From the brain to the liver: A pharmacokinetic dilemma and safety barriers in levodopa-based antifibrotic therapy

Figure 2 Future translational strategies toward precision antifibrotic therapy. The schematic summarizes three complementary domains. Precision therapeutics include hepatic stellate cell (HSC)-targeted delivery systems, such as nanoparticle-based levodopa prodrugs, and the development of peripherally restricted or highly selective dopamine receptor D1 modulators to minimize off-target receptor activation. Comprehensive evaluation emphasizes spatial multi-omics mapping of dopamine receptor D1 and dopamine receptor D2 expression across stages of liver disease, together with systematic assessment of portal hemodynamics and liver regeneration. Clinical goals focus on achieving effective antifibrotic efficacy through HSC inactivation while preserving hepatocyte regenerative capacity and ensuring yes-associated protein signaling safety, alongside maintenance of stable portal hemodynamics. HSC: Hepatic stellate cell; DRD: Dopamine receptor D; YAP: Yes-associated protein.