Development, Safety, and Therapeutic Evaluation of Voriconazole-Loaded Zein–Pectin–Hyaluronic Acid Nanoparticles Using Alternative In Vivo Models for Efficacy and Toxicity
<b>Background/Objectives</b>: Fungal infections caused by <i>Candida</i> species remain a significant clinical challenge, exacerbated by limitations in current antifungal therapies, including toxicity and poor bioavailability. This study aimed to develop and evaluate voricona...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-02-01
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| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/17/2/231 |
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| Summary: | <b>Background/Objectives</b>: Fungal infections caused by <i>Candida</i> species remain a significant clinical challenge, exacerbated by limitations in current antifungal therapies, including toxicity and poor bioavailability. This study aimed to develop and evaluate voriconazole-loaded zein–pectin–hyaluronic acid nanoparticles (ZPHA-VRC NPs) as a novel drug delivery system to enhance efficacy and reduce toxicity. Alternative in vitro and in vivo models were utilized to assess the safety and therapeutic potential of the nanoparticles. <b>Methods</b>: ZPHA-VRC NPs were prepared using a nanoprecipitation method and characterized for particle size, polydispersity index, zeta potential, and encapsulation efficiency. Antifungal activity was assessed via MIC assays against <i>Candida albicans</i>, <i>C. krusei</i>, and <i>C. parapsilosis</i>. Cytotoxicity was evaluated on Vero cells, while in vivo toxicity and efficacy were assessed using <i>Galleria mellonella</i> and <i>Caenorhabditis elegans</i> models. The therapeutic efficacy was further evaluated in an infected <i>Caenorhabditis elegans</i> model using survival and health scores. <b>Results</b>: ZPHA-VRC nanoparticles exhibited favorable physicochemical properties, including a particle size of approximately 192 nm, a polydispersity index of 0.079, a zeta potential of −24 mV, and an encapsulation efficiency of 34%. The nanoparticles retained antifungal activity comparable to free voriconazole while significantly reducing cytotoxicity. In vivo studies using <i>G. mellonella</i> and <i>C. elegans</i> demonstrated that ZPHA-VRC NPs markedly improved survival rates, reduced fungal burden, and enhanced health scores in infected models, outperforming the free drug. Additionally, the nanoparticles exhibited a superior safety profile, minimizing systemic toxicity while maintaining therapeutic efficacy. <b>Conclusions</b>: ZPHA-VRC NPs offer a safer and more effective delivery system for VRC, addressing the limitations of conventional formulations. The integration of alternative efficacy and safety models highlights their value in preclinical research. |
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| ISSN: | 1999-4923 |