Enzyme responsive polymers polymer particles

Thronton, P.D. Mart, R.J. Ulijn, R.V. Enzyme-responsive polymer hydrogel particles for controlled release. Adv. Mater. 2007,19 (9), 1252-1256. 

Enzyme-responsive polymers can be classified in various ways, for example according to their structure, function or response type or mechanism. Here, we classify enzyme-responsive polymers, according to their structural elements, into polymer hydrogels, supramolecular polymers, polymer particles and self-immolative polymers. The general properties of these classes and their importance in biomaterial apphcations will be introduced. Using examples from the recent literature, we will demonstrate how enzyme responsiveness can be incorporated into these materials. 

Enzyme-triggered release of bioactive molecules from a polymer based material is possibly the most intensely researched application for enzyme-responsive polymers. Such delivery systems typically employ vehicles such as micelles, solid particles and capsules to contain and protect a drug and deliver it to the site of action either by injection directly into the diseased tissue or by circulation through the blood stream. At the site of action, the enzyme will degrade the polymer, cause disassembly of the micelle or swell the particle and thus cause release of the drug into the environment. 

Responsive polymer bmshes are not only investigated on planar substrates, but can also be used to decorate nanoparticles (Figure 5.13). Here, the key biomedical application is the accommodation (immobilize) of biofunctional moieties such as proteins or enzymes (Wittemann Ballauff, 2006 Wittemann, Haupt, BaUauff, 2003). If there is sufficient attraction between a protein and a polymer brush to overcome excluded volume effects (the antifouling properties of the brush), much larger amounts of protein can accumulate inside a brnsh layer than can be adsorbed onto just the particles surface. The role of the attached polymer chains is thus to strongly increase the available surface area. In Fignre 5.13, we schematically show a spherical polymer brush filled with adsorbed nanoparticles. Because, protein molecules inunobilized by polymers are found to be relatively weakly bound, they keep their conformation and (enzymatic)... 

Key words enzyme-responsive materials (ERMs), regenerative medicine and drug delivery applications, polymer hydrogels and scaffolds, supramolecular particles and self-assembly polymer particles. 

The introduction of enzyme-sensitive cross-links in an otherwise nonenzyme-responsive polymer such as PEG is frequently used to prepare enzyme-responsive polymer hydrogels and polymer particles. Because of their versatility and natural predisposition as enzyme substrates, short peptide sequences are almost exclusively used as cross-linkers, although dex-tran has also been used (Klinger et al., 2012). They can be readily changed to respond to a variety of proteases such as matrix metalloproteinases,plasmin or trypsin (Lutolf et al., 2003a Yang et al, 2010). In most cases, the peptides have to be modified at the termini to introduce reactive groups that are able to react with the polymer. 

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