Development, characterisation and preclinical evaluation of curcumin-loaded solid lipid nanoparticles for enhanced...

The Zika virus (ZIKV), a neurotropic flavivirus, poses a global health threat with no approved antivirals. Curcumin, a natural polyphenol, exhibits potent antiviral properties but suffers from poor bioavailability. This study developed Curcumin-loaded Solid Lipid Nanoparticles (CUR-SLNs) to overcome these limitations. A 3² factorial design optimized SLNs using glyceryl monostearate. The lead formulation (CUR-SLN6) exhibited a particle size of 53.25 nm, high entrapment efficiency (93.2%), and sustained release (52.89% over 24 h). In Wistar rats, CUR-SLNs demonstrated a 15-fold increase in oral bioavailability and significant brain biodistribution. In Vero cells, CUR-SLNs exhibited 90% reduction in ZIKV plaque formation (IC₅₀ = 2.5 µM), ten times more potent than native curcumin. Mechanistic studies revealed inhibition of viral entry and a 3-log reduction in viral RNA replication. Histopathological analysis in a lethal AG129 mouse model showed CUR-SLN6 provided marked neuroprotection against ZIKV-induced necrosis and inflammation, with efficacy comparable to Sofosbuvir. No systemic toxicity was observed. The method demonstrated excellent greenness (AGREE score 0.86) and whiteness (RGB score 90). This first demonstration of SLN-based curcumin delivery with enhanced bioavailability, brain targeting, and neuroprotective efficacy highlights its clinical potential as an oral neurotherapeutic agent.