Elaboration of radiopaque iodinated nanoparticles for in situ control of local drug delivery

Drug delivery systems can benefit from intrinsic radiopacity as this property will allow following up the diffusion path of the nanoparticles containing the therapeutic drug after their local administration. Herein, we report the synthesis of iodinated derivatives of cellulose acetate (CA) and their formulation into aqueous radiopaque nanoparticle suspensions. Modification and purification of CA with mono- or tri-iodobenzoyl chloride were characterized by NMR spectroscopy and elemental analysis of iodine. In particular, measurements of diffusion coefficients by the DOSY 2D NMR method allowed controlling the complete elimination of non-grafted iodinated materials. Pure radiopaque CA was successfully achieved with an iodine content varying between 14 and 32%. Aqueous suspensions of nanoparticles were successfully formed, characterized by being spherical, <100 nm in size and stable as a suspension over 3 months. The degree of substitution, in particular the triiodo moieties, imparted a good level of radiopacity whether in dry powder form (2627 HU) or as a nanoparticle suspension (298 HU). These values are comparable to radiopacity of systems reported in literature to be in vivo visible. Loading of paclitaxel was successfully attempted, suggesting that the developed radiopaque nanoparticles can ultimately function as a drug delivery system. (C) 2009 Elsevier Ltd. All rights reserved.