Invasive aspergillosis is a serious threat to immunodeficient and critically ill patients caused mainly by the fungus Aspergillus fumigatus. Here, poly(glycidol)-based nanogels (NGs) are proposed as delivery vehicles for antifungal agents for sustained drug release. NGs are formed by simple self-assembly of random copolymers, followed by oxidative cross-linking of thiol functionalities. We investigate the impact of copolymer amphiphilicity on NG interaction with mature fungal hyphae in order to select the optimal drug delivery system for model antifungal drug amphotericin B. The results show that drug-loaded NGs decrease minimal inhibitory concentration (MIC) for around four times and slow down the fungal biofilm synthesis at concentrations lower than MIC. Our results suggest that amphiphilicity of nanoparticle's polymer matrix is an important factor in understanding the action of nanocarriers toward fungal cells and should be considered in the development of nanoparticle-based antifungal therapy.
Aspergillus fumigatus is the opportunistic fungus responsible for a variety of serious and often lethal diseases of immunocompromised patients, such as invasive aspergillosis, aspergilloma, and allergic bronchopulmonary aspergillosis. Therapeutic options for such fungal infections are limited due to the high toxicity of currently available drugs. Herein, the potency of nanogels (NGs) is assessed for uptake and delivery of antifungal therapeutics. Therefore, poly(glycidol)‐based NGs are prepared by surfactant‐free inverse nanoprecipitation. Uptake studies conducted with fluorescently labeled particles demonstrate internalization by fungi in their hyphal form. In addition, loading with both amphiphilic and hydrophobic fluorescent dyes as model drugs show efficient delivery of the fluorescent dyes into the fungus. Finally, particles are loaded with the antifungal drug itraconazole by soaking lyophilized NGs in the drug solution (breathing‐in method). Efficient delivery of the drug by nanoprecipitated NGs, improved fungicidal activity, and reduced side effects as compared with the drug itself are shown.
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