Antifungal nanoparticles for targeted treatment of fungal infections
a technology of nanoparticles and antifungal agents, which is applied in the direction of pharmaceutical non-active ingredients, cyclic peptide ingredients, medical preparations, etc., can solve the problems of limiting clinically viable therapeutic options, increasing the severity of fungal infections, and recurring infections, so as to reduce the burden of fungal infections, improve the efficacy of antifungal biofilms, and improve the effect of antifungal
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example 1
Fabricating Additional Antifungal Nanoparticle Formulations to Confirm In Vitro Activity
[0060]Motivated by the success of the anidulafungin-incorporating liposomes, this Example examines the fabrication of other nanoparticle formulations using the same lipid composition but incorporating different antifungal drugs. To complete the in vivo characterization of the liposomal therapeutics that the inventors have developed and characterized, including the anidulafungin liposome formulations but also including formulations of other antifungal liposomes based upon this work, the inventors are generating a library of antifungal nanoparticles. The inventors are investigating the in vitro and in vivo efficacy of these additional formulations, providing the data to enable clinical translation. The inventors are also examining the stability and scale-up of these liposomal formulations to enhance treatment options for fungal infections.
[0061]The efficacy of a library of antifungal encapsulating ...
example 2
Nanoparticle Activity and Toxicity In Vivo in Systemic Fungal Infections
[0063]The objective of this Example is to determine the efficacy of the liposomal antifungal formulations in reducing systemic Candida burden and off-site toxicity compared to free drug in Galleria mellonella (wax moth) larvae and murine infection models, which have been widely used to study the pathogenic mechanisms of Candida albicans.
[0064]Initially, the liposome library can be tested in Galleria mellonella larvae, which are used in infection models due to their cellular and humoral innate immune response, which correlates with mammalian responses to virulence. See, Jiang et al., J. Controlled Release, 279, 316-325 (2018); Tsai et al., Virulence, 7(3), 214-229 (2016). Healthy larvae of similar size are injected in the last left proleg using a 29-gauge needle with five μL of wild-type Candida albicans (5×10{circumflex over ( )}5 CFU) in sterile saline. This concentration kills Galleria mellonella larvae withi...
example 3
Nanoparticle Scale-Up and Storage Stability
[0068]Liposome fabrication occurs in aqueous conditions. Liposomes or encapsulated therapeutics can disrupt overtime. To store these liposomes or encapsulated therapeutics for extended periods (i.e., years), those having ordinary skill in the liposome formulation art should use methods of drying the formulations that do not compromise vesicle structure. Different cryoprotectants and lyoprotectants should be used as additives to protect the liposomes during freeze-drying and prolonged storage.
[0069]Scaling liposome production is important for a successful clinical translation. Those having ordinary skill in the liposome formulation art can use established expertise in pharmaceutical and liposomal storage and scale-up, to enable robust characterization of the antifungal formulations developed (i.e., anidulafungin liposomes) for translation and fabrication of additional formulations.
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