Iodine-containing cellulose mixed esters as radiopaque polymers for directembolization of cerebral aneurysms and arteriovenous malformations

The present study deals with the synthesis and characterization of radiopaq ue polymers which could, when solubilized in an appropriate water-miscible solvent, be useful embolic materials for the treatment of cerebral aneurysm s and arteriovenous malformations. For this purpose cellulose (both microcr ystalline and powdered) and partially substituted cellulose acetate (two di fferent viscosity grades) were selected as starting materials to prepare io dine-containing polymers through various synthetic routes. The materials ob tained were characterized by IR and NMR spectroscopy, molecular weight, iod ine content, radiopacity and solubility in selected injectable organic solv ents. The embolic liquids were evaluated for their precipitation behavior i n a phosphate buffer solution (pH 7.4) mimicking physiological conditions u sing an in vitro aneurysm model. A sheep model was also used to assess in v ivo the radiopacity and precipitation properties of a highly concentrated s olution of a cellulose acetate 2,3,4-triiodobenzoate mixed ester. AH materi als with 4-iodo- and 2,3,5-triiodobenzoyl groups gave sufficient radiopacit y to be regarded as possible embolization materials, whereas iododeoxycellu lose and iododeoxycellulose acetate were not radiopaque because of their lo w iodine content. Esters synthesized using cellulose as starting material w ere not soluble in the selected organic solvents due to the presence of man y residual hydroxyl groups, but could be used for other biomedical applicat ions where insoluble radiopaque materials are used. In contrast, solubility of the materials as well as satisfactory precipitation properties were ens ured using cellulose acetate as the starting material. In conclusion, cellu lose acetate iodobenzoate mixed esters dissolved in diglyme or dimethyl iso sorbide (dimethyl sulfoxide is probably less appropriate because of its tox icity and hemolytic properties) could be useful embolic liquids for the tre atment of cerebral aneurysms or arteriovenous malformations. (C) 2001 Elsev ier Science Ltd. All rights reserved.