full_unstemmed | Development of Chitosan-Based Nanoemulsion Gel Containing Microbial Secondary Metabolite with Effective Antifungal Activity: In vitro and in vivo Characterizations |
title_short | Development of Chitosan-Based Nanoemulsion Gel Containing Microbial Secondary Metabolite with Effective Antifungal Activity: In vitro and in vivo Characterizations |
title_sort | development of chitosan-based nanoemulsion gel containing microbial secondary metabolite with effective antifungal activity: in vitro and in vivo characterizations |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8689013/ https://www.ncbi.nlm.nih.gov/pubmed/34949923 http://dx.doi.org/10.2147/IJN.S338064 |
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