Synthesis and characterization of amphiphilic dendronized polyglycerol for delivery of amphotericin B in Candida spp. infections

Aim and Background: Systemic fungal infections are a significant public health concern that affects a large population of immunocompromised individuals. Amphotericin B (AMB) is an effective antifungal drug used for treating a wide range of fungal infections. However, the clinical use of AMB is limited due to its serious side effects such as hemolysis, nephrotoxicity, and hepatotoxicity. Nanoscale polymeric assemblies have been shown to improve the solubility and toxicity of poorly soluble drugs. Methods: In this study, cholesterol-based dendritic micellar assemblies of hyperbranched polyglycerol (HPG) nanostructures were developed for AMB delivery. The drug loading and release profile of AMB in dendritic micelle formulations was evaluated. Following that, toxicity, antifungal activities, and biofilm formation inhibitory activity were evaluated and compared with Fungizone® and pure AMB. Finally, in vivo safety evaluations were done. Results and discussion: Dendritic micelles inhibited AMB hemolysis and cytotoxicity in RAW 264.7 and HEK293 cell lines while increasing antifungal activity against C. albicans biofilm formation. Furthermore, significantly lower levels of liver and renal toxicity biomarkers compared to Fungizone® ensured AMB-incorporated dendritic micelle biosafety, which was confirmed by histopathological evaluations. Conclusion: All in all, the Chol-HPG and HPG@Chol dendritic micelles may be a viable alternative to commercially available AMB formulations as well as an effective delivery system for other poorly soluble antifungal agents.