Nanostructured lipid nanoparticles delivering berberine with Se coating: a new nanotherapeutic approach against cryptosporidiosis

Berberine (BBR) exhibits broad antimicrobial and metabolic activities but suffers from limited bioavailability. Nanostructured lipid carriers (NLCs) can enhance oral delivery, while selenium (Se) coating may synergistically improve hypoglycemic and antiparasitic effects. This study aimed to design and evaluate the selenium-doped, berberine-loaded nanostructured lipid carriers (BBR-SeNLCs) for enhanced absorption, tissue diffusion, and antiparasitic efficacy against <i>Cryptosporidium parvum</i> in an immunosuppressed mouse model. BBR-SeNLCs were prepared <i>via</i> hot-melt dispersion/homogenization, followed by <i>in situ</i> reduction to deposit elemental selenium on the nanoparticle surface. A <i>Cryptosporidium</i> murine infection model was established. Parasitological burden (oocyst shedding), biochemical markers (ALT and AST), immunological parameters (IFN-γ, TNF-α, IL-6, and IL-10), and TEM ultrastructure of intestinal tissues were assessed. BBR-SeNLCs demonstrated successful berberine encapsulation. Among treatments, BBR-SeNLCs achieved comparable antiparasitic effects, with a notable reduction in oocyst shedding relative to infected controls. Biochemical assays indicate formulation-dependent hepatoprotective trends, particularly in BBR-SeNLCs formulations. Immunologically, Se-containing groups (Se alone and BBR-SeNLCs) displayed a shift toward moderated inflammatory responses (reduced IFN-γ, TNF-α, IL-6) with preserved or enhanced anti-inflammatory IL-10, suggesting balanced host immunity. Parasitological and ultrastructural analyses corroborated these findings, with BBR-SeNLCs showing preserved intestinal architecture and reduced parasite burden in treated groups.