Nanostructured hyaluronic acid-based materials for active delivery to cancer.

IMPORTANCE OF THE FIELD: Active targeting of bioactive molecules by physicochemical association with hyaluronic acid (HA) is an attractive approach in current nanomedicine because HA is biocompatible, non-toxic and non-inflammatory. AREAS COVERED IN THIS REVIEW: This review focuses on synthesis, physicochemical characterization and biological properties of different nanoparticulate delivery systems that include HA in their structures. Chemically based approaches to the delivery of small molecule drugs, proteins and nucleic acids in which they become chemically or physically bound to hyaluronic acid are reviewed, including the use of molecular HA conjugates and nanocarriers. The systems are considered in terms of intracellular delivery to different cultured cells that express HA-specific receptors (hyaladherines) differently. The in vivo biodistribution and therapeutic effect of these systems are discussed. WHAT THE READER WILL GAIN: Different synthetic methodologies for preparations of HA-based nanoparticles are presented extensively. HA nanoparticulate systems of various structures can be compared with respect to their in vitro assays and in vivo biodistribution. TAKE HOME MESSAGE: To make HA useful as an intravenous targeting carrier, strategies have to be devised to: reduce HA clearance from the blood; suppress the HA uptake by liver and spleen; and provide tumor-triggered mechanisms of release of an active drug from the HA carrier.