Two-step immobilization of metronidazole prodrug on TEMPO cellulose nanofibrils through thiol-yne click chemistry for in situ controlled release.

Nowadays, drug encapsulation and drug release from cellulose nanofibrils systems are intense research topics, and commercial grades of cellulose nanomaterials are currently available. In this work we present an ester-containing prodrug of metronidazole that is covalently bound to cellulose nanofibrils in aqueous suspension through a two-step immobilization procedure involving green chemistry principles. The presence of the drug is confirmed by several characterization tools and methods such as Raman spectroscopy, elemental analysis, Dynamic Nuclear Polarization enhanced NMR. This technique allows enhancing the sensitivity of NMR by several orders of magnitude. It has been used to study cellulose nanofibrils substrates and it appears as the ultimate tool to confirm the covalent nature of the binding through thiol-yne click chemistry. Moreover, the ester function of the immobilized prodrug can be cleaved by specific enzyme activity thus allowing controlled drug release.

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.

Biohybrid cellulose fibers: Toward paper materials with wet strength properties.

Herein, we report on the preparation of novel cellulose-PEG biohybrid papers with wet strength properties. The biohybrid paper sheets are obtained using a two-step procedure where ω- or α, ω-azide functionalized PEG chains are anchored onto alkyne-functionalized wood fibers through CuAAC ligation in mild and aqueous conditions. The incorporation of the PEG grafts mostly occurs at the periphery of the cellulose fibers and degrees of substitution up to 0.028 are obtained. The presence of PEG grafts significantly increases the tensile, burst and tear strength properties in the wet state, the reinforcement being more pronounced for fibers grafted with α,ω-azide PEG. This reinforcement is consistent with a relatively sparse hetero-crosslink reaction creating inter-fiber covalent bonds and forming a cellulose network within the cell wall.

Green nondegrading approach to alkyne-functionalized cellulose fibers and biohybrids thereof: synthesis and mapping of the derivatization.

Alkyne-functionalized cellulose fibers have been generated through etherification under basic water or hydroalcoholic conditions (NaOH/H(2)O/isopropanol). For a given NaOH content, the medium of reaction and, more particularly, the water/IPA ratio, were shown to be of crucial importance to derivatize the fibers without altering their integrity and their crystalline nature. It was shown that the degree of substitution (DS) of the fibers increases concomitantly with isopropanol weight ratio and that, contrary to water or water-rich conditions, derivatization of fibers under isopropanol-rich conditions induces an alteration of the fibers. Optimization of etherification conditions in aqueous media afforded functionalized cellulose materials with DS up to 0.20. Raman confocal microscopy on derivatized fibers cross sections stressed that alkyne moieties are incorporated all over the fibers. The resulting fibers were postfunctionalized by molecular probes and macromolecules in aqueous or water-rich conditions. The effectiveness of the grafting was strongly impacted by the nature of the coupling agents.

Interactions between poly(ethylene oxide) and fatty acids sodium salts studied by surface tension measurements.

This work focuses onto the interactions between poly(ethylene oxide) (PEO) and fatty acids, in order to set their potential role of contaminants for PEO-based retention systems. Surface tension measurements were used to investigate PEO-fatty acid systems and they made it possible to clearly point out the interactions between the polymer and the sodium octadecylcarboxylates with different degrees of unsaturation. The observed interaction seems to be dependent on the fatty acids' solubility, the increase of which leads to less pronounced phenomena, which are, in contrast, emphasized by the increase in PEO chain length.