Abstract
Polysaccharide conjugates are important renewable materials. If properly designed, they may for example be able to carry drugs, be proactive (e.g., with amino acid substituents) and can carry a charge. These aspects can be particularly useful for biomedical applications. Herein, we report a simple approach to preparing polysaccharide conjugates. Thiol-Michael additions can be mild, modular, and efficient, making them useful tools for post-modification and the tailoring of polysaccharide architecture. In this study, hydroxypropyl cellulose (HPC) and dextran (Dex) were modified by methacrylation. The resulting polysaccharide, bearing α,β-unsaturated esters with tunable DS (methacrylate), was reacted with various thiols, including 2-thioethylamine, cysteine, and thiol functional quaternary ammonium salt through thiol-Michael addition, affording functionalized conjugates. This click-like synthetic approach provided several advantages including a fast reaction rate, high conversion, and the use of water as a solvent. Among these polysaccharide conjugates, the ones bearing quaternary ammonium salts exhibited competitive antimicrobial performance, as supported by a minimum inhibitory concentration (MIC) study and tracked by SEM characterization. Overall, this methodology provides a versatile route to polysaccharide conjugates with diverse functionalities, enabling applications such as antimicrobial activity, gene or drug delivery, and biomimicry.
Highlights
Polysaccharide conjugates have proved to be valuable in drug delivery [1], gene delivery [2], as a vaccine carrier [3], and in many other biomedical applications
Dextran is so non-toxic that it is routinely used in intravenous infusions in the clinic, and is biodegraded in vivo and cleared through the kidneys once it reaches the appropriate DP, dextran derivatives have in vivo application potential; Dex-MA is soluble in several solvents, including DMSO, DMF, and water, providing a broad leeway for further chemical modification
We have demonstrated the concept of thiol-Michael addition to appended methacrylates as an efficient and versatile approach for preparing polysaccharide conjugates
Summary
Polysaccharide conjugates have proved to be valuable in drug delivery [1], gene delivery [2], as a vaccine carrier [3], and in many other biomedical applications. The development of new methods for functionalizing polysaccharides is an important task. “click chemistry” methods have been developed that share attractive features (e.g., rapid kinetics, mild conditions, high efficiency, high yield) and some have been applied to polysaccharides [4]. Thiol-Michael addition is mild, versatile and efficient, and is even more suitable for polysaccharide modification since it is tolerant to water and air. It is frequently used in the preparation of polysaccharide hydrogels, due to its typically rapid kinetics in water. Feijen [13] reported the modification of dextran with a vinyl sulfone, and used it as an acceptor for thiol-Michael addition to prepare degradable hydrogels.
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