Soluble Smart Polymers

For the purposes of this section, smart polymers are defined as those which exhibit a nonlinear response such as a conformational change or a phase transition to an external stimulus. A very large number of responsive polymers have been reported in both open and patent literature, but the field continues to grow as new mechanisms of response and new types of polymer are emerging. 

The prototypical smart polymer is poly(N-isopropyl acrylamide) (P(NIPAM)), which exhibits an inverse temperature solubility profile in water, that is it is water-soluble below 32 °C but precipitates above 32 °C. The temperature at which this coil-to-globule phase transition occurs is known as the Lower Critical Solution Temperature (LCST), and conveniently this can be modified in P(NIPAM) by incorporation into the polymer chain of more hydrophobic or hydrophilic monomers. Owing to the fact that the LCST is close to body temperature and can readily be modified to just below or just above 37 °C through this co-monomer addition, P(NIPAM) polymers have been widely exploited in biomedical applications. The chemistries and applications of P(NIPAM) have been extensively reviewed elsewhere, [75-81] but even 15 years after one particularly well-cited review, many research groups are working with this remarkably versatile polymer [82-87]. 

Although P(NIPAM) materials have generated much interest in pre-clinical use, of particular note for the biomedical field are the recent reports from Lutz et al. on the synthesis and characterisation of a thermo responsive copolymer composed of oligo ethylene glycol units. 

In addition to temperature responses, polymer assembly and reorientation dependent on hydrophobic interactions and pH have been described. Block copolymer assembly into micellar structures is a potential means of eneapsulating a therapeutie, and if disassembly into unimers can be triggered at a biologieal site, a powerful means for selective drug delivery can be envisaged. 

Kataoka and co-workers and the Eisenberg group pioneered the use of polymeric micelles in drug delivery applications [93-96]. The Kataoka group prepared copolymer micelles with the concept that these should exhibit properties similar to those of natural drug delivery systems - that is viruses. However, unlike viruses, multi-component micelles coated with polyethylene glycol are fully biocompatible and cannot be identified inside the body as foreign substances. It was found that therapeutic molecules could be inserted, such 

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When soluble smart polymers are mixed with lysosome or cell suspensions, they may be phase-separated by a stimulus, and may interact with lysosomal or cell membranes by hydrophobic interactions [118]. After the conjugate interacts with the membranes and phase-separation take place, a gel may be formed and cells can be reversibly cultured on surfaces [119]. 

A variant on this theme is to attach a transition-metal complex of a smart polymer, the solubility of which can be dramatically influenced by a change in a physical parameter, e.g., temperature [23] (cf. Sections 4.6 and 4.7). Catalyst recovery can be achieved by simply lowering or raising the temperature. For example, block copolymers of ethylene oxide and propene oxide show an inverse dependence of solubility on temperature in water [24]. Karakhanov et al. [25] prepared water-soluble polymeric ligands comprising bipyridyl (bipy) or acetylacetonate (acac) moieties covalently attached to poly(ethylene glycol)s (PEGs) or ethylene oxide/propene oxide block copolymers 9 and 10. 

Another approach involves the covalent attachment of a metal complex to a (water-) soluble polymer [41]. By using thermoresponsive, smart , polymers the reaction can be performed in a homogeneous liquid phase and, after completion, the polymer-enlarged catalyst can be precipitated by adjusting the temperature [42]. 

Water-soluble polymer-bound catalysts represent an interesting alternative [86], in particular when they are attached to smart polymers, which can undergo a complete... 

A novel approach to immobilization of enzymes via covalent attachment is the use of stimulus-responsive smart polymers, which undergo dramatic conformational changes in response to small alterations in the environment, such as temperature, pH, and ionic strength [401 03], The most prominent example is a thermo-responsive and biocompatible polymer (poly-iV-isopropyl-acrylamide), which exhibits a critical solution temperature around 32°C, below which it readily dissolves in water, while it precipitates at elevated temperatures due to the expulsion of water molecules from its polymeric matrix. Hence, the biolransformation is performed under conditions, where the enzyme is soluble. Raising the temperature leads to precipitation of the immobilized protein, which allows its recovery and reuse. In addition, runaway reactions are avoided because in case the reaction temperature exceeds the critical solution temperature, the catalyst precipitates and the reaction shuts down. 

Boris, D., Z. Anatoliy, and Y. Elena. 2001. Application of water soluble polymers and their complexes for immunoanalytical purposes. Smart polymers. Boca Raton CRC Press. 

Two elements are required for successful affinity precipitation. The backbone of a smart polymer provides precipitation at the desired conditions (temperature, pH, ionic strength), and the biorecognition element is responsible for selective binding of the protein of interest. By proper choice of a smart polymer, precipitation could be achieved practically at any desired pH or temperature. For example, poly(A -acryloylpiperidine) terminally modified with maltose has an extremely low critical temperature (soluble below 4°C and completely insoluble above 8°C) and was used to purify thermolabile a-glucosidase (46). 

In order as the conformational changes induced by the external stimuli that occur at the molecular level to become macroscopic perceptible, the composition of the environmental medium is in such manner adjusted that the smart polymer to be in the proximity of phase transition. In this way small changes of stimuli will cause sharp phase transitions, which acts as an amplifier of the external signal [114]. Two typical examples of such phase transitions for soluble polymers and hydrogels are illustrated in Figure 4.24. The most frequent responses of to the stimuli action are listed in Table 4.6. 

Smart polymers Smart polymers include those polymers that act in response to very little change in the surrounding environment or to external stimulus, and thus they are also called environmentally sensitive or stimuli-responsive polymers or intelligent polymers. The unique character which makes these polymers intelligent and smart is their capability to respond even to minor changes in the nearby environment. These responses on one hand are fast and microscopic and on the other hand are reversible, which further enhance the imique character of these polymers. The response can be visualized or measured in terms of change in shape, solubility, sol-gel transition, surface characteristics and formation of complicated assembly of molecules, etc. [12,13]. This class of polymers will be discussed in detail later in the chapter. 

Due to difficulties in directly designing LCST polymers, water-soluble LCST type thermosensitive polymers have been used to create smart polymer systems controlled by guest molecules by incorporating molecular recognition sites. ... 

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