
Mingxing WEI
Lyon University.
France
Abstract Title: Nanoparticles Targeting LSEC Improve Liver-Specific Statin Delivery
Biography:
Dr. Wei pursued further training at Harvard Medical School. Alongside numerous scientific publications, he secured research grants. In 2001, Dr. Wei founded Cellvax for more than two decades. Cellvax has garnered an outstanding reputation as a service company, specializing in cancer and osteoarthritis animal models, alongside conducting GLP toxicity and PK/Biodistribution studies. Additionally, the company has played a pivotal role in large collaborative programs funded by the European Commission, further enriching its research and bolstering its prominence. Cellvax also maintains a strong partnership with Montpellier University Hospital in France, focusing on stem cell technology.
Research Interest:
This study was funded through the European collaborative project EuroNanoMed III. We developed functionalized polymeric micelles (FPMs) loaded with simvastatin (FPM-Sim) as a drug delivery system aimed at targeting liver sinusoidal endothelial cells (LSECs) to preserve liver function in chronic liver disease (CLD). Polymeric micelles (PMs) underwent functionalization by coupling peptide ligands of LSEC membrane receptors CD32b, CD36, and ITGB3. Confirmation of functionalization was achieved through spectroscopy and electron microscopy. In vitro and in vivo internalization of FPM-Sim was assessed using flow cytometry in LSECs, hepatocytes, Kupffer cells, and hepatic stellate cells from healthy rats. Maximum tolerated dose (MTD) assays were conducted in healthy mice, and efficacy studies of FPM-Sim were performed in bile duct ligation (BDL) and thioacetamide (TAA) induction rat models of cirrhosis. Functionalization with the three peptide ligands yielded stable formulations with increased in vivo internalization in LSECs compared to nonfunctionalized PMs. Administration of FPM-Sim in BDL rats mitigated toxicity relative to free simvastatin, albeit with a moderate portal-pressure-lowering effect. In a less severe model of TAA-induced cirrhosis, treatment with FPM-CD32b-Sim nanoparticles for two weeks significantly reduced portal pressure, correlated with decreased liver fibrosis, reduced collagen expression, and enhanced nitric oxide synthesis. In conclusion, CD32b-FPM emerges as a promising nanotransporter for drug delivery, effectively targeting LSECs, pivotal players in liver injury