Preparation and anti-hepatocellular carcinoma effect of nanostructured lipid carriers co-loaded with sorafenib and berberine

A synergistic nano-strategy co-delivering sorafenib and berberine to overcome resistance and reduce toxicity. • Optimized nanostructured lipid carriers with high drug loading, sustained release, and good stability were successfully prepared. • Pharmacokinetics showed significantly enhanced oral bioavailability (4.59-fold and 2.28-fold for SORB and BBR). • Superior antitumor efficacy and biosafety were systematically verified both in vitro and in vivo. Sorafenib (SORB) is a first-line drug for advanced hepatocellular carcinoma, but its clinical use is limited by poor water solubility, low oral bioavailability, and drug resistance. Berberine (BBR) has been shown to reverse multidrug resistance and enhance drug sensitivity. Here, we designed a nanostructured lipid carrier co-loaded with SORB and BBR (SBER NLC). The optimized formulation had a particle size of 123.17 ± 3.28 nm, PDI of 0.211 ± 0.012, and zeta potential of −18.30 ± 0.95 mV. Encapsulation efficiencies were 78.77 ± 0.93% (SORB) and 79.58 ± 1.04% (BBR), with drug loadings of 1.75 ± 0.06% and 1.28 ± 0.13%, respectively. SBER NLC showed stable storage properties and sustained release in simulated gastrointestinal fluids. Pharmacokinetic studies demonstrated significantly enhanced oral bioavailability of both drugs compared with free drug suspension. In vitro, SBER NLC exhibited stronger cytotoxicity and migration inhibition against HepG2 cells, while the blank carrier was nontoxic. In a HepG2 xenograft mouse model, SBER NLC achieved the strongest tumor suppression without causing body weight loss or major organ damage, and induced extensive nuclear pyknosis and necrosis in tumor tissue. This study provides an efficient nano-delivery strategy for combined SORB and BBR in hepatocellular carcinoma treatment. Download: Download high-res image (226KB) Download: Download full-size image