Synthesis and Evaluation of a Chitosan-Based Cationic Hydrogel with Strong Antifungal and Antibiofilm Activities Against Clinical Isolates of Candida auris
Abstract
1. Introduction
2. Results
2.1. Culture, Identification, and ASFT of Isolates
2.2. Synthesis of Hydrogel
2.3. Zeta Size, Potential, and Polydispersity Index (PDI)
2.4. Scanning Electron Microscope (SEM)
2.5. Fourier Transform Infrared (FT-IR) Spectroscopy
2.6. Thermogravimetric Analysis (TGA)
2.7. Swelling and Degradation Assay of Hydrogel
2.8. Drug Entrapment Efficiency (%DEE) and Release Kinetics
2.9. Antifungal Activity of Hydrogel
2.10. CFW Staining and Fluorescent Microscopy of C. auris Cells Treated with Hydrogel
2.11. Hemocompatibility Assay
2.12. Biofilm Assay
2.13. In Silico Analysis
2.13.1. Molecular Properties and Drug Likeness
2.13.2. In Silico Interaction with Cytochrome Enzymes
2.13.3. Toxicity Prediction
2.13.4. Nuclear Receptor Signaling Pathway Toxicity Prediction
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Isolation and Identification of C. auris
4.3. Antifungal Susceptibility Testing
4.4. Synthesis of Hydrogel
4.5. Characterization of Hydrogel
4.5.1. Zeta Potential and PDI Measurement
4.5.2. Morphological Studies
4.5.3. Fourier Transform Infrared (FT-IR) Spectroscopy
4.5.4. Thermogravimetric Analysis
4.6. Swelling and Degradation Assay of Hydrogel
4.7. Drug Entrapment Efficiency (%DEE) of Hydrogel
4.8. Antifungal Activity of Hydrogel
4.9. Calcofluor White Staining and Fluorescent Microscopy of C. auris Cells
4.10. Hemocompatibility Assay of Hydrogel
4.11. Biofilm Assay
4.12. In Silico Analysis
4.13. Data Analysis
5. Conclusions and Future Recommendations
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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pH | Release Medium | Zero-Order Kinetics | First-Order Kinetics | Korsemeyer–Peppas Model | Mechanism of Drug Release | |||
---|---|---|---|---|---|---|---|---|
R2 | K0 | R2 | K1 | R2 | n | |||
4.0 | Acetate buffer | 0.894 | 0.120 | 0.846 | 0.009 | 0.967 | 0.54 | Non-Fickian diffusion |
7.4 | Phosphate-buffered saline (PBS) | 0.958 | 0.113 | 0.942 | 0.006 | 0.974 | 0.75 | Non-Fickian diffusion |
10 | Borate buffer | 0.894 | 0.122 | 0.854 | 0.008 | 0.978 | 0.59 | Non-Fickian diffusion |
Tested Items | CS | PEG | MAA |
---|---|---|---|
Log P | 0.88 | −1.03 | 0.65 |
TPSA (Å) | 56.79 | 40.46 | 37.30 |
HBDs | 1 | 2 | 1 |
HBAs | 5 | 2 | 2 |
MW (g/mol) | 184.1 | 62.07 | 86.1 |
nRT | 4 | 1 | 1 |
PAINS | 0 | 0 | 0 |
Bioavailability score | 0.55 | 0.55 | 0.85 |
Synthetic accessibility | 3.14 | 1.00 | 1.01 |
Lepinski rule | Yes (0) | Yes (0) | Yes (0) |
Veber rule | Yes | Yes | Yes |
Tested Items | CS | PEG | MAA |
---|---|---|---|
CYP2C19 inhibitor | No | No | No |
CYP3A4 inhibitor | No | No | No |
CYP1A2 inhibitor | No | No | No |
CYP2C9 inhibitor | No | No | No |
CYP2D6 inhibitor | No | No | No |
Tested Items | CS | PEG | MAA |
---|---|---|---|
Predicted LD50 (mg/kg) | 1000 | 4700 | 118 |
Toxicity class | 4 | 5 | 3 |
Neurotoxicity | Inactive (0.50) | Inactive (0.90) | Inactive (0.62) |
Hepatotoxicity | Inactive (0.77) | Inactive (0.80) | Inactive (0.65) |
Carcinogenicity | Inactive (0.58) | Inactive (0.79) | Inactive (0.78) |
Respiratory toxicity | Active (0.57) | Inactive (0.57) | Inactive (0.87) |
Mutagenicity | Inactive (0.64) | Inactive (0.89) | Inactive (0.89) |
Tested Items | CS | PEG | MAA |
---|---|---|---|
AhR | Inactive (0.96) | Inactive (0.97) | Inactive (1.0) |
AR | Inactive (0.98) | Inactive (0.98) | Inactive (1.0) |
AR-LBD | Inactive (0.98) | Inactive (0.96) | Inactive (0.99) |
Aromatase | Inactive (0.94) | Inactive (1.0) | Inactive (1.0) |
ER | Inactive (0.89) | Inactive (0.91) | Inactive (0.90) |
ER-LBD | Inactive 0.97) | Inactive (0.98) | Inactive (1.0) |
PPAR-Gamma | Inactive (0.95) | Inactive (0.95) | Inactive (0.99) |
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Kamran, M.; Aftab, M.; Amir, A.; Javed, F.; Latif, A.Q.; Saldera, K.A.; Ahad, A.; Jardan, Y.A.B.; Walker, L.A.; Nisa, K.; et al. Synthesis and Evaluation of a Chitosan-Based Cationic Hydrogel with Strong Antifungal and Antibiofilm Activities Against Clinical Isolates of Candida auris. Pharmaceuticals 2025, 18, 506. https://doi.org/10.3390/ph18040506
Kamran M, Aftab M, Amir A, Javed F, Latif AQ, Saldera KA, Ahad A, Jardan YAB, Walker LA, Nisa K, et al. Synthesis and Evaluation of a Chitosan-Based Cationic Hydrogel with Strong Antifungal and Antibiofilm Activities Against Clinical Isolates of Candida auris. Pharmaceuticals. 2025; 18(4):506. https://doi.org/10.3390/ph18040506
Chicago/Turabian StyleKamran, Muhammad, Maryam Aftab, Afreenish Amir, Fatima Javed, Amtul Quddos Latif, Kausar Abbas Saldera, Abdul Ahad, Yousef A. Bin Jardan, Louise Ann Walker, Kiran Nisa, and et al. 2025. "Synthesis and Evaluation of a Chitosan-Based Cationic Hydrogel with Strong Antifungal and Antibiofilm Activities Against Clinical Isolates of Candida auris" Pharmaceuticals 18, no. 4: 506. https://doi.org/10.3390/ph18040506
APA StyleKamran, M., Aftab, M., Amir, A., Javed, F., Latif, A. Q., Saldera, K. A., Ahad, A., Jardan, Y. A. B., Walker, L. A., Nisa, K., Ullah, F., & Shah, N. A. (2025). Synthesis and Evaluation of a Chitosan-Based Cationic Hydrogel with Strong Antifungal and Antibiofilm Activities Against Clinical Isolates of Candida auris. Pharmaceuticals, 18(4), 506. https://doi.org/10.3390/ph18040506