Development, Characterization, and Preclinical Evaluation of Curcumin-Loaded Solid Lipid Nanoparticles for Enhanced Antiviral Delivery Against Zika Virus Infection.

Abstract

The Zika virus (ZIKV), a neurotropic flavivirus, poses a significant global health threat due to its association with severe congenital malformations. The absence of approved antivirals necessitates novel therapeutic approaches. Curcumin, a natural polyphenol from Curcuma longa, exhibits potent anti-inflammatory and broad-spectrum antiviral properties but is plagued by poor solubility and bioavailability. This study aimed to develop and comprehensively evaluate 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, a high entrapment efficiency of 93.2%, and sustained in vitro release (52.89% over 24 hours). In Wistar rats, CUR-SLNs demonstrated a 15-fold increase in oral bioavailability compared to native curcumin and significant brain biodistribution. In a Vero cell-based antiviral assay, CUR-SLNs exhibited a 90% reduction in ZIKV plaque formation (IC50 = 2.5 µM), ten times more potent than native curcumin. Histopathological analysis in a lethal AG129 mouse model showed that CUR-SLN6 treatment provided marked protection against ZIKV-induced neuronal necrosis and inflammation, with efficacy comparable to Sofosbuvir. No systemic toxicity was observed. Stability studies confirmed the formulation's robustness. This study is the first to demonstrate that SLN-based delivery of curcumin not only enhances its bioavailability and brain targeting but also provides neuroprotective efficacy against ZIKV infection comparable to a direct-acting antiviral, highlighting its clinical potential as an oral neurotherapeutic agent.