PH-responsive release of anesthetic lidocaine derivative QX-OH from mesoporous silica nanoparticles mediated by ester bonds

Abstract

The quaternary lidocaine derivative QX-OH is a promising candidate for efficient local anesthesia, but sufficient membrane permeability and pharmacokinetic controllability are still required for clinical usage. In this study, we demonstrated ester-based pH-cleavable loading of QX-OH onto carboxyl-functionalized mesoporous silica nanoparticles (MSN) to control pH-responsive release. MSN was prepared by a sol-gel method, and the surface was functionalized with an amine group and then with a carboxyl group. The properties of the MSNs were characterized by scanning electron microscopy, Fourier-transformed infrared spectroscopy (FT-IR), thermogravimetry–differential thermal analysis, Brunauer–Emmett–Teller method, and zeta potential measurement. A sufficient amount of QX-OH, 24.5 wt%, was loaded into the carboxyl-functionalized MSN (MSN_QX-OH) by ester binding. The FT-IR spectrum of MSN_QX-OH showed that the peak of the carboxyl group shifted to a higher wavenumber, that is, QX-OH was bound to the surface via ester bond. MSN_QX-OH released 26% QX-OH at physiological pH for 8 h. Furthermore, when the pH of the solvent was lowered to 5.5, mimicking the endosomal condition, acid hydrolysis of the ester bond released 66% QX-OH within 1 h. In conclusion, the introduction of an ester bond between QX-OH and MSN would efficiently provide a local anesthetic via pH-responsive release.