Alanine modified chiral-responsive mesoporous silica as nanocarriers for improved oral bioavailability of carvedilol

Abstract

Alanine-modified chiral mesoporous silica (CMS) was firstly synthesized using chiral silane coupling agent (L-Ala-ICPTES or D-Ala-ICPTES) deriving from L-alanine or D-alanine, which was denoted as L-Ala-MSN and D-Ala-MSN, respectively. The as-prepared CMSs exhibited highly ordered mesoporous structure with spherical morphology, huge specific surface area and pore volume, successful modification of alanine and opposite chirality, which was identified by transmission electron microscope (TEM), small angle X-ray diffraction (SAXRD), nitrogen adsorption/desorption measurement, fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and induced circular dichroism (ICD). We also found that the biocompatibility of alanine modified CMSs was better than that of unmodified CMSs, which was confirmed by wettability test, degradation analysis, hemolysis test, protein adsorption test and evaluation of gastrointestinal irritation. Above all, the CMSs exerted chiral-selective delivery of achiral drug carvedilol (CAR) in simulated chiral environments. Pharmacokinetic studies revealed that L-Ala-MSN and D-Ala-MSN could significantly improve oral bioavailability of carvedilol (168.43% and 230.18% respectively), and D-Ala-MSN could delivery more drugs in vivo . This work has laid a theoretical foundation for rational design of chiral nano-drug delivery systems and promoted the application and development of CMSs in medicine. • CMSs were firstly obtained by chiral silane coupling agent deriving from L/D-alanine. • CMSs exhibited good biocompatibility and chiral-selective delivery of carvedilol. • CMSs had significantly improved the oral bioavailability of carvedilol.