Preparation and Characterization of Silymarin-Conjugated Gold Nanoparticles with Enhanced Anti-Fibrotic Therapeutic Effects against Hepatic Fibrosis in Rats: Role of MicroRNAs as Molecular Targets

Abdullah Saad Abdullah; Ibrahim El Tantawy El Sayed; Abdel Moneim A El-Torgoman; Noweir Ahmad Alghamdi; Sami Ullah; S Wageh; Maher A Kamel

doi:10.3390/biomedicines9121767

Preparation and Characterization of Silymarin-Conjugated Gold Nanoparticles with Enhanced Anti-Fibrotic Therapeutic Effects against Hepatic Fibrosis in Rats: Role of MicroRNAs as Molecular Targets

Biomedicines. 2021 Nov 25;9(12):1767. doi: 10.3390/biomedicines9121767.

Authors

Abdullah Saad Abdullah¹, Ibrahim El Tantawy El Sayed¹, Abdel Moneim A El-Torgoman¹, Noweir Ahmad Alghamdi², Sami Ullah^{3

4}, S Wageh^{5

6}, Maher A Kamel⁷

Affiliations

¹ Department of Chemistry, Faculty of Science, Menoufia University, Shebin El Koom 13829, Egypt.
² Department of Physics, Faculty of Science, Albaha University, Alaqiq 65779, Saudi Arabia.
³ Research Center for Advanced Materials Science (RCAMS), King Khalid University, P.O. Box 9004, Abha, 61413, Saudi Arabia.
⁴ Department of Chemistry, College of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia.
⁵ Department of Physics, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁶ Physics and Engineering Mathematics Department, Faculty of Electronic Engineering, Menoufia University, Menoufia 32952, Egypt.
⁷ Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria 21516, Egypt.

Abstract

Background: The main obstacles of silymarin (SIL) application in liver diseases are its low bioavailability, elevated metabolism, rapid excretion in bile and urine, and inefficient intestinal resorption. The study aimed to synthesize and characterize silymarin-conjugated gold nanoparticles (SGNPs) formulation to improve SIL bioavailability and release for potentiating its antifibrotic action.

Methods: Both SGNPs and gold nanoparticles (GNPs) were prepared and characterized using standard characterization techniques. The improved formulation was assessed for in vitro drug release study and in vivo study on rats using CCl₄ induced hepatic fibrosis model. SIL, SGNPs, and GNPs were administered by oral gavage daily for 30 days. At the end of the study, rats underwent anesthesia and were sacrificed, serum samples were collected for biochemical analysis. Liver tissues were collected to measure the genes and microRNAs (miRNAs) expressions. Also, histopathological and immunohistochemistry (IHC) examinations of hepatic tissues supported these results.

Results: The successful formation and conjugation of SGNPs were confirmed by measurements methods. The synthesized nanohybrid SGNPs showed significant antifibrotic therapeutic action against CCl₄-induced hepatic damage in rats, and preserved normal body weight, liver weight, liver index values, retained normal hepatic functions, lowered inflammatory markers, declined lipid peroxidation, and activated the antioxidant pathway nuclear factor erythroid-2-related factor 2 (NRF2). The antifibrotic activities of SGNPs mediated through enhancing the hepatic expression of the protective miRNAs; miR-22, miR-29c, and miR-219a which results in suppressed expression of the main fibrosis mediators; TGFβR1, COL3A1, and TGFβR2, respectively. The histopathology and IHC analysis confirmed the anti-fibrotic effects of SGNPs.

Conclusions: The successful synthesis of SGNPs with sizes ranging from 16 up to 20 nm and entrapment efficiency and loading capacity 96% and 38.69%, respectively. In vivo studies revealed that the obtained nano-formulation of SIL boosted its anti-fibrotic effects.

Keywords: epigenetics; gold nanoparticles; liver fibrosis; microRNAs; oxidative stress; silymarin.

Abstract

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