Enzyme-sensitive polymers

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. 

Methods for the preparation of enzyme-sensitive polymer conjugates. 

Enzyme-sensitive polymers have been exploited freqnently and they have become one of the most important branches of drug delivery systems. Zhang et al. 

FIGURE 1.5. Schematic drawing showing the use of a temperature sensitive polymer to control access to the active sites of an enzyme. Access is denied when the polymer (dotted line) is in the crystalhne state (left), and allowed when the polymer is in the flexible state (right). 

Irradiation at >320 nm releases from the polymer, whether insoluble or water-soluble, free oligosaccharides in very high yields. A simple illustration of such a sequence carried out with either insoluble 2-aminoethyl-substituted poly(acrylamide) beads or with water-soluble, substituted poly(vinyl alcohol) is presented in Scheme 9 the isolated overall yield of lactose was 29.9% (soluble-polymer approach). The synthesis on light-sensitive polymers facilitates the isolation of products, which is important from the preparative point of view and as a tool for the study of enzymes, permitting efficient comparison of acceptor specificity and being capable of demonstrating de novo synthesis. 

Enzyme-sensitive supramolecular polymers also hold promise in analytical applications such as the screening of enzyme inhibitors. A simple visual assay based on the hydrogelation of small molecules has been developed for screening the activities of inhibitors of enzymes like acid phosphatase. A number of inhibitors for... 

The principle upon which this approach is based is an enzyme-substrate reaction that produces a change in pH and a hydrolytically labile, pH-sensitive polymer containing dispersed therapeutic agent that can vary the erosion rate and concomitant drug release in response to that pH change. Figure 1 shows two types of drug... 

The device shown in Figure 1(a) consists of a pH-sensitive polymer surrounded by a hydrogel containing immobilized enzyme. As the enzyme substrate diffuses from the external environment into the hydrogel and is converted to either an acidic or basic product, the pH within the hydrogel either increases or decreases and the polymer then responds to that pH change by altering its erosion rate. 

Wiemann T, Taubken N, Zehavi U, Thien J, Enzymic synthesis of N-acetyllactosamine on a soluble, light-sensitive polymer, Carbohydr. Res., 257 C1-C6, 1994. 

In spite of these formidable challenges, the attractiveness of oral route has fueled the exploration of an incredibly diverse set of strategies to deliver proteins and peptides and the subject has been exhaustively reviewed. The various approaches include permeation enhancers, enzyme inhibitors, mucoadhesives, multifunctional matrices that simultaneously incorporate the above strategies, enteric coatings that offer protection from the acidic environment of the stomach, encapsulation (liposomes, microspheres, and nanoparticles), pH-sensitive polymers, microemulsions, carriers (delivery agents), and protein modification either to simply enhance permeability or to exploit specific transporters. While proof-of-concept has been demonstrated with most of these delivery systems in animal... 

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