Targeting Polymeric Nanoparticles to Specific Cell Populations in the Liver

Nanoparticles (NPs) are beneficial for delivery of drugs in a variety of settings, serving to protect their cargo and allow for sustained release. Polymeric NPs offer several advantages as therapeutics carriers due to their tunable characteristics like size and shape, ease of manufacturing, and biocompatibility. Despite this, there are no polymeric NPs that are approved for treatment of liver diseases. This is surprising since─when administered intravenously─the majority of NPs accumulate in cells in the liver. NP characteristics like size and surface charge can be altered to affect distribution to the liver, and even cellular distribution, but the conjugation of targeting ligands onto the NP surface for specific receptors on the cells is an important approach for enhancing cell specific delivery. Enhancing cell-specific targeting of conjugated NPs in the liver has two major hurdles: 1) avoiding accumulation of NPs in the liver resident macrophages known as Kupffer cells, which are optimized to phagocytose particulates, and 2) overcoming the transport barriers associated with architectural changes of the diseased liver. To identify the structures and mechanisms most important in NP design, NP administration during ex vivo perfusion (EVP)─achieved by anatomically isolating an organ by perfusing it outside the body─may be the most important and efficient approach. However, EVP is currently underutilized in the NP field, with limited research published on NPs delivered during liver EVP, and therefore representing an opportunity for future investigations.