Potential of Silymarin and Metformin Co-Loaded Nanostructured Lipid Carriers Containing Mucoadhesive Thermogel on KB Cells of Oral Cancer

The current work aimed to prepare silymarin (SMR) and metformin (MTH)-loaded nanostructured lipid carriers (NLCs) added in-situ thermoresponsive gel for the treatment of oral cancer. In brief, the nanostructured lipid carriers were designed using Compritol and oleic acid whereas the mucoadhesive sol-gel thermoresponsive system was prepared using gellan gum/Poloxamer. The obtained SMR/MTH-NLCs were characterized for Fourier transform infrared spectroscopy–attenuated total reflectance, scanning electron microscope (SEM), transmission electron microscope (TEM), atomic force microscopy (AFM), particle size, zeta potential, in-vitro release, etc. Moreover, the SMR/MTH-NLCs incorporated gel was characterized for sol-gel temperature, viscosity, ex-vivo mucoadhesion, etc. Here, SMR/MTH-NLCs showed a spherical shape with a particle size of 258.2 ± 1.2 nm and zeta potential − 35 ± 0.2 mV, respectively. Further, the sol-gel transition could form gel at 35.2 ± 0.5 ℃ providing site-specific and sustained release of SMR and MTH. Ex-vivo permeation of formulation exhibited longer retention that confirmed the good mucoadhesion potential of gellan gum. The cell viability studies demonstrated a significant reduction of KB oral cancer cells that confirms the increased synergistic anticancer effects of SMR/MTH-NLCs incorporated gel (IC₅₀ = 0.65 ± 0.12 µM) than free drug combination. These findings illicit the potential of SMR/MTH-NLCs incorporated gel formulation to localize delivery of SMR and MTH at buccal mucosa in the treatment of oral cancer.

Graphical Abstract