Background
Orally administered sorafenib has shown limited improvement in overall survival for non-small-cell lung cancer patients, likely due to poor pharmacokinetics and adverse effects, including gastrointestinal toxicity. To address these issues, we developed silica-containing antioxidant nanoparticles (siRNP) as a carrier to enhance the therapeutic efficacy of lipophilic sorafenib.
Conclusions
These findings demonstrate that nanosilica-crosslinked antioxidant nanoparticles (siRNP) enhance the stability, delivery efficiency, and safety of lipophilic drugs like sorafenib for oral administration. This platform holds promise for improving therapeutic outcomes in lung cancer while minimizing adverse effects.
Methods
Sorafenib was loaded into siRNP via dialysis (sora@siRNP). The therapeutic efficacy and safety of sora@siRNP (20 and 40 mg-sora/kg) were evaluated in a xenograft mouse model of Lewis lung carcinoma (subcutaneous tumors and experimental metastasis) following oral administration.
Results
Crosslinking nanosilica in siRNP improved drug stability, enabling 8.9% sorafenib loading and pH resilience. Oral sora@siRNP exhibited dose-dependent tumor growth suppression by downregulating pMEK, outperforming free sorafenib, which showed inconsistent efficacy likely due to formulation variability. Intestinal damage, a major adverse effect of free sorafenib, was significantly reduced with sora@siRNP, attributed to siRNP's antioxidant property of mitigating oxidative damage. Survival rates in the experimental metastasis model were 66-74% for sorafenib but reached 100% for sora@siRNP, highlighting its superior efficacy and safety. Conclusions: These findings demonstrate that nanosilica-crosslinked antioxidant nanoparticles (siRNP) enhance the stability, delivery efficiency, and safety of lipophilic drugs like sorafenib for oral administration. This platform holds promise for improving therapeutic outcomes in lung cancer while minimizing adverse effects.