In vitro and in situ profiling demonstrates BCS Class II properties for herpetrione in intestinal models, indicating that nanoparticles overcome solubility-limited absorption.
Key Points
Classify the biopharmaceutical properties of the hepatoprotective lignan herpetrione and develop a nanoparticle delivery system to overcome its low oral bioavailability.
Evaluated in silico properties and measured equilibrium solubility across gastrointestinal pH gradients.
Assessed bidirectional intestinal transport and efflux via Caco-2 cell monolayers, molecular docking with P-glycoprotein, and in situ single-pass intestinal perfusion (SPIP).
Fabricated and tested a nanoparticle drug delivery formulation to improve dissolution and solubility.
Herpetrione exhibited low, pH-dependent aqueous solubility, but jejunal effective permeability in SPIP exceeded the high-permeability benchmark, categorizing it as a BCS Class II agent.
Caco-2 transport demonstrated a high efflux ratio that aligned with molecular docking simulations, identifying herpetrione as a P-glycoprotein substrate.
Encapsulation into a nanoparticle formulation markedly improved both the aqueous solubility and dissolution rate of herpetrione.