The surface chemistry of a nanocellulose drug carrier unravelled by MAS-DNP†
Cellulose nanofibrils (CNF) are renewable bio-based materials with high specific area, which makes them ideal candidates for multiple emerging applications including for instance on-demand drug release. However, in-depth chemical and structural characterization of the CNF surface chemistry is still an open challenge, especially for low weight percentage of functionalization. This currently prevents the development of efficient, cost-effective and reproducible green synthetic routes and thus the widespread development of targeted and responsive drug-delivery CNF carriers. We show in this work how we use dynamic nuclear polarization (DNP) to overcome the sensitivity limitation of conventional solid-state NMR and gain insight into the surface chemistry of drug-functionalized TEMPO-oxidized cellulose nanofibrils. The DNP enhanced-NMR data can report unambiguously on the presence of trace amounts of TEMPO moieties and depolymerized cellulosic units in the starting material, as well as coupling agents on the CNFs surface (used in the heterogeneous reaction). This enables a precise estimation of the drug loading while differentiating adsorption from covalent bonding (∼1 wt% in our case) as opposed to other analytical techniques such as elemental analysis and conductometric titration that can neither detect the presence of coupling agents, nor differentiate unambiguously between adsorption and grafting. The approach, which does not rely on the use of 13C/15N enriched compounds, will be key to further develop efficient surface chemistry routes and has direct implication for the development of drug delivery applications both in terms of safety and dosage.