The aim of the NANOSIM project, an international and interdisciplinary initiative led by the Vall d'Hebron Research Institute (VHIR), is to achieve a method of drug delivery using nanoparticles to improve the efficacy and increase the safety of treatments for chronic liver disease. Until now, the only therapeutic option for patients has been limited to eliminating the aetiological agent (or external promoter of damage), either a virus, such as Hepatitis B, or a substance, such as alcohol. Once the agent is eliminated, only preventive treatment of the main associated complications is possible, but nothing to prevent or delay liver damage. Now, the team behind NANOSIM has published a study in the journal Pharmaceutics that opens the door to a treatment that specifically targets the liver's sinusoidal endothelial cells, which are the primary inducers of liver damage. The innovation is not a new medicine, but a new delivery method that uses nanotechnology to allow the drug to act directly on key liver cells.

NANOSIM is a European-funded project coordinated by Dr. María Martell, head of the Advanced Chronic Liver Diseases laboratory within the Liver Diseases group at VHIR and with the collaboration of Dr. Ibane Abasolo, head of the Clinical Biochemistry, Drug Delivery and Therapy group at VHIR. The researchers of both groups belong to the Centro de Investigación Biomédica en Red (CIBER) in the area of Liver and Digestive Diseases (CiberEHD) and Biomedicine, Biomaterial and Nanomedicine (CiberBBN), respectively. The U20 of the unique scientific infrastructure (ICTS) Nanbiosis has also participated in the study. Dr Martell stresses the importance of developing new and better treatments for cirrhosis: "Chronic liver diseases are the fifth leading cause of death in adults aged 50-70 and account for 85% of liver transplants. In Europe alone, an estimated 29 million people are affected".
 

A new delivery method for an old drug

The research team focused on simvastatin, a drug used as an adjunct therapy for cholesterol that had been shown to have a protective role for endothelial cells, which are essential in preventing the creation of liver fibrosis that causes liver inflammation. The problem is that oral or intravenous administration of the required dose causes a number of side effects, both muscular and hepatic, which limits its use. The aim of the research was to find a way to deliver the drug directly to the endothelial cells of the hepatic sinusoid without it spreading to other parts of the body and causing unwanted side effects.

This active and specific targeting was achieved by binding polymeric micelles to peptides recognised by the liver endothelial cell-specific surface marker CD32b. In this way, a reduction in liver fibrosis was observed in in-vivo models without a significant increase in toxicity and, therefore, an effective and safe method to treat chronic liver diseases. 

Dr. Abasolo adds "that once we have demonstrated the efficacy of the technology to directly reach the endothelial cells of the sinusoids, it opens up a wide range of possible medicaments with which we can use this nanotechnology to improve liver function".

*Institutional Statement on the use of experimental animals.