Comparative Evaluation of Nano-Assemblies From Shaoyao Gancao Decoction on Paeoniflorin Bioavailability.

Purpose: The present study aimed to systematically compare the in vitro and in vivo characteristics of three nano-assemblies with different components derived from Shaoyao Gancao Decoction (SGD), with particular emphasis on their differential effects on oral absorption of paeoniflorin (Pae). Methods: The self-assembled nanoparticles of SGD (SGD-SAN), glycyrrhizic acid self-assembled nanomicelles (GL-SNM), and Glycyrrhiza protein self-assembled nanoparticles (GP-SAN) were separated or prepared, and characterized in terms of particle size, zeta potential, morphology, drug loading, and in vitro release behavior. The single-pass intestinal perfusion and pharmacokinetic studies of SGD-SAN, GL-SNM, and GP-SAN following oral administration were performed to evaluate their absorption-enhancing effect. Chemical interference agents (NaCl, urea, and Tween 20) were added, followed by particle size detection, to identify the types of intermolecular forces in the self-assemblies. Results: Three nano-assemblies exhibited significant differences in particle size (133 nm for SGD-SAN, 154 nm for GL-SNM, and 184 nm for GP-SAN) and drug loading (5.54% for SGD-SAN, 10.70% for Pae GL-SNM, and 21.52% for Pae GP-SAN). While hydrophobic interactions act as the common core force driving the formation of all nano-assemblies, their dependencies on other intermolecular forces vary remarkably. SGD-SAN, GL-SNM, and GP-SAN exhibited sustained Pae release (50-75% over 12 h vs 100% for the Pae solution in 2 h). In situ intestinal perfusion in rats showed significantly higher effective permeability coefficients ( Conclusion: These results suggested that nano-assemblies, particularly protein-based GP-SAN, provide a structural foundation for SGD's bioavailability-enhancing effect.