| Abstrakt: |
Aim: The present study aims to develop, optimize and assess hispolon (HPN) lipid nanocapsules (LNCs), solid lipid nanoparticles (SLNs) and suspension for treating hepatocellular carcinoma (HCC). Materials & methods: It included UPLC-MS/MS, solubility, optimization, characterization, stability, in vitro and in vivo studies. Results: HPN-loaded LNCs were developed using phase-inversion and temperature cycling, while SLNs and suspension using hot homogenization and trituration methods. HPN-LNCs had a particle size (PS) of 196.9 nm, a PDI of 0.315 and a zeta potential of -24.3 mV. HPN-S2 had a PS of 199.90 nm, a PDI of 0.381 and a zeta potential of -19.1 mV. HPN-SPN3 showed a PS of 946.60 nm, a PDI of 0.31 and a zeta potential of -0.1945 mV. Stability tests over 3 months and gastric stability testing in different media showed no significant changes in PS, PDI, entrapment efficiency (EE) and loading capacity (LC). HPN-LNCs demonstrated 96.22% sustained drug release over 25 h, outperforming HPN-S2 (87.12%) and HPN-SPN3 (22% within 2 h). HPN-loaded LNCs improved oral bioavailability by 2.03-times, the most effective hepatoprotective action and higher localization in liver tumors over HPN-S2 and HPN-SPN3. Conclusion: HPN-Loaded LNCs results are promising, but more safety data needed in the future. Article highlights HCC is the sixth most common tumor globally. Key risk factors include hepatitis B and C infections, which account for 60–85% of cases worldwide, and exposure to aflatoxin B1. CLSPN (Claspin), a protein essential for normal DNA replication, is regulated by ubiquitination. Studies have shown that CLSPN plays a significant role in HCC. Elevated levels of CLSPN have been observed in HepG2 and Huh7 cell lines, commonly used in liver cancer research. The elevated levels of CLSPN in these cell lines suggest its potential as a biomarker for HCC. Understanding its molecular mechanisms, particularly its role in the Wnt/β-catenin pathway, could lead to new therapeutic targets. Hispolon (HPN), a phenolic compound from PL, has anti-inflammatory, antiproliferative and antimetastatic effects but faces biopharmaceutical challenges such as low solubility and rapid metabolism. HPN-loaded LNCs are developed using phase-inversion and temperature cycling. Solid lipid nanoparticles are developed using hot homogenization and suspension is developed through trituration. Stability over 3 months and gastric stability testing in different media showed no significant changes in PS, PDI, EE and LC of HPN-loaded LNCs, HPN-S2 and HPN-SPN3. HPN-loaded LNCs improved oral bioavailability by 2.03-times. HPN-loaded LNCs showed the most effective hepatoprotective action and higher localization in the liver tumor compared with HPN-S2 and HPN-SPN3 suspension. HPN-loaded LNCs show promise for HCC treatment, but more in vivo safety data is needed soon. [ABSTRACT FROM AUTHOR] |
