This technology presents novel liver-targeting glucocorticoid prodrugs designed to improve the treatment of inflammatory liver diseases and sepsis with enhanced efficacy and reduced systemic side effects.
Background: Inflammatory liver diseases and sepsis represent significant clinical challenges due to their complex immune responses and the difficulty in delivering effective treatments directly to the liver. Traditional glucocorticoids, such as dexamethasone and prednisolone, are widely used to reduce inflammation but suffer from limited liver specificity, resulting in undesirable side effects on other organs. To address these limitations, research efforts aimed to develop a drug delivery system that targets the liver more selectively, thereby maximizing therapeutic benefits while minimizing adverse effects elsewhere in the body. This need for liver-specific delivery motivated the invention of the described glucocorticoid prodrugs.
Technology Overview: The disclosed technology introduces novel liver-targeting prodrugs of dexamethasone, a potent glucocorticoid, by chemically conjugating it to cholic acid (a bile acid) via zwitterionic linkers. These modifications create highly hydrophilic dexamethasone prodrugs, designed to exploit the liver-specific bile acid transporter, Na+-taurocholate cotransporting polypeptide (NTCP), responsible for bile acid uptake in hepatocytes. By leveraging NTCP-mediated transport, these prodrugs achieve enhanced selective uptake into liver cells, thereby concentrating the anti-inflammatory action at the site of disease while reducing exposure and side effects in tissues outside of the liver. This targeted delivery mechanism results in improved regulation of inflammatory cytokines specifically within liver tissue, contributing to better therapeutic outcomes. Furthermore, these prodrugs exhibit significantly improved liver specificity and efficacy in comparison to conventional glucocorticoids. This innovation addresses the critical issue of systemic glucocorticoid toxicity by reducing off-target effects and supporting safer long-term treatment options for liver-related inflammatory conditions.
https://suny.technologypublisher.com/files/sites/adobestock_264616859.jpeg Picture for reference only, not a depiction of the invention
Advantages: • Enhanced Liver Targeting: Utilizes NTCP transporter for selective glucocorticoid delivery to liver cells, increasing treatment precision. • Reduced Side Effects: Minimizes exposure of glucocorticoids to non-liver tissues, lowering the risk of systemic adverse effects. • Improved Hydrophilicity: Chemical modification increases water solubility, facilitating efficient drug delivery and uptake. • Superior Anti-inflammatory Efficacy: Demonstrates more effective regulation of inflammatory cytokines in hepatic cells compared to standard treatments. • Potential for Broad Therapeutic Use: Suitable for various inflammatory liver diseases including alcoholic hepatitis, autoimmune hepatitis, and sepsis.
Applications: • Treatment of inflammatory liver diseases such as alcoholic hepatitis and autoimmune hepatitis. • Management of sepsis by targeting hepatic inflammation and regulating immune response. • Potential use in chronic liver inflammation conditions requiring targeted glucocorticoid therapy. • Research and development of next-generation liver-specific therapeutics with improved safety profiles.
Intellectual Property Summary: Patent application filed
Stage of Development: This technology is at an early development stage (TRL 3–4), with proof-of-concept demonstrated through the design and initial validation of liver-targeting glucocorticoid prodrugs; ongoing studies are focused on preclinical evaluation of efficacy, safety, and pharmacokinetics to enable further translational development.
Licensing Status: This technology is available for licensing.