Oral VA-SNEDDS delivers morin to hepatic stellate cells, significantly attenuating liver fibrosis in rats.

Chronic hepatic fibrosis is a progressive liver disease marked by excessive extracellular matrix (ECM) accumulation, primarily driven by activated hepatic stellate cells (aHSCs). Current treatments often fall short, and long-term management requires non-invasive strategies. Oral medication is ideal for prolonged therapy, yet achieving targeted drug delivery to aHSCs via oral routes remains a significant challenge due to the vulnerability of nanoparticles to degradation during intestinal transit. This study addresses this critical gap by developing a robust oral delivery system.

Researchers fabricated an oral vitamin A (VA)-functionalized self-nanoemulsifying drug delivery system, termed VA-SNEDDS, designed for precise delivery of morin (MOR) to aHSCs. The system's integrity and translocation were assessed after oral administration. Its therapeutic efficacy was then evaluated in a carbon tetrachloride (CCl4)-induced fibrotic rat model. Primary endpoints included measuring ECM deposition, hydroxyproline content, and transforming growth factor-β1 (TGF-β1) expression, alongside assessing overall liver function. The study aimed to demonstrate successful intestinal translocation, systemic circulation via the lymphatic pathway, and targeted accumulation in aHSCs.

The designed VA-SNEDDS successfully translocated across the intestinal epithelium, maintaining its structural integrity, and entered systemic circulation via the lymphatic pathway. Crucially, it ultimately accumulated in aHSCs within fibrotic livers through VA- and retinol-binding protein receptor-mediated binding. This targeted delivery mechanism proved effective in vivo. In the CCl4-induced fibrotic rat model, treatment with MOR-loaded VA-SNEDDS significantly attenuated liver fibrosis. This attenuation was evidenced by a reduction in ECM deposition, hydroxyproline content, and transforming growth factor-β1 (TGF-β1) expression. Concurrently, the treatment restored liver function, indicating a broad therapeutic benefit. While specific quantitative data (e.g., percentages, p-values) were not detailed in the abstract, the findings consistently pointed to a robust anti-fibrotic effect.

The oral MOR-loaded VA-SNEDDS significantly attenuated liver fibrosis by reducing ECM deposition, hydroxyproline content, and TGF-β1 expression, while restoring liver function.