3D Printable Alginate-Chitosan Hydrogel Loaded With Ketoconazole Exhibits Anticryptococcal Activity.

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.