Development of nanocarrier based thermosensitive mucoadhesive gel containing Metformin Hydrochloride and Silymarin for treatment of Oral Cancer

Abstract

Enhancement of in-vitro anti-oral cancer activities of silymarin using dispersion of nanostructured lipid carrier in mucoadhesive in-situ gel newlineThe bioactive herbal agent, silymarin (SME/SMR) proved to have an anticancer action against multiple actions by researchers. However, it shows poor solubility and bioavailability. To overcome these issues, SME-loaded NLCs were developed by melt emulsification method and optimized using 33 Box-Behnken design. The developed nanoformulation was spectroscopically characterized (SEM, ATR-FTIR, DSC, PXRD) and performed in-vitro release. Further, the formulation was dispersed in poloxamer/ carbopol gel and evaluated for gelling temperature, gelling time, viscosity, ex-vivo mucoadhesion, and ex-vivo permeation. The cytotoxic effect, cell cycle, and reactive oxygen species were evaluated for developed nanoformulation in gel dosage form compared with plain drug and nanoformulation against oral cancer KB cells. newlineThe developed nanoformulation demonstrated accepted physicochemical properties with sustained drug release. The nanoformulation-loaded gel dosage form showed suitable gel strength, gelling temperature, and viscosity for the oral cavity with a more sustained release drug. The developed gel dosage form showed greater cytotoxicity as compared with the plain drug and nanoformulation. Similarly, enhanced ROS generation potential and inducing apoptosis at the Sub-G0 phase support enhancing the effect of SME in nanocarrier in a gel dosage form.compared with plain drug and nanoformulation against oral cancer KB cells. newlineThe developed nanoformulation demonstrated accepted physicochemical properties with sustained drug release. The nanoformulation-loaded gel dosage form showed suitable gel strength, gelling temperature, and viscosity for the oral cavity with a more sustained release drug. The developed gel dosage form showed greater cytotoxicity as compared with the plain drug and nanoformulation.