Molecular mechanisms of conjugated zinc nano-particles for nano drug delivery against hepatic cirrhosis in CCl4-induced rats model

Abstract

The study aimed to develop and analyze a conjugated zinc Nano particle formulation that would enhance its anti-cirrhosis activity by increasing its bioavailability and release. Standard characterization procedures were used to create and analyze zinc nano particles (ZNPs). Drug release and hepatic cirrhosis model testing were conducted on rats utilizing the enhanced formulation. For 30 days, ZnNPs were supplied through oral gavage. For biochemical examination of serum samples, rats were anesthetized and slaughtered after the research. The expression of genes and microRNAs (miRNAs) in liver tissues was studied; together with expression of liver specific genes and inflammatory markers. These findings were also validated by liver tissue histological and immune histochemical (IHC) studies. Measuring techniques demonstrated the practical synthesis and conjugation of ZnNPs. Nanohybrid ZnNPs showed significant anticirrhosis therapeutic activity. ZnNPs' anti-cirrhosis properties decrease TGFR1 and COL3A1 expression, because they enhance the production of miRNAs that protect against cirrhosis. Furthermore, the expression of cancer markers (AFP, p53) was down/up-regulated in ZnNPs treated groups. Similarly, the pro- and anti-inflammatory markers expressions were found normalized in ZnNPs groups compared to untreated groups. These results were further validated by histopathology and IHC analysis, which showed that ZnNPs have anti-fibrotic properties. We finally, conclude that the that we achieve loading capacity of 94%, 36.63%, respectively, in the successful synthesis of ZnNPs. Furthermore, ZnNPs exhibits in vivo hepato-protective activity by down-regulating hepatic cancer markers and upregulating hepatic functional markers which assure the use of ZnNPs for the treatment of liver cirrhosis in future studies.