RESUMEN
The incidence of acetaminophen-induced liver injury has increased, but effective prevention methods are limited. Although luteolin has hepatoprotective activity, its low solubility and bioavailability limit its applications. Cyclodextrin metal-organic frameworks (CD-MOFs) possess 3D-network structures and large inner cavities, which make them excellent carriers of poorly soluble drugs. In this study, we used CD-MOFs as carriers to improve the dissolution of luteolin and assessed their antioxidant activity, bioavailability, and hepatoprotective effects. Luteolin was loaded into ß-CD-MOF, γ-CD-MOF, ß-CD, and γ-CD, and characterized by powder X-ray diffractometry (PXRD) and thermogravimetric analysis (TGA). Our results showed that luteolin-ß-CD-MOF was the most stable. The main driving forces were hydrogen bonds and van der Waals forces, as determined by molecular simulation. The loading capacity of luteolin-ß-CD-MOF was 14.67 wt%. Compared to raw luteolin, luteolin-ß-CD-MOF exhibited a 4.50-fold increase in dissolution and increased antioxidant activity in vitro. Luteolin-ß-CD-MOF increased the bioavailability of luteolin by approximately 4.04- and 11.07-fold in healthy rats and liver injured rats induced by acetaminophen in vivo, respectively. As determined by biochemical analysis, luteolin-ß-CD-MOF exhibited a better hepatoprotective effect than raw luteolin in rats with acetaminophen-induced liver injury. This study provides a new approach for preventing acetaminophen-mediated liver damage.
RESUMEN
Polymer micelles now have promising applications in the treatment of cancer, increasing the water solubility and bioavailability of drugs. Previous studies have found that micelles of niclosamide have good anti-liver cancer effect. In view of the poor water solubility of niclosamide (NIC), we decided to prepare niclosamide micelles. However, its therapeutic mechanism is not clear, so this paper conducted a preliminary study on its vitro anti-tumour mechanism and metabonomics to find out its impact. It was found that the drug-loaded micelles (PEG2K -FIbu/NIC) had an inhibitory effect on HepG2 cells. Moreover, it can promote apoptosis of HepG2 cells and block S and G2/M phase of cell cycle. The plasma and liver metabolomics of mice in normal group, model group and administration group were studied by UPLC-MS and 1 H-NMR. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to process the data and find the relevant metabolites. metaboanalyst 5.0 was used to integrate the relevant metabolites to find the main related metabolic pathways. Thus, the anti-tumour mechanism of PEG2K -FIbu/NIC was analysed. Fifty-one biomarkers were detected in plasma, and 43 biomarkers were detected in liver. After comprehensive biomarker and metabolic pathway analysis, it was found that PEG2K -FIbu/NIC micelles could affect the changes of many metabolites, mainly affecting amino acid metabolism. This article is an in-depth study based on the published Preparation and pharmacodynamics of niclosamide micelles (DOI: 10.1016/j.jddst.2021.103088).