(532a) Photocured Hyaluronic Acid Films Functionalized with Cyclodextrin

We are developing a hyaluronic acid-β-cyclodextrin hydrogel film for drug delivery. Hyaluronic acid is a naturally occurring biopolymer that is notable for its excellent biocompatibility and enzymatic biodegradability. It has been adapted for several biomedical products including intra-articular injections for lubricating arthritic joints, subdermal injections for filling soft tissue defects, and films for preventing intra-peritoneal adhesions. We are using a photoreactive methacryloyl-hyaluronic acid (MHA) derivative as the base material for a biodegradable drug-releasing film. To produce these films aqueous MHA solutions with photoinitiator were cast and dried under sterile conditions. The dry MHA films were equilibrated under controlled relative humidity and crosslinked by solvent-free photocuring. After rehydration the films exhibited low swelling and relatively small changes in dimension. Hydrogels, such as hyaluronic acid gels, are generally biocompatible, resemble native tissues and are attractive materials for some drug delivery applications; however, many drugs are poorly water-soluble and not ideally suited for delivery by water swollen hydrogels. Cyclodextrin is a cyclic glucose oligomer that greatly increases drug solubility by guest-host complexation. We believe that functionalization of hyaluronic acid hydrogels with cyclodextrin groups will confer on the hydrogels the property of guest-host complexation and permit them to be loaded with greater amounts of poorly water-soluble drugs. We have synthesized and characterized a methacryloyl-β-cyclodextrin monomer for this purpose. Our synthesis of methacryloyl-β-cyclodextrin is a single step reaction performed in aqueous media that uses only parent β-cyclodextrin and methacrylic anhydride as reactants and sodium hydroxide as base catalyst. The purified product is a mixture of cyclodextrins bearing between 1 and 6 methacrylic functional groups and no detectable unreacted cyclodextrin. The methacryloyl-β-cyclodextrin was considerably more soluble than the underivatized cyclodextrin and retained the property of inclusion complexation with a model drug, hydrocortisone. We are currently using this monomer to functionalize MHA hydrogels to produce drug releasing hyaluronic acid-β-cyclodextrin hydrogel films.