Abstract
Background: Silybin (Sb) is the major flavolignan of the extract of Silybum marianum. It is used for the treatment of various acute and chronic liver toxicities, inflammation, fibrosis and oxidative stress. Many studies indicate that Sb is also active against different carcinomas and it has been very recently proposed to be beneficial in type 2 diabetes patients. However, Sb is a low water soluble and low permeable compound.
Objective: In this study, Solid Lipid Nanoparticles (SLNs) were proposed to enhance the solubility and the intestinal absorption of Sb.
Methods: SLNs were made of stearic acid and Brij 78 and subsequently coated with chitosan. Formulations were physically and chemically characterized. Stability studies were also assessed. Sb in vitro release was evaluated in different pH media. In vitro permeability test with artificial membranes and Caco-2 cells were performed. Cellular uptake and mucoadhesion studies were conducted.
Results: Both nanoparticles were found to be stable. In vitro release indicated that SLNs may prevent burst release and gastric degradation of Sb. Higher extent of Sb permeation was observed for both nanoparticles in PAMPA and Caco-2 cell monolayer models. The results of the cellular uptake study suggested the involvement of active endocytic processes. Chitosan significantly improves mucoadhesion properties of nanoparticles.
Conclusions: Together with the excellent stability, strong mucoadhesive property, and slow release, chitosan coated SLNs demonstrated promising potential to enhance absorption of hydrophobic Sb after oral administration.
Keywords: Silybin (Sb), Solid lipid nanoparticles (SLNs), chitosan, in vitro permeation, Caco-2 up-take, PAMPA.
Graphical Abstract
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