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

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).

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.

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 (P_eff ) for all nano-assemblies than the Pae solution, with GP-SAN exhibiting the highest ileal absorption, which may be attributed to preferential M-cell uptake facilitated by its protein-rich composition. Pharmacokinetic studies confirmed superior performance of GP-SAN with the highest AUC_0-t (11209.01 ± 2093.72 ng/mL·h) and C_max (2896.04 ± 255.01 ng/mL), representing 2.0-fold and 3.0-fold increases over Pae solution (5676.14 ± 311.61 ng/mL·h & 964.89 ± 128.81 ng/mL), respectively. GL-SNM and SGD-SAN also significantly enhanced the bioavailability (AUC_0-t increased by 65% and 45%, respectively).

These results suggested that nano-assemblies, particularly protein-based GP-SAN, provide a structural foundation for SGD's bioavailability-enhancing effect.