Hyaluronan-carbon nanotube derivatives: Synthesis, conjugation with model drugs, and DOSY NMR characterization

Carbon nanotube (CNTs) derivatives are nowadays under thorough investigation as biomedically interesting materials. In this paper we describe a method for the preparation of water-soluble CNTs by condensation of the carboxylic groups introduced onto the carbon framework and the primary amine moieties inserted in the naturally occurring biopolymer hyaluronan (HA). The covalent conjugation between CNTs and HA should merge the biocompatibility and further processability of the HA chains with the well-known cellular penetration properties of the CNT derivatives to produce novel drug delivery platforms. In fact, thanks to the primary amino groups introduced in the HA chains, HA-CNT derivatives can be further covalently modified with model drugs like ibuprofen and methotrexate. We describe also the monitoring of all the CNT derivatization steps by diffusion-ordered NMR spectroscopy (DOSY), a technique that allows fast and reliable characterization of these novel derivatives.