Lipid-based nanoparticle technologies for liver targeting

Liver diseases such as hepatitis, cirrhosis, and hepatocellular carcinoma are global health problems accounting for approximately 800 million cases and over 2 million deaths per year worldwide. Major drawbacks of standard pharmacological therapies are the inability to deliver a sufficient concentration of a therapeutic agent to the diseased liver, and nonspecific drug delivery leading to undesirable systemic side effects. Additionally, depending on the specific liver disease, drug delivery to a subset of liver cells is required. In recent years, lipid nanoparticles have been developed to passively and actively target drugs to the liver. The success of this approach has been highlighted by the FDA-approval of the first liver-targeting lipid nanoparticle, ONPATTRO, in 2018 and many other promising candidate technologies are expected to follow. This review summarizes recent developments of various lipid-based liver-targeting technologies, namely solid-lipid nanoparticles, liposomes, niosomes and micelles, and discusses the challenges and future perspectives in this field.