Synthesis and Evaluation of a Chitosan-Based Cationic Hydrogel with Strong Antifungal and Antibiofilm Activities Against Clinical Isolates of <i>Candida auris</i>
<b>Background: </b><i>Candida auris</i> is a significant global health concern, due to its rapid transmission, high mortality rate, and resistance to commonly available antifungal drugs. <b>Methodology:</b> During the current study, a cationic polymeric hydrogel w...
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MDPI AG
2025-03-01
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| author | Muhammad Kamran Maryam Aftab Afreenish Amir Fatima Javed Amtul Quddos Latif Kausar Abbas Saldera Abdul Ahad Yousef A. Bin Jardan Louise Ann Walker Kiran Nisa Faheem Ullah Naseer Ali Shah |
| author_facet | Muhammad Kamran Maryam Aftab Afreenish Amir Fatima Javed Amtul Quddos Latif Kausar Abbas Saldera Abdul Ahad Yousef A. Bin Jardan Louise Ann Walker Kiran Nisa Faheem Ullah Naseer Ali Shah |
| author_sort | Muhammad Kamran |
| collection | DOAJ |
| description | <b>Background: </b><i>Candida auris</i> is a significant global health concern, due to its rapid transmission, high mortality rate, and resistance to commonly available antifungal drugs. <b>Methodology:</b> During the current study, a cationic polymeric hydrogel was developed using chitosan (CS), polyethylene glycol (PEG), and methacrylic acid (MAA). The respective solutions were mixed in a volumetric ratio of 2:1:1. After characterization, the hydrogel was assessed using antifungal, antibiofilm, and hemocompatibility assays. <b>Results:</b> The hydrodynamic radius of 554.7 ± 90.1 nm and zeta potential of 15.6 ± 1.09 mV indicate the ideal size and charge for topical applications and in vivo studies, respectively. The formulation exhibited improved thermal stability, enhanced swelling, and a drug release profile for non-Fickian diffusion. The hydrogel effectively inhibited fungal growth in agar plates (42 ± 7.31 mm zone of inhibition), with a mean IC<sub>50</sub> of 15.17 ± 4.01 μg/mL and MIC of 29.30 ± 11.72 μg/mL. Calcofluor white (CFW) staining showed diffuse irregular yeast cells, suggesting increased membrane permeability, eventually leading to cell death. The hemocompatibility assay revealed no visible agglutination or hemolysis at the MIC value. The formulation exhibited significantly reduced biofilm formation compared to the growth control (<i>p</i> < 0.05). Additionally, in silico analysis revealed that MAA showed superior oral bioavailability, no inhibitory activity on cytochrome P450 enzymes, and low potential for toxicity through nuclear receptor signaling pathways. <b>Conclusions:</b> Cationic hydrogels show promise as potential antifungal treatments. The development of cost-effective and improved therapeutic methods is crucial to combat this deadly pathogen and to improve patient outcomes. |
| format | Article |
| id | doaj-art-4d27833746ff48b09d3729fc090d0526 |
| institution | DOAJ |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-4d27833746ff48b09d3729fc090d05262025-08-20T03:13:58ZengMDPI AGPharmaceuticals1424-82472025-03-0118450610.3390/ph18040506Synthesis and Evaluation of a Chitosan-Based Cationic Hydrogel with Strong Antifungal and Antibiofilm Activities Against Clinical Isolates of <i>Candida auris</i>Muhammad Kamran0Maryam Aftab1Afreenish Amir2Fatima Javed3Amtul Quddos Latif4Kausar Abbas Saldera5Abdul Ahad6Yousef A. Bin Jardan7Louise Ann Walker8Kiran Nisa9Faheem Ullah10Naseer Ali Shah11Department of Biosciences, COMSATS University Islamabad, Islamabad 45520, PakistanDepartment of Biosciences, COMSATS University Islamabad, Islamabad 45520, PakistanDepartment of Pathology, Rawalpindi Medical University, Rawalpindi 46000, PakistanDepartment of Chemistry, Shaheed Benazir Bhutto Women University, Peshawar 25000, PakistanJinnah Post Graduate Medical Centre, Karachi 77550, PakistanJinnah Post Graduate Medical Centre, Karachi 77550, PakistanDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaSchool of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UKDepartment