Liver-Targeted Delivery Based on Prodrug: Passive and Active Approaches.

BACKGROUND: The liver, a central organ in human metabolism, is often the primary target for drugs. However, conditions such as viral hepatitis, cirrhosis, non-alcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC) present substantial health challenges worldwide. Existing treatments, which suffer from the non-specific distribution of drugs, frequently fail to achieve desired efficacy and safety, risking unnecessary liver harm and systemic side effects. PURPOSE: The aim of this review is to synthesize the latest progress in the design of liver-targeted prodrugs, with a focus on passive and active targeting strategies, providing new insights into the development of liver-targeted therapeutic approaches. METHODS: This study conducted an extensive literature search through databases like Google Scholar, PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI), systematically collecting and selecting recent research on liver-targeted prodrugs. The focus was on targeting mechanisms, including the Enhanced Permeability and Retention (EPR) effect, the unique microenvironment of liver cancer, and active targeting through specific transporters and receptors. RESULTS: Active targeting strategies achieve precise drug delivery by binding specific ligands to liver surface receptors. Passive targeting takes advantage of the EPR effect and tumor characteristics to enrich drugs in liver tumors. The review details successful cases of using small molecule ligands, peptides, antibodies and nanoparticles as drug carriers. CONCLUSION: Liver-targeted prodrug strategies show great potential in enhancing the efficacy of drug treatment and reducing side effects for liver diseases. Future research should balance the advantages and limitations of both targeting strategies, focusing on optimizing drug design and targeting efficiency, especially for clinical application. In-depth research on liver-specific receptors and the development of innovative targeting molecules are crucial for advancing the field of liver-targeted prodrugs.

Progress in phosphorylation of natural products.

Natural medicines are a valuable resource for the development of new drugs. However, factors such as low solubility and poor bioavailability of certain constituents have hindered their efficacy and potential as pharmaceuticals. Structural modification of natural products has emerged as an important research area for drug development. Phosphorylation groups, as crucial endogenous active groups, have been extensively utilized for structural modification and development of new drugs based on natural molecules. Incorporating phosphate groups into natural molecules not only enhances their stability, bioavailability, and pharmacological properties, but also improves their biological activity by altering their charge, hydrogen bonding, and spatial structure. This review summarizes the phosphorylation mechanism, modification approaches, and biological activity enhancement of natural medicines. Notably, compounds such as polysaccharides, flavonoids, terpenoids, anthraquinones, and coumarins exhibit increased antioxidation, anticancer, antiviral, immune regulatory, Antiaging, enzyme inhibition, bacteriostasis, liver protection, and lipid-lowering effects following phosphorylation modification.