Chapter 15 - Drug Delivery and Medical Applications of Chemically Modified Hyaluronan

Abstract

Hyaluronan (HA) is a linear naturally occurring polyanionic polysaccharide that is ubiquitous in nature and is produced virtually by every tissue in higher organisms and some bacteria. HA has excellent biocompatibility and is readily catabolized and cleared in vivo. For these reasons, there has been a significant commercial focus on the development of products either from HA or from chemically modified derivatives of HA. HA and HA plus chemically cross-linked HA preparations are the principal components in several viscosupplements for patients with early-stage osteoarthritis of the knee. Conjugation of drugs to HA holds great promise for the generation of a new class of polymer-based therapeutics. These polymer-based systems can serve not only a biomaterials-based function, such as the separation or bulking of tissue, but also as concomitant drug delivery systems for the local delivery of therapeutics. Drugs conjugated to HA could also serve to target the drug to cells or tissues in the body that are rich in HA-binding receptors, such as CD44, RHAMM, TLR2, and TLR4. One of the most promising uses of chemically modified HA is in the area of tissue engineering. HA is found in the extracellular matrix of virtually all tissues so its use as a cell delivery vehicle is obvious. The combination of cell delivery and drug attachment to HA offers a very versatile material for the development of sophisticated products to address complex and unmet medical needs.