Characterization and optimization of a zein-based mesoscopic complex system for Venenum Bufonis delivery

Venenum Bufonis (VB), a traditional Chinese medicine with multiple pharmacological activities, exhibits promising therapeutic potential but is limited by poor aqueous solubility, low bioavailability, and gastrointestinal irritation caused by its toxic components. Developing an effective delivery system is therefore critical for improving its application potential. In this study, zein was employed as a biocompatible carrier to encapsulate VB and construct zein-based mesoscopic complexes (MCS). Four zein-to-VB mass ratios were investigated, and the physicochemical properties, encapsulation performance, stability, and in vitro gastrointestinal release behaviors of the obtained complexes were systematically evaluated. Fourier transform infrared spectroscopy (FTIR) analysis suggested that hydrogen bonding and hydrophobic interactions contributed to the association between zein and VB. Among the investigated formulations, the zein-VB complex prepared at a zein-to-VB mass ratio of 10:1 exhibited the most favorable overall performance, with the highest encapsulation efficiency (98.29%) and moderate drug loading capacity (9.04%). Furthermore, this formulation demonstrated improved storage stability and sustained VB release behavior, with a cumulative release rate of 49.0% under simulated gastrointestinal conditions. The zein-based mesoscopic complex system effectively improved VB dispersibility and provided controlled release characteristics, which may reduce gastrointestinal irritation and enhance VB utilization efficiency. This study provides a potential strategy for developing plant protein-based delivery systems for VB and other poorly water-soluble bioactive compounds.