of Biosciences, COMSATS University Islamabad, Islamabad 45520, PakistanBioresource Technology Division, School of Industrial Technology, Universiti Sains Malaysia, Gelugor 11800, Pulau Pinang, MalaysiaDepartment of Biosciences, COMSATS University Islamabad, Islamabad 45520, Pakistan<b>Background: </b><i>Candida auris</i> is a significant global health concern, due to its rapid transmission, high mortality rate, and resistance to commonly available antifungal drugs. <b>Methodology:</b> During the current study, a cationic polymeric hydrogel was developed using chitosan (CS), polyethylene glycol (PEG), and methacrylic acid (MAA). The respective solutions were mixed in a volumetric ratio of 2:1:1. After characterization, the hydrogel was assessed using antifungal, antibiofilm, and hemocompatibility assays. <b>Results:</b> The hydrodynamic radius of 554.7 ± 90.1 nm and zeta potential of 15.6 ± 1.09 mV indicate the ideal size and charge for topical applications and in vivo studies, respectively. The formulation exhibited improved thermal stability, enhanced swelling, and a drug release profile for non-Fickian diffusion. The hydrogel effectively inhibited fungal growth in agar plates (42 ± 7.31 mm zone of inhibition), with a mean IC<sub>50</sub> of 15.17 ± 4.01 μg/mL and MIC of 29.30 ± 11.72 μg/mL. Calcofluor white (CFW) staining showed diffuse irregular yeast cells, suggesting increased membrane permeability, eventually leading to cell death. The hemocompatibility assay revealed no visible agglutination or hemolysis at the MIC value. The formulation exhibited significantly reduced biofilm formation compared to the growth control (<i>p</i> < 0.05). Additionally, in silico analysis revealed that MAA showed superior oral bioavailability, no inhibitory activity on cytochrome P450 enzymes, and low potential for toxicity through nuclear receptor signaling pathways. <b>Conclusions:</b> Cationic hydrogels show promise as potential antifungal treatments. The development of cost-effective and improved therapeutic methods is crucial to combat this deadly pathogen and to improve patient outcomes.https://www.mdpi.com/1424-8247/18/4/506<i>Candida auris</i>antimicrobial resistanceantifungal activitybiofilmcandidemiachitosan |
| spellingShingle | Muhammad Kamran Maryam Aftab Afreenish Amir Fatima Javed Amtul Quddos Latif Kausar Abbas Saldera Abdul Ahad Yousef A. Bin Jardan Louise Ann Walker Kiran Nisa Faheem Ullah Naseer Ali Shah Synthesis and Evaluation of a Chitosan-Based Cationic Hydrogel with Strong Antifungal and Antibiofilm Activities Against Clinical Isolates of <i>Candida auris</i> Pharmaceuticals <i>Candida auris</i> antimicrobial resistance antifungal activity biofilm candidemia chitosan |
| title | Synthesis and Evaluation of a Chitosan-Based Cationic Hydrogel with Strong Antifungal and Antibiofilm Activities Against Clinical Isolates of <i>Candida auris</i> |
| title_full | Synthesis and Evaluation of a Chitosan-Based Cationic Hydrogel with Strong Antifungal and Antibiofilm Activities Against Clinical Isolates of <i>Candida auris</i> |
| title_fullStr | Synthesis and Evaluation of a Chitosan-Based Cationic Hydrogel with Strong Antifungal and Antibiofilm Activities Against Clinical Isolates of <i>Candida auris</i> |
| title_full_unstemmed | Synthesis and Evaluation of a Chitosan-Based Cationic Hydrogel with Strong Antifungal and Antibiofilm Activities Against Clinical Isolates of <i>Candida auris</i> |
| title_short | Synthesis and Evaluation of a Chitosan-Based Cationic Hydrogel with Strong Antifungal and Antibiofilm Activities Against Clinical Isolates of <i>Candida auris</i> |
| title_sort | synthesis and evaluation of a chitosan based cationic hydrogel with strong antifungal and antibiofilm activities against clinical isolates of i candida auris i |
| topic | <i>Candida auris</i> antimicrobial resistance antifungal activity biofilm candidemia chitosan |
| url | https://www.mdpi.com/1424-8247/18/4/506 |
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