Thermosensitive In Situ Ophthalmic Gel for Effective Local Delivery and Antifungal Activity of Ketoconazole Nanoparticles
Fungal keratitis is a severe ocular infection caused by pathogenic fungi, leading to potential vision loss if untreated. Current antifungal treatments face limitations such as low solubility, poor corneal penetration, and limited therapeutic options. This study aimed to develop a thermosensitive in...
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MDPI AG
2024-12-01
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| author | Chutima Chaiwut Sarin Tadtong Puriputt Akachaipaibul Jutamas Jiaranaikulwanitch Sudarshan Singh Siriporn Okonogi Dwi Marlina Syukri Chuda Chittasupho |
| author_facet | Chutima Chaiwut Sarin Tadtong Puriputt Akachaipaibul Jutamas Jiaranaikulwanitch Sudarshan Singh Siriporn Okonogi Dwi Marlina Syukri Chuda Chittasupho |
| author_sort | Chutima Chaiwut |
| collection | DOAJ |
| description | Fungal keratitis is a severe ocular infection caused by pathogenic fungi, leading to potential vision loss if untreated. Current antifungal treatments face limitations such as low solubility, poor corneal penetration, and limited therapeutic options. This study aimed to develop a thermosensitive in situ gel incorporating ketoconazole nanoparticles (NPs) to enhance drug solubility, stability, and antifungal activity. Ketoconazole NPs were prepared using the solvent displacement method, achieving a particle size of 198.25 ± 27.51 nm, encapsulation efficiency of 94.08 ± 0.51%, polydispersity index of 0.42 ± 0.08, and a positive zeta potential value of +10.08 ± 0.19 mV. The NPs exhibited sustained zero-order release kinetics. The optimized NPs were incorporated into a poloxamer-based in situ gel, demonstrating a gelation temperature of 34.67 ± 0.58 °C and the shortest gelation time. The formulation provided a 5-fold increase in solubility and a 10-fold improvement in drug release compared to pure ketoconazole. Stability studies confirmed the gel retained its physicochemical and rheological properties for three months under various storage conditions. The in situ gel showed sustained release, effective antifungal activity against <i>Malassezia furfur</i>, and good tolerability, suggesting it as a promising alternative for treating fungal keratitis with improved bioavailability and patient compliance. |
| format | Article |
| id | doaj-art-6841d31a0956481a8cb16cb6b3246dbe |
| institution | Kabale University |
| issn | 2310-2861 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Gels |
| spelling | doaj-art-6841d31a0956481a8cb16cb6b3246dbe2025-01-24T13:33:45ZengMDPI AGGels2310-28612024-12-011111310.3390/gels11010013Thermosensitive In Situ Ophthalmic Gel for Effective Local Delivery and Antifungal Activity of Ketoconazole NanoparticlesChutima Chaiwut0Sarin Tadtong1Puriputt Akachaipaibul2Jutamas Jiaranaikulwanitch3Sudarshan Singh4Siriporn Okonogi5Dwi Marlina Syukri6Chuda Chittasupho7Master’s Degree Program in Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, ThailandFaculty of Pharmacy, Srinakharinwirot University, Nakhonnayok 26120, ThailandFaculty of Pharmacy, Srinakharinwirot University, Nakhonnayok 26120, ThailandDepartment of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, ThailandCenter of Excellence in Pharmaceutical Nanotechnology, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Microbiology, Faculty of Medicine, Malahayati University, Lampung 35153, IndonesiaDepartment of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, ThailandFungal keratitis is a severe ocular infection caused by pathogenic fungi, leading to potential vision loss if untreated. Current antifungal treatments face limitations such as low solubility, poor corneal penetration, and limited therapeutic options. This study aimed to develop a thermosensitive in situ gel incorporating ketoconazole nanoparticles (NPs) to enhance drug solubility, stability, and antifungal activity. Ketoconazole NPs were prepared using the solvent displacement method, achieving a particle size of 198.25 ± 27.51 nm, encapsulation efficiency of 94.08 ± 0.51%, polydispersity index of 0.42 ± 0.08, and a positive zeta potential value of +10.08 ± 0.19 mV. The NPs exhibited sustained zero-order release kinetics. The optimized NPs were incorporated into a poloxamer-based in situ gel, demonstrating a gelation temperature of 34.67 ± 0.58 °C and the shortest gelation time. The formulation provided a 5-fold increase in solubility and a 10-fold improvement in drug release compared to pure ketoconazole. Stability studies confirmed the gel retained its physicochemical and rheological properties for three months under various storage conditions. The in situ gel showed sustained release, effective antifungal activity against <i>Malassezia furfur</i>, and good tolerability, suggesting it as a promising alternative for treating fungal keratitis with improved bioavailability and patient compliance.https://www.mdpi.com/2310-2861/11/1/13ophthalmic preparationin situ gelantifungal drugsextemporaneous preparation |
| spellingShingle | Chutima Chaiwut Sarin Tadtong Puriputt Akachaipaibul Jutamas Jiaranaikulwanitch Sudarshan Singh Siriporn Okonogi Dwi Marlina Syukri Chuda Chittasupho Thermosensitive In Situ Ophthalmic Gel for Effective Local Delivery and Antifungal Activity of Ketoconazole Nanoparticles Gels ophthalmic preparation in situ gel antifungal drugs extemporaneous preparation |
| title | Thermosensitive In Situ Ophthalmic Gel for Effective Local Delivery and Antifungal Activity of Ketoconazole Nanoparticles |
| title_full | Thermosensitive In Situ Ophthalmic Gel for Effective Local Delivery and Antifungal Activity of Ketoconazole Nanoparticles |
| title_fullStr | Thermosensitive In Situ Ophthalmic Gel for Effective Local Delivery and Antifungal Activity of Ketoconazole Nanoparticles |
| title_full_unstemmed | Thermosensitive In Situ Ophthalmic Gel for Effective Local Delivery and Antifungal Activity of Ketoconazole Nanoparticles |
| title_short | Thermosensitive In Situ Ophthalmic Gel for Effective Local Delivery and Antifungal Activity of Ketoconazole Nanoparticles |
| title_sort | thermosensitive in situ ophthalmic gel for effective local delivery and antifungal activity of ketoconazole nanoparticles |
| topic | ophthalmic preparation in situ gel antifungal drugs extemporaneous preparation |
| url | https://www.mdpi.com/2310-2861/11/1/13 |
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