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Pharmaceutical Research

, Volume 29, Issue 4, pp 902–921 | Cite as

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

  • Enrique Lallana
  • Francisco Fernandez-Trillo
  • Ana Sousa-Herves
  • Ricardo Riguera
  • Eduardo Fernandez-Megia
Expert Review

Abstract

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.

Key Words

click chemistry dendrimer drug delivery hydrogel polymer 

Abbreviations

AIBN

azobisisobutyronitrile

ATRP

atom transfer radical polymerization

bis-MPA

2,2-bis(hydroxymethyl)propionic acid

BPDS

bathophenanthroline disulphonated disodium salt

CA

contrast agent

CL

caprolactone

ConA

Concanavalin A

CPT

camptothecin

CuAAC

Cu(I)-catalyzed azide-alkyne cycloaddition

DBU

1,8-diazabicyclo[5.4.0]undec-7-ene

DDS

drug delivery system

DIPEA

N,N-diisopropylethylamine

DMPA

2,2-dimethoxy-2-phenylacetophenone

DOX

doxorubicin

EPR

enhanced permeability and retention

GATG

gallic acid-triethylene glycol

LCST

lower critical solution temperature

LRP

living radical polymerization

MAPC

methacryloyloxyethyl phosphorylcholine

MMP

matrix metalloproteinase

MRI

magnetic resonance imaging

MSC

mesenchymal stem cells

NMP

N-methyl-2-pyrrolidone

PAMAM

poly(amido amine)

PEG

poly(ethylene glycol)

PEI

poly(ethylene imine)

PEO

poly(ethylene oxide)

PIC

polyion complex

PLL

poly-L-lysine

PMA

propargyl methacrylate

PMDETA

N,N,N′,N′,N″-pentamethyldiethylenetriamine

PMMA

poly(methyl methacrylate)

PNIPAM

poly(N-isopropylacrylamide)

POEGA

poly(oligo(ethylene glycol) acrylate)

PPI

poly(propylene imine)

PS

poly(styrene)

PVA

poly(vinyl alcohol)

RAFT

reversible addition-fragmentation chain transfer

RGD

Arg-Gly-Asp

ROMP

ring-opening methathesis polymerization

ROS

reactive oxygen species

SPAAC

strain-promoted azide-alkyne cycloaddition

SPR

surface plasmon resonance

TBTA

tris(benzyltriazolylmethyl)amine

TEC

thiol-ene coupling

THPTA

tris(hydroxypropyltriazolylmethyl)amine

TMS

trimethylsilyl

TYC

thiol-yne coupling

Notes

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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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Enrique Lallana
    • 1
  • Francisco Fernandez-Trillo
    • 1
  • Ana Sousa-Herves
    • 1
  • Ricardo Riguera
    • 1
  • Eduardo Fernandez-Megia
    • 1
  1. 1.Department of Organic Chemistry Center for Research in Biological Chemistry & Molecular Materials (CIQUS)University of Santiago de CompostelaSantiago de CompostelaSpain

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