Enzyme responsive polymers drug delivery

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. 

Within their designed areas of application, however, the versatility of enzyme-responsive polymers is unmatched by any other stimuli-responsive materials. Enzyme-responsive polymers have found applications as cell supports, injectable scaffolds and drug delivery systems and have been integrated with other stimuli-responsive polymers to obtain materials with closely tailored stimuli-responsive characteristics. While research in the development of enzyme-responsive materials (ERMs) is still in its early... 

By nature, ERMs are inherently suitable for applications in the healthcare section. Despite being a young class of materials, some exciting applications have begun to emerge. Here, three applications for enzyme-responsive polymers are highlighted cell supports, injectable scaffolds and drug delivery devices. 

Rabito, M. R, Reis, A V., Freitas, A. D. R, Tambourgi, E. B.,Cavalcanti. 0. A (2012). A pH/enzyme-responsive polymer film consisting of Eudragit FS 30 D and arabinoxylane as a potential material formulation for colon-specific drug delivery system, Pharm. Dev. TechnoL, 17,429-436. 

Over the past 5 years, a number of researchers have started to explore and mimic these approaches in the laboratory. Enzyme-assisted formation of supramolecular polymers has several unique features. These include selectivity, confinement and catalytic amplification, which allow for superior control as observed in biological systems. These systems are finding applications in areas where supramolecular function is directly dictated by molecular order, for example in designed biomaterials for 3D cell culture, templating, drug delivery, biosensing, and intracellular polymerisations to control cell fate. Overall, biocatalytic production of supramolecular polymers provides a powerful new paradigm in stimuli-responsive nanomaterials. 

Stimuli-responsive polymers have gained increasing interest and served in a vast number of medical and/or pharmaceutical applications such as implants, medical devices or controlled drug delivery systems, enzyme immobilization, immune-diagnosis, sensors, sutures, adhesives, adsorbents, coatings, contact lenses, renal dialyzers, concentration and extraction of metals, for enhanced oil recovery, and other specialized systems (Chen and Hsu 1997 Chen et al. 1997 Wu and Zhou 1997 Yuk et al. 1997 Bayhan and Tuncel 1998 Tuncel 1999 Tuncel and Ozdemir 2000 Hoffman 2002 en and Sari 2005 Fong et al. 2009). Some novel applications in the biomedical field using stimuli-responsive materials in bulk or just at the surface are shape-memory (i.e., devices that can adapt shape to facilitate the implantation and recover their conformation within the body to... 

Stimuli-responsive polymers and blends thereof for ophthalmic drug delivery systems are reviewed. These include polyaci ylic acid, temperature sensitive polymers, which are convertible into gels at body temperature, dual responsive polymers, ion-sensitive polymers, such as alginates, and enzyme-sensitive polymers, such as xanthan gum. 26 refs. 

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

Polymer hydrogels consist of a cross-finked network of hydrophilic polymers with a very large water content (up to 99%) (Wichterle and Lim, 1960).They are structurally similar to the ECM and have therefore frequently been used as ECM mimics (Fedorovich et al., 2007 Shoichet, 2010). Other biological applications include the use as injectable scaffolds, (temporary) cell culture supports and drug delivery matrices (Mano, 2008). For all these applications, the introduction of enzyme-responsive functionalities into the polymer hydrogel is attractive because it would either more closely mimic the ECM (which is itself enzyme responsive) or allow drug delivery in response to the presence of a specific enzyme. 

Dual-responsive polymer-based drug delivery vehicles offer even more versatility. Both temperature and enzyme-responsive micelles were formed from block polymers. While the thermoresponsive properties of the material allow it to be injected and subsequently form a reservoir in the body from where micelles enter the blood stream, the enzyme-responsive component allows triggered degradation of the micelles and release of the drug at the location of the diseased tissue (Garripelli et fl/.,2011). A doubly enzyme-responsive system can be obtained, for example, by designing polymer capsules with a shell that contains two layers. The two layers are degraded by different enzymes thus, proteins entrapped in the outer layer itself can be released upon exposure to the first enzyme, whereas the second enzyme destroys the capsule completely and liberates the proteins entrapped in the cavity of the vehicle (Itoh et al, 2008). 

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