Click Chemistry with Polymers, Dendrimers, and Hydrogels for Drug Delivery


During the last decades, great efforts have been devoted to design polymers for reducing the toxicity, increasing the absorption, and improving the release profile of drugs. Advantage has been also taken from the inherent multivalency of polymers and dendrimers for the incorporation of diverse functional molecules of interest in targeting and diagnosis. In addition, polymeric hydrogels with the ability to encapsulate drugs and cells have been developed for drug delivery and tissue engineering applications. In the long road to this successful story, pharmaceutical sciences have been accompanied by parallel advances in synthetic methodologies allowing the preparation of precise polymeric materials with enhanced properties. In this context, the introduction of the click concept by Sharpless and coworkers in 2001 focusing the attention on modularity and orthogonality has greatly benefited polymer synthesis, an area where reaction efficiency and product purity are significantly challenged. The purpose of this Expert Review is to discuss the impact of click chemistry in the preparation and functionalization of polymers, dendrimers, and hydrogels of interest in drug delivery.

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atom transfer radical polymerization


2,2-bis(hydroxymethyl)propionic acid


bathophenanthroline disulphonated disodium salt


contrast agent




Concanavalin A




Cu(I)-catalyzed azide-alkyne cycloaddition




drug delivery system








enhanced permeability and retention


gallic acid-triethylene glycol


lower critical solution temperature


living radical polymerization


methacryloyloxyethyl phosphorylcholine


matrix metalloproteinase


magnetic resonance imaging


mesenchymal stem cells




poly(amido amine)


poly(ethylene glycol)


poly(ethylene imine)


poly(ethylene oxide)


polyion complex




propargyl methacrylate




poly(methyl methacrylate)




poly(oligo(ethylene glycol) acrylate)


poly(propylene imine)




poly(vinyl alcohol)


reversible addition-fragmentation chain transfer




ring-opening methathesis polymerization


reactive oxygen species


strain-promoted azide-alkyne cycloaddition


surface plasmon resonance




thiol-ene coupling






thiol-yne coupling


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Acknowledgments & DISCLOSURES

This work was financially supported by the Spanish Ministry of Science and Innovation (CTQ2009-10963 and CTQ2009-14146-C02-02) and the Xunta de Galicia (10CSA209021PR and CN2011/037).

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Correspondence to Eduardo Fernandez-Megia.

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Lallana, E., Fernandez-Trillo, F., Sousa-Herves, A. et al. Click Chemistry with Polymers, Dendrimers, and Hydrogels for Drug Delivery. Pharm Res 29, 902–921 (2012).

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Key Words

  • click chemistry
  • dendrimer
  • drug delivery
  • hydrogel
  • polymer