Evaluating The Therapeutic Efficacy Of Silymarin-Loaded Silica-Containing Redox Nanoparticles Against Liver Fibrosis In Mice

Abstract

Liver fibrosis is a chronic condition caused by the repetitive or prolonged liver injury that is currently has limited treatments. Silymarin, a hydrophobic drug, has demonstrated the potential anti-inflammatory and antioxidant properties, however, its poor solubility in aqueous solution and low bioavailability in the gastrointestinal (GI) tract limit its therapeutic effects. Henceforth, this thesis work aimed to employ the use of the silica-containing redox nanoparticles (siRNP) as nanocarriers to entrap silymarin and orally deliver to the liver site for fibrosis treatment. Via the mechanism of selfassembly of amphiphilic block copolymers, siRNP was prepared with two prominent characteristics. First, owning to its absorptive silica moieties that form the crosslinking structure in the core, siRNP was shown to be capable of providing the high and stable state of hydrophobic drug loading. Second, the nanoparticle backbone at the side chain of hydrophobic segment was designed with covalently conjugated nitroxide radicals that exposed great antioxidant properties. This designed siRNP therefore offering an useful drug delivery compound in harsh condition of GI tract. According to in vitro testing, SM@siRNP exerted an improving in the antioxidant and anti-inflammatory effects and as also the minimal toxicity against RAW 264.7 murine macrophage. The in vivo therapeutic effects investigation using a mice model of 4 weeks carbon tetrachloride (CCl4)-induced liver fibrosis in conjunction with orally treating with SM@siRNP at the dose of 20 mg/kg showed the reduction in the degree of inflammation in comparison to free silymarin. Ultimately, SM@siRNP was emphasized as a potential therapeutic compounds for liver fibrosis treatment.