COVID-19 mRNA vaccine (Tonix)

Solid lipid nanoparticles (SLNs) have garnered significant interest for their safety and efficacy, especially following the success of COVID-19 mRNA vaccines. This study presents the synthesis and characterization of a novel stearic acid (SA)-gambogic acid (GA) conjugate, where GA, a xanthonoid, exhibits high affinity for the transferrin receptor (TfR) without competing with endogenous transferrin. The SA-GA conjugate was employed to formulate SLNs using a hot homogenization-ultrasonication-solvent evaporation technique for the peroral delivery of cyclosporine (CsA), paclitaxel (PTX), and urolithin-A (UA). Physicochemical properties, including particle size, zeta potential, drug loading, and entrapment efficiency, were assessed. Among the three tested compounds, UA exhibited the highest encapsulation efficiency at both 5% and 10% w/w loading, with particle sizes remaining under 250 nm. SA-GA SLNs demonstrated excellent stability in simulated gastric fluids, supporting their potential for oral administration. Cellular uptake studies using Coumarin-6 (C6) and drug-loaded SLNs indicated that UA achieved the highest uptake (~ 50%) in both FHS-74 (human small intestine) and HK2 (human kidney) cell lines. Further, in cisplatin-induced HK2 cell damage models, UA-loaded SA-GA SLNs significantly reduced inflammatory markers TLR4, NF-κB, and IL-1β. These results highlight UA-loaded SA-GA SLNs as a promising TfR-targeted oral delivery system for mitigating cisplatin-induced acute kidney injury (AKI) in cancer therapy.