Preparation and Evaluation of Plumbagin-Loaded Lipid Cubic Liquid Crystal Nano-drug Delivery System

To address the poor water solubility and low oral absorption of plumbagin (PL), an anti-hepatocellular carcinoma (HCC) agent, we developed lipidic cubic liquid crystalline nanoparticles (LCNPs) as an oral delivery system to enhance its druggability. PL-loaded LCNPs（PL-LCNPs）were prepared by the ethanol injection method, and optimized via single-factor tests combined with Box-Behnken response surface methodology (BBD-RSM). In vitro release was evaluated by dynamic dialysis, while in vivo fate was assessed by small animal imaging and rat pharmacokinetics. The optimized PL-LCNPs exhibited a particle size of (203.50 ± 2.05) nm, zeta potential of (-39.51 ± 0.95) mV, Encapsulation Efficiency (EE) of (80.21 ± 0.95)%, and Drug Loading (DL) of (5.66 ± 0.98)%. In simulated gastrointestinal fluid, the cumulative release of PL-LCNPs reached 92% at 10 h, significantly higher than 48% of free PL, and the release fitted the Weibull equation. The relative oral bioavailability of PL-LCNPs was 295.58% relative to free PL. This study provides a feasible strategy for poorly soluble traditional Chinese medicine oral preparations, and PL-LCNPs show promising clinical potential as a high-efficiency, low-toxicity oral chemotherapy for HCC.