Xin Cheng
, Qin Lv, Shuang Tian
, Guiyan Jin, Wenbin Jin, Jiao Wang, Wenping Wang
*
Abstract
Purpose: Scutellarin (SCU) is a bioactive flavonoid whose therapeutic applications are limited by its poor aqueous solubility and low bioavailability. This study aimed to develop amorphous SCU nanoparticles stabilized with polyvinyl pyrrolidone K30 (PVP) via an anti-solvent precipitation method to enhance solubility, dissolution, and oral bioavailability.Methods: Amorphous SCU-PVP nanoparticles were prepared by ultrasonically dispersing SCU solution in dimethyl sulfoxide into dichloromethane containing PVP (solvent: anti-solvent ratio 1:40; SCU:PVP 1:1 w/w). The nanoparticles were characterized in terms of morphology (SEM), particle size (DLS), crystallinity (DSC, PXRD), drug-polymer interactions (FTIR), drug loading, solubility, and in vitro dissolution. Pharmacokinetics were evaluated in male Sprague-Dawley rats orally administered 100 mg/kg SCU as nanoparticles or bulk SCU. Plasma drug concentrations were quantified via HPLC, and parameters were analyzed using DAS 3.2.1. Results: The optimized nanoparticles exhibited an average size of 150 nm (pre-drying) and 800 nm (post-drying), with high drug loading (40%) and encapsulation efficiency (85%). FTIR and Hansen parameter calculations (Δδt= 8.18, Ra= 17.64) confirmed hydrogen bonding and miscibility between SCU and PVP. Amorphization (via DSC/PXRD) enhanced SCU solubility 5.8-fold in water. in vitro dissolution studies showed >80% SCU release within 5 min across all pH media (vs. <3% for bulk drug). Pharmacokinetic studies revealed 130% relative oral bioavailability and prolonged T1/2 for nanoparticles versus bulk SCU.Conclusion: PVP-stabilized amorphous nanoparticles significantly improve SCU’s solubility, dissolution rate, and oral bioavailability via hydrogen bonding and amorphization. This simple, scalable anti-solvent precipitation method offers a promising strategy for enhancing the delivery of poorly soluble flavonoids.