Mannose-engineered nanoparticles for site-specific delivery of fluconazole to treat cutaneous leishmaniasis

Background Cutaneous leishmaniasis (CL) is a skin disease that affects people living in arid and semi-arid regions. The main limitation in current management is that treatment primarily targets the cutaneous lesions, while immune-mediated effects is often not addressed. In addition, there is a need for new treatment with minimized side effects. Fluconazole (FCZ) has been used for treating CL before. Methods In the present study, FCZ was entrapped in a chitosan (CS) nanopolymer and conjugated with mannose (MNS) to target amastigotes inside macrophages in CL-infected Balb/c male mice. Parasites were detected using Enzyme-Linked Immunosorbent Assay (ELISA) and Polymerase chain reaction (PCR). Results The resulting FCZ CS MNS NPs nanoparticles exhibited small size (71.96 ± 11.4 nm) good stability (31.2 ± 0.173 nm), release over an extended period, and long-term bioavailability. The FCZ CS MNS nanoparticle-treated mice showed negative PCR results and low IgG levels compared to the positive control ( P < 0.0001). This indicated potent targeting of infected macrophages that affects the parasite before it replicates and exits into the bloodstream. This study provides evidence for the effect of an antileishmanial formulation. Additional toxicity studies should be performed on this formulation before it undergoes clinical trials.