Carbohydrate Polymers 85 (2011) 469–489 Contents lists available at ScienceDirect Carbohydrate Polymers journal homepage: www.elsevier.com/locate/carbpol Review Chemical modifications of hyaluronic acid for the synthesis of derivatives for a broad range of biomedical applications Carole E. Schanté a,b,* , Guy Zuber a , Corinne Herlin b , Thierry F. Vandamme a a Laboratoire de Conception et Application de Molécules Bioactives, Université de Strasbourg UMR7199, Faculté de Pharmacie, 74 route du Rhin, 67400 Illkirch, France b Laboratoire IDENOV, 8 rue de Reims, 67000 Strasbourg, France article info Article history: Received 21 December 2010 Received in revised form 1 March 2011 Accepted 11 March 2011 Available online 21 March 2011 Keywords: Hyaluronic acid derivative Chemical modification Crosslinking Conjugation Drug delivery Characterization abstract Hyaluronic acid (HA) is widely used for numerous medical applications, such as viscosupplementation, eye surgery and drug delivery. A broad range of HA-based materials have been developed and described for the enhancement, modulation and control of its therapeutic action, based on chemical modification of polysaccharides. The purpose of this paper is to review the various chemical modification methods and synthetic routes to obtain HA derivatives, encompassing all applications. © 2011 Elsevier Ltd. All rights reserved. Contents 1. Introduction .......................................................................................................................................... 470 2. Hyaluronic acid, its physicochemical properties, biosynthesis, degradation and applications ..................................................... 470 2.1. Chemical structure and physicochemical properties ........................................................................................ 470 2.2. HA occurrence in the organism and physiological functions ................................................................................ 471 2.3. Degradation of HA ............................................................................................................................ 471 2.4. Therapeutic uses .............................................................................................................................. 471 2.5. Extraction or synthesis of HA ................................................................................................................ 471 3. Various chemical methods used for the synthesis of HA derivatives ............................................................................... 471 3.1. Modification of the –COOH ................................................................................................................... 472 3.1.1. Amidation ........................................................................................................................... 472 3.1.2. Ugi condensation ................................................................................................................... 475 3.1.3. Ester formation ..................................................................................................................... 475 3.2. Modifications of the –OH ..................................................................................................................... 477 3.2.1. Ether formation ..................................................................................................................... 477 3.2.2. Hemiacetal formation using glutaraldehyde ....................................................................................... 477 3.2.3. Ester formation ..................................................................................................................... 477 3.2.4. Carbamate formation ............................................................................................................... 478 3.2.5. Oxidization with sodium periodate ................................................................................................ 478 3.3. Modification of the –NHCOCH 3 .............................................................................................................. 479 * Corresponding author at: Laboratoire de Conception et Application de Molécules Bioactives, Université de Strasbourg UMR7199, Faculté de Pharmacie, 74 route du Rhin, 67400 Illkirch, France. Tel.: +33 3 68 85 41 06. E-mail address: carole.schante@etu.unistra.fr (C.E. Schanté). 0144-8617/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.carbpol.2011.03.019