Preparation and evaluation of modified lipid nanoparticles for targeting liver fibrosis

Abstract

Introduction: Development of an anti-fibrosis therapy system has become a research hotspot for scholars. Butein, displays anti-fibrotic effects through different pathways. However, therapy with herbal ingredients is hindered by impurities and low concentration in the target tissue. Hepatic stellate cells (HSCs), reservoirs of vitamin A (VA), are considered the main contributors to liver fibrogenesis. Targeted delivery using VA might lead to successful treatment.Purpose: The main goal of this study was evaluating the efficacy of butein on liver fibrosis amelioration using VA modified solid lipid nanoparticles (SLNs).Methods: Butein was synthesized using 2,4-dihydroxyacetophenone and 3,4-dihydroxybenzaldehyde. A novel VA-Myrj52 ester conjugate was also synthesized as a targeting agent. Products were purified using column chromatography. 1H nuclear magnetic resonance (NMR), 13C NMR, and Fourier-Transform Infrared Spectrometry (FT-IR) were implemented for structure confirmation.Next, butein was encapsulated inside the VA-modified SLNs (VA-SLNs) and formulations were optimized. Finally, the effect of the formulations was investigated in vitro and in vivo. To this end, biological activity of the liver and kidney was assessed. Liver and kidney tissues were also analyzed morphologically with hematoxylin and eosin (H&E) and Masson’s trichrome staining. Results: Prepared SLNs were negatively charged, they had a mean diameter of 150 nm and entrapment efficacy of 75 percent. 4 weeks of intraperitoneal injection of VA-SLNs in CCl4-induced fibrotic rats, reduced serum AST and ALT 58% and 72% respectively, concerning the CCl4 group. Additionally, after treatment histologic damage score declined and oxidative stress markers of liver/kidney tissue normalized.Conclusion: Recession of liver tissue damage supports the credibility of butein loaded modified SLNs as a drug-delivery system for treatment of liver fibrosis.