Graft-and-block copolymers are comprised of two different polymers grafted together. A number of patents already exist for different combinations of polymers with different reactive groups. The product exhibits properties of both individual components which adds a new dimension to a smart polymer structure, and may be useful for certain applications. Cross-linking hydrophobic and hydrophilic polymers results in formation of micelle-like structures that can protectively assist drug delivery through aqueous medium until conditions at the target location cause simultaneous breakdown of both polymers.
A graft-and-block approach might be useful for solving problems encountered by the use of a common bioadhesive polymer, polyacrylic acid (PAAc). PAAc adheres to mucosal surfaces but will swell and degrade rapidly at pH 7.4, resulting in rapid release of drugs entrapped in its matrix. A combination of PAAc with another polymer that is less sensitive to changes at neutral pH might increase the residence time and slow the release of the drug, thus improving bioavailability and effectiveness.
Hydrogels are polymer networks that do not dissolve in water but swell or collapse in changing aqueous environments. They are useful in biotechnology for phase separation because they are reusable or recyclable. New ways to control the flow, or catch and release of target compounds, in hydrogels, are being investigated. Highly specialized hydrogels have been developed for the delivery and release of drugs into specific tissues. Hydrogels made from PAAc are especially common because of their bioadhesive properties and tremendous absorbency.
Enzyme immobilization in hydrogels is a fairly well-established process. Reversibly cross-linked polymer networks and hydrogels can be similarly applied to a biological system where the response and release of a drug is triggered by the target molecule itself. Alternatively, the response might be turned on or off by the product of an enzyme reaction. This is often done by incorporating an enzyme, receptor or antibody, that binds to the molecule of interest, into the hydrogel. Once bound, a chemical reaction takes place that triggers a reaction from the hydrogel. The trigger can be oxygen, sensed using oxidoreductase enzymes, or a pH-sensing response. An example of the latter is combined entrapment of glucose oxidase and insulin in a pH-responsive hydrogel. In the presence of glucose, the formation of gluconic acid by the enzyme triggers release of insulin from the hydrogel.
Two criteria for this technology to work effectively are enzyme stability and rapid kinetics (quick response to the trigger and recovery after removal of the trigger). Several strategies have been tested in type 1 diabetes research, involving the use of similar types of smart polymers that can detect changes in blood glucose levels and trigger production or release of insulin. Likewise, there are many possible applications of similar hydrogels as drug delivery agents for other conditions and diseases.
Smart polymers are not just for drug delivery. Their properties make them especially suited for bioseparations. The time and costs involved in purifying proteins might be reduced significantly by using smart polymers that undergo rapid reversible changes in response to a change in medium properties. Conjugated systems have been used for many years in physical and affinity separations and immunoassays. Microscopic changes in the polymer structure are manifested as precipitate formation, which may be used to aid separation of trapped proteins from solution.
These systems work when a protein or other molecule that is to be separated from a mix, forms a bioconjugate with the polymer, and precipitates with the polymer when its environment undergoes a change. The precipitate is removed from the media, thus separating the desired component of the conjugate from the rest of the mixture. Removal of this component from the conjugate depends on recovery of the polymer and a return to its original state, thus hydrogels are very useful for such processes.
Another approach to controlling biological reactions using smart polymers is to prepare recombinant proteins with built-in polymer binding sites close to ligand or cell binding sites. This technique has been used to control ligand and cell binding activity, based on a variety of triggers including temperature and light.
Future Applications
It has been suggested that polymers might be developed that can learn and self-correct behavior over time. Although this might be a far distant possibility, there are other more feasible applications that appear to be coming in the near future. One of these is the idea of smart toilettes that analyze urine and help identify health problems. In environmental biotechnology, smart irrigation systems have been also been proposed. It would be incredibly useful