Lactobionic Acid Conjugated Quercetin Loaded Organically Modified Silica Nanoparticles Mitigates Cyclophosphamide...

The study was designed to investigate the therapeutic potential of lactobionic acid (LA) conjugated quercetin (Q) loaded organically modified silica nanoparticles (LA-Q-ORMOSIL) with bulk quercetin to mitigate cyclophosphamide (CP) induced liver injury.

Q-ORMOSIL nanoparticles were synthesized and characterized using UV-Vis spectroscopy, TEM, Zeta sizer, FTIR and EDX. Further, encapsulation efficiency and in vitro release kinetic study was done. Q-ORMOSIL nanoparticles surface were modified with lactobionic acid, a ligand for the asialoglycoprotein receptor on the hepatocyte surface. The hepatoprotective effects of Q-ORMOSIL and LA-Q-ORMOSIL nanoparticles were evaluated in vivo. Cyclophosphamide (20 mg/kg/day, i.p) was co-administered for seven days with bulk quercetin (50mg/kg/day) and quercetin nanoparticles (50µg/kg/day). After seven days, the number of biomarkers for liver function test and oxidative stress were determined in liver homogenate. Histopathological changes were also analyzed in control and treated liver tissues.

Physiochemical characterization of LA-Q-ORMOSIL nanoparticles depicts that the particles formed were of approx. 80 nm, spherical, monodispersed in nature and showed sustain drug release in in vitro study. Our results further suggested that Q-ORMOSIL and LA-Q-ORMOSIL nanoparticles significantly decreased tissue TBARS, ROS levels and ALT, AST, and ALP activities compared to CP induced group. On the other hand, tissue antioxidant levels (GSH, GST, and catalase) showed a significant increase in LA-Q-ORMOSIL treated group compared to the CP treated group confirming its high therapeutic efficacy during liver injury.

Targeted nanoquercetin demonstrated a significant hepatoprotective effect compared to bulk quercetin against CP-induced hepatotoxicity and it considerably reduced bulk quercetin dose level to many folds. Bulk quercetin has low bioavailability and thus, from obtained data we suggest that LA-Q-ORMOSIL nanoparticles provide high therapeutic value in protecting experimental animals against CP-induced liver injury. We also propose multifunctional dye-doped LA-modified ORMOSIL nanoparticles for future studies in facilitating nanoparticles uptake to hepatocytes for liver diagnosis and treatment.