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3D Printable Alginate-Chitosan Hydrogel Loaded With Ketoconazole Exhibits Anticryptococcal Activity
Manoela Almeida Martins Mace1,2,3, Camila Leites Reginatto3,4, Victória Rapack Jacinto Silva5,6
1Programa de Pós-Graduação Em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
Abstract:
Natural polymers have recently been investigated for various applications, such as 3D printing and healthcare, including treating infections. Among microbial infections, fungal diseases remain overlooked, with limited therapeutic options and high recurrence. Cutaneous cryptococcosis is an opportunistic fungal infection triggered by mechanical inoculation or hematogenous dissemination of the yeast that causes cryptococcal pneumonia and meningitis. Every year, Cryptococcus neoformans endanger the lives of immunosuppressed hosts, resulting in 180,000 deaths per year. Nonetheless, healthy individuals can also be affected by this fungal infection. Cryptococcosis has a restricted and expensive therapeutic regimen with no topical approach to skin manifestations. This study sought to create a 3D printable biodegradable polymeric hydrogel carrying ketoconazole, a low-cost antifungal drug with reported anticryptococcal activity. The developed hydrogel exhibited good 3D printability and rheological properties, including a pseudoplastic behavior. The FTIR spectra of cross-linked hydrogels revealed interactions between alginate and Ca+2, referred to as the egg-box model, indicated by the decrease in peaks at 1600 and 1410 cm-1. Furthermore, the hydrogel loaded with ketoconazole showed remarkable antifungal activity against C. neoformans strains indicated by inhibition zones, which cross-linking did not seem to affect its antifungal performance. The developed material remained structurally stable for up to 12 days (288 h) in swelling studies, and preliminary cytotoxicity performed with V79 cells indicates potential for in vivo studies and topical application.
Insights
Researchers developed a 3D printable hydrogel for treating fungal skin infections. This biodegradable material effectively delivered ketoconazole, showing potent antifungal activity against Cryptococcus neoformans.
Area of Science:
- Biomaterials Science
- Mycology
- Drug Delivery Systems
Background:
- Fungal infections, particularly cutaneous cryptococcosis caused by Cryptococcus neoformans, present limited therapeutic options and high recurrence rates.
- Current treatments for cryptococcosis are often systemic, expensive, and lack topical approaches for skin manifestations, impacting 180,000 lives annually.
- Natural polymers are being explored for advanced applications in healthcare, including infection treatment.
Purpose of the Study:
- To develop a 3D printable, biodegradable polymeric hydrogel for topical delivery of ketoconazole.
- To assess the printability, rheological properties, and antifungal efficacy of the ketoconazole-loaded hydrogel against Cryptococcus neoformans.
- To evaluate the stability and preliminary cytotoxicity of the developed hydrogel for potential in vivo applications.
Main Methods:
- Fabrication of a 3D printable biodegradable polymeric hydrogel loaded with ketoconazole.
- Characterization of hydrogel properties including 3D printability, rheology (pseudoplastic behavior), and FTIR spectra to confirm alginate-Ca+2 interactions (egg-box model).
- Assessment of antifungal activity against C. neoformans strains via inhibition zones and evaluation of material stability through swelling studies and preliminary cytotoxicity tests using V79 cells.
Main Results:
- The developed hydrogel demonstrated excellent 3D printability and desirable pseudoplastic rheological properties.
- FTIR analysis confirmed cross-linking via the alginate-Ca+2 egg-box model.
- The ketoconazole-loaded hydrogel exhibited significant antifungal activity against C. neoformans, with stability up to 12 days and promising preliminary cytotoxicity results.
Conclusions:
- A 3D printable, biodegradable hydrogel loaded with ketoconazole was successfully developed.
- The hydrogel formulation shows potent antifungal activity against Cryptococcus neoformans, suitable for topical application.
- The material's stability and preliminary safety profile suggest its potential for further in vivo studies and clinical translation for cutaneous fungal infections.
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