Synthesis and preparation of vitamin A coupled butein-loaded solid lipid nanoparticles for liver fibrosis therapy in rats.

[Display omitted] • Vitamin A-Myrj52 easter conjugate could be used as a liver targeting ligand. • Vitamin A coupled SLNs were prepared to target liver fibrosis in rats. • Vitamin A coupled butein loaded SLNs normalize liver function markers and oxidative stress markers after 4 weeks of treatment. • Butein decreases kidney injury and reduces serum urea and creatinine levels. The development of a therapeutic system for hepatic fibrosis has become a research hotspot to date. Butein, a simple chalcone derivative, displays anti-fibrotic effects through different pathways. However, impurities, low solubility, and low concentration in the target tissue hinder therapy with herbal ingredients. Hepatic stellate cells (HSCs), the vitamin A (VA) storage cells, as the main contributors to liver fibrogenesis, are not readily accessible to drugs owing to their anatomical location. Targeted delivery of therapeutics to the activated HSCs is therefore critical for successful treatment. For these reasons, the current study aimed at increasing butein delivery to the liver. Hence, high purity butein was synthesized in three steps. A novel VA-Myrj52 ester conjugate was also synthesized using all-trans retinoic acid and a hydrophilic emulsifier (Myrj52) as a targeting agent. Next, butein was encapsulated inside the novel VA-modified solid lipid nanoparticles (VA-SLNs) and studied in vitro and in vivo. According to our evaluations, negatively charged SLNs with a mean diameter of 150 nm and entrapment efficacy of 75 % were successful in liver fibrosis amelioration. Intraperitoneal (i.p.) injection of VA-SLNs in fibrotic rats, for four weeks long, reduced serum AST and ALT by 58% (P, 0.001) and 72% (P, 0.05), respectively, concerning the CCl 4 group. Additionally, histologic damage score decline and normalization of tissue oxidative stress markers collectively confirmed the efficacy of formulations in hepatic fibrosis and kidney damage amelioration. [ABSTRACT FROM AUTHOR]