Chiral microenvironment-responsive mesoporous silica nanoparticles for delivering indometacin with chiral recognition function

Abstract

The purpose of this study was to investigate the potential chiral recognition functions induced by two kinds of novel chiral microenvironment-responsive mesoporous silica nanoparticles (CMR-L-MSN and CMR-D-MSN) for the oral delivery of the poorly water-soluble achiral drug indomethacin (IMC). The as-synthesized CMR-L-MSN and CMR-D-MSN with molecular chirality and high specific surface area (SBET: 1141 and 1075 m2/g, respectively) were successfully prepared through grafting chiral molecular functional groups. The characterization results showed that CMR-L-MSN and CMR-D-MSN were spherical nanoparticles with opposite chiral features and clearly visible pore channels. Meanwhile, they exhibited good biosafety and degradability. In vitro drug release study indicated that both CMR-L-MSN and CMR-D-MSN significantly improved IMC dissolution compared with naked-MSN (N-MSN) (p < 0.05) and exhibited different chiral recognition functions for drug release in the simulated chiral environments in vitro (pH 6.8 PBS-D/L), in which CMR-D-MSN could be triggered by the L-configurations in chiral environments and exhibited a better drug release effect. As expect, the results of in vivo biological effects disclosed that CMR-D-MSN had higher bioavailability of IMC and obvious advantages on drug adsorption and in vivo distribution, and exerted stronger anti-inflammatory effect after making specific response to the in vivo chiral environment.

Keywords

• Chiral microenvironment-response
• High specific surface area
• Chiral recognition
• Biological effects
• Indometacin