Abstract
Liver fibrosis currently represents a global health problem without effective pharmacotherapeutic strategies. The clinical translation of polydatin, a promising natural anti‐fibrotic drug candidate with broad anti‐inflammatory and antioxidant capabilities, remains a major challenge due to its limited water solubility and tissue absorption. Herein, a polydatin‐loaded micelle (PD‐MC) based on reactive oxygen species (ROS) and pH dual‐sensitive block polymer PEG‐P(PBEM‐co‐DPA) is developed. The micelle exerts great potential in improving the biocompatibility of polydatin and shows highly efficient liver‐targeted drug release in response to the fibrotic microenvironment. Both in vitro and in vivo studies demonstrate that PD‐MC can significantly suppress inflammatory response and oxidative stress, reduce hepatocyte apoptosis, and avert activation of macrophages and hepatic stellate cells. More excitingly, the blank micelle itself promotes the hepatic ROS consumption at the pathologic site to provide anti‐inflammatory benefits. These favorable therapeutic virtues of targeting multiple cell types endow PD‐MC with remarkable efficacy with minimal side effects in liver fibrosis treatment. Thus, PD‐MC holds great potential to push forward the clinical application of polydatin in pharmacotherapeutic approaches against liver fibrosis.
Highlights
Liver fibrosis currently represents a global health problem without effective which represent the leading causes of liver-related mortality worldwide.[3]
Advanced liver fibrosis usually quiescent hepatic stellate cells (HSCs) to differentiate into activated myofibroblasts, progresses into irreversible cirrhosis and portal hypertension, i.e., the principle extracellular matrix (ECM)-synthesizing cells which act as the key
A polydatin-encapsulated micelle (PD-MC) with reactive oxygen species (ROS) and pH dual-sensitivity is developed based on block polymer PEG-bP(PBEM-co-DPA) for the liver fibrosis therapy
Summary
Liver fibrosis currently represents a global health problem without effective which represent the leading causes of liver-related mortality worldwide.[3]. The micelle exerts great potential in Hepatic fibrogenesis is a complex improving the biocompatibility of polydatin and shows highly efficient livermulti-cellular pathophysiological process targeted drug release in response to the fibrotic microenvironment. Both in vitro and in vivo studies demonstrate that PD-MC can significantly suppress inflammatory response and oxidative stress, reduce hepatocyte apoptosis, and avert activation of macrophages and hepatic stellate cells. The involving the mutual interaction between parenchymal hepatocytes and nonparenchymal liver cells including hepatic stellate cells (HSCs), Kupffer cells (KCs) and liver sinusoidal endothelial cells (LSECs).[5] Despite different etiologies such as site to provide anti-inflammatory benefits. A reversible wound healing response that follows of the inflammatory response in liver fibrosis via releasing vast chronic hepatic injury, is characterized by excess accumulation proinflammatory and oxidation-related mediators that irritate of extracellular matrix (ECM).[1,2] Advanced liver fibrosis usually quiescent HSCs to differentiate into activated myofibroblasts, progresses into irreversible cirrhosis and portal hypertension, i.e., the principle ECM-synthesizing cells which act as the key
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