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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Ossipov
Dmitri A
DA
Uppsala University, Polymer Chemistry, Material Chemistry Department, S-75121 Uppsala, Sweden. dmitri.ossipov@mkem.uu.se
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D049329:Nanostructures; D009369:Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D004337:Drug Carriers; D006820:Hyaluronic Acid