Preclinical study demonstrates 97% lesion size reduction in Leishmania major-infected mice, indicating dendrimer-based nano-fluconazole enhances cutaneous leishmaniasis therapy.
Cutaneous leishmaniasis (CL) remains a therapeutic challenge due to drug resistance and the toxicity of conventional treatments. This study developed a dendrimer-based nanostructure conjugating fluconazole with chitosan to enhance therapeutic efficacy. We employed Nuclear Magnetic Resonance (NMR) - based metabolomics to elucidate the underlying mechanism of action. The dendrimer-chitosan-fluconazole nanostructure was characterized using Dynamic Light Scattering (DLS) , Scanning Electron Microscopy (SEM) , and Fourier-Transform Infrared (FTIR) spectroscopy. We evaluated drug loading, release kinetics, and in vitro/in vivo efficacy against Leishmania major . Safety was assessed through cytotoxicity, hematological, biochemical, and histopathological analyses. The nanostructure exhibited uniform morphology with drug-loading efficiencies of 49% (chitosan) and 56% (fluconazole), enabling enhanced solubility and sustained release. The formulation (NFLZ/Chi) displayed potent in vitro activity (IC₅₀ = 13 µg/mL; CI = 0.61) and a 97% reduction in lesion size in a murine model. Metabolomic profiling revealed significant disruptions in amino acid, carbohydrate, and lipid pathways—specifically branched-chain amino acid and glycine/serine/threonine metabolism. Toxicity assays indicated favorable preliminary biocompatibility. This dendrimer-based system shows promising potential for CL management. Metabolomic insights suggest treatment-associated metabolic alterations, warranting further investigation into their biological significance and clinical potential.
No takes yet. Share an insight, caveat, or question.
Fadaei et al. (2026) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: