Prospective therapeutics for intestinal and hepatic fibrosis

Currently, there are no effective therapies for intestinal and hepatic fibrosis representing a considerable unmet need. Breakthroughs in pathogenesis have accelerated the development of anti-fibrotic therapeutics in recent years. Particularly, with the development of nanotechnology, the harsh environment of the gastrointestinal tract and inaccessible microenvironment of fibrotic lesions seem to be no longer considered a great barrier to the use of anti-fibrotic drugs. In this review, we comprehensively summarize recent preclinical and clinical studies on intestinal and hepatic fibrosis. It is found that the targets for preclinical studies on intestinal fibrosis is varied, which could be divided into molecular, cellular, and tissues level, although little clinical trials are ongoing. Liver fibrosis clinical trials have focused on improving metabolic disorders, preventing the activation and proliferation of hepatic stellate cells, promoting the degradation of collagen, and reducing inflammation and cell death. At the preclinical stage, the therapeutic strategies have focused on drug targets and delivery systems. At last, promising remedies to the current challenges are based on multi-modal synergistic and targeted delivery therapies through mesenchymal stem cells, nanotechnology, and gut-liver axis providing useful insights into anti-fibrotic strategies for clinical use.