Polymer-Based Therapeutics - PubMed (original) (raw)

Polymer-Based Therapeutics

Shuang Liu et al. Macromolecules. 2009.

Abstract

Polymeric materials have been applied in therapeutic applications, such as drug delivery and tissue regeneration, for decades owing to their biocompatibility and suitable mechanical properties. In addition, select polymer-drug conjugates have been used as bioactive pharmaceuticals owing to their increased drug efficacy, solubility, and target specificity compared with small-molecule drugs. Increased synthetic control of polymer properties has permitted the production of polymer assemblies for the targeted and controlled delivery of drugs, and polymeric sequestrants take advantage of their lack of solubility for the sequestration of target molecules in vivo. In more recent studies reviewed in greater detail here, the properties of polymers that distinguish them from small-molecule drugs, such as their high molecular weight and their ability to display multiple pendant moieties, have been specifically exploited for activating cellular targets or inhibiting the binding of pathogens. The elucidation of relevant structure-function relationships in investigations of this kind has relied on the combination of living polymerization methods with chemical conjugation methods, and protein engineering methods have shown increasing potential in the manipulation of architectural features of such polymer therapeutics. Garnering a detailed understanding of the various mechanisms by which multivalent polymers engage biological targets is certain to expand the role of polymers as therapeutics, by enabling highly specific activities of designed polymers in the biological environment.

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Figures

Figure 1

Figure 1

Schematics of polymeric delivery vehicles: (A) polymer matrix; (B) polymer assembly; (C) polymer complex.

Figure 2

Figure 2

Schematic illustrating polymer sequestrants.

Figure 3

Figure 3

Schematics illustrating temperature-, pH-, and enzyme-sensitive drug delivery systems.

Figure 4

Figure 4

Release of small-molecule drugs from polymerized drugs via backbone hydrolysis.

Figure 5

Figure 5

Schematics of interaction between ligands and receptors: (A) interaction between monovalent ligands and receptor; (B) interaction between multivalent ligands and receptor through statistical effects; (C) interaction between multivalent ligands and receptor mainly through multivalent effects.

Figure 6

Figure 6

Schematics of polymer therapeutics: (A) multivalent binding between multivalent ligands and protein receptors; (B) multivalent binding between multivalent ligands and cell surface receptors.

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