Hyaluronic Acid Bioconjugates for the Delivery of Bioactive Molecules

Hyaluronic acid (HA) has currently several therapeutic applications: in ophthalmology, osteoarthritis, wound healing, tissue regeneration, postoperative anti-adhesion and anesthetic medicine. In the last ten years, it has also been successfully investigated in the field of drug delivery, in the form of conjugates or hydrogel depot systems. HAylation, the covalent conjugation of HA to bioactive molecules, allows the overcoming of disadvantages associated with some pharmaceuticals, such as insolubility, instability and fast kidney clearance. These issues can be addressed also by covalent attachment of polyethylene glycol (PEGylation), but HA has the relevant advantages of biodegradability, high loading and specific targeting. In this review, the novel HA derivatives and the latest advances in HA-based drug delivery with a particular focus on the chemistry of conjugation will be discussed. Although, so far, there are no HA-drug conjugates on the market, several derivatives are presently under clinical investigation, and the promising results encourage further investigations and the exploitation of this versatile polysaccharide.