In vitro release and in vitro–in vivo correlation for silybin meglumine incorporated into hollow-type mesoporous silica nanoparticles

Abstract

Xia Cao*, Wen-Wen Deng*, Min Fu*, Liang Wang, Shan-Shan Tong, Ya-Wei Wei, Ying Xu, Wei-Yan Su, Xi-Ming Xu, Jiang-Nan YuDepartment of Pharmaceutics, School of Pharmacy, and Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang, People’s Republic of China *These authors contributed equally to this workBackground: The purpose of this study was to develop a sustained drug-release model for water-soluble drugs using silica nanoparticles.Methods: Hollow-type mesoporous silica nanoparticles (HMSNs) were prepared using Na2CO3 solution as the dissolution medium for the first time. The water-soluble compound, silybin meglumine, was used as the model drug. The Wagner-Nelson method was used to calculate the in vivo absorption fraction.Results: The results of transmission electron microscopy and nitrogen adsorption revealed that the empty HMSNs had uniformly distributed particles of size 50–100 nm, a spherical appearance, a large specific surface area (385.89 ± 1.12 m2/g), and ultralow mean pore size (2.74 nm). The highly porous structure allowed a large drug-loading rate (58.91% ± 0.39%). In 0.08 M Na2CO3 solution, silybin meglumine-loaded HMSNs could achieve highly efficacious and long-term sustained release for 72 hours in vitro. The results of in vitro–in vivo correlation revealed that HMSNs in 0.08 M Na2CO3 solution had a correlation coefficient R2 value of 0.9931, while those of artificial gastric juice and artificial intestinal juice were only 0.9287 and 0.7689, respectively.Conclusion: The findings of in vitro–in vivo correlation indicate that HMSNs together with Na2CO3 solution could achieve an excellent linear relationship between in vitro dissolution and in vivo absorption for 72 hours, leading to a promising model for sustained release of water-soluble drugs.Keywords: hollow-type mesoporous silica nanoparticle, silybin meglumine, in vitro dissolution, in vivo absorption, in vitro–in vivo correlation