Modification of taxifolin particles with an enteric coating material promotes repair of acute liver injury in mice through modulation of inflammation and autophagy signaling pathway

• Published in: Biomedicine & pharmacotherapy Vol. 152; p. 113242
• Main Authors: Ding, Qiteng, Chen, Kecheng, Liu, Xinglong, Ding, Chuanbo, Zhao, Yingchun, Sun, Shuwen, Zhang, Yiwen, Zhang, Jinping, Liu, Shuang, Liu, Wencong
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.08.2022; Elsevier
• Subjects: Acute liver injury; Autophagy; Hydroxypropyl methylcellulose acetate succinate; Inflammation; Taxifolin liposomes; Inflammation; Taxifolin liposomes; Acute liver injury; Autophagy; Hydroxypropyl methylcellulose acetate succinate
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.113242

Taxifolin (TAX) is a flavanol compound with hepatoprotective effect, but its application is severely limited by its poor water solubility and low oral bioavailability. Therefore, it is important to urgently find a method to improve the oral bioavailability of TAX. In this study, hydroxypropyl methylcellulose acetate succinate modified taxifolin liposomes (HPMCAS-TAX-Lips) were prepared by a thin-film dispersion method, and a series of physicochemical properties of the liposomes were studied. The cumulative in vitro release rates of free TAX, taxifolin liposomes (TAX-Lips), and HPMCAS-TAX-Lips in the simulated gastrointestinal fluid were measured by in vitro release experiments, and the effect of HPMCAS-TAX-Lips on the human hepatoellular carcinomas (HepG2) cells was detected by MTT assay. Finally, the hepatoprotective mechanism of HPMCAS-TAX-Lips was explored through in vivo experiments. The results showed that the particle size of HPMCAS-TAX-Lips was 100.44 ± 2.85 nm, the zeta potential was − 51.13 ± 0.57 mV, the PDI was 0.170 ± 0.088, and the EE was 87.9 ± 3.73%. The in vitro release results showed that the cumulative release rates of TAX-Lips and HPMCAS-TAX-Lips in simulated gastric fluid for 24 h were 92.60 ± 5.31% and 66.91 ± 1.20%, respectively. The cumulative release rates in simulated intestinal fluid for 24 h were 72.61 ± 4.38% and 53.94 ± 3.2%, respectively. The results of cytotoxicity experiments proved that HPMCAS-TAX-Lips had a significant inhibitory effect on HepG2 cells. In vivo experiments further showed that HPMCAS-TAX-Lips significantly improved the survival rate of lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury mice and exerted hepatoprotective effects by regulating the expression of autophagy proteins and inhibiting the activation of toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway. This study proved the significant hepatoprotective effect of HMPCAS-TAX-Lips and provided a new idea for the application of TAX. [Display omitted] •Modified taxifolin liposomes using enterosoluble coating material.•The mechanism of hepatoprotective effect of taxifolin was explored.•The hepatoprotective effect of taxifolin was improved.•Provided a new way for the development of new dosage forms of taxifolin.