Current research on hyaluronic acid-drug bioconjugates.

Hyaluronic acid (HA) is a mucopolysaccharide acid composed of repeating disaccharide units of D-glucuronic acid and N-acetyl-D-glucosamine. Based on numerous characteristics such as viscoelastic properties, water-binding ability, biocompatibility and non-immunogenicity, HA has been approved by FDA for biological and medical applications. In addition, multifarious receptors of HA like CD44, RHAMM and TSG6 are over-expressed on the surface of malignant cells, which play important roles in targeting ability. Bioconjugates linking drugs to HA could improve solubility, prolong half-life, provide active targeting capability and then increase the bioavailability of these coupled drugs by pro-drug strategy. Therefore, a large number of HA-drug bioconjugates have been studied. The purpose of this review was to summarize these HA-drug bioconjugates and further discuss synthetic methods and the relevant application in pharmaceuticals.