Superiority of amino-modified chiral mesoporous silica nanoparticles in delivering indometacin

Abstract

The present study established indometacin (IMC) delivery system with chiral mesoporous silica nanoparticles (CMSNs) and amino-modified chiral mesoporous silica nanoparticles (Amino-CMSNs) that previously reported as pharmaceutical excipients, and their systemic biological effects, mainly consisting of in vitro drug intestinal permeability, haemolysis assay, in vivo pharmacokinetics, anti-inflammation pharmacodynamics and gastric irritation, were addressed. It turned out that the two IMC delivery systems established by CMSN and Amino-CMSN significantly improved drug intestinal permeability due to the improved drug dissolution caused by conversion of drug crystalline state to amorphous phase. Further, IMC-loaded Amino-CMSN was the superior choice because of its higher dissolution rate. Furthermore, CMSN and Amino-CMSN were safe to be circulated in blood, and Amino-CMSN with significant lower haemolysis ratio than CMSN was better for the minimum haemolytic behaviour. Oral bioavailability and anti-inflammation effect of IMC delivery systems established by CMSN and Amino-CMSN were enhanced compared with IMC, which was attributed to the primary cause of the improvement of IMC dissolution, and Amino-CMSN exhibited better biological effect. As a result of these facts, it is believed that the effective delivery of IMC by Amino-CMSN will provide a new candidate to formulate poorly soluble drugs so as to significantly develop pharmaceutical application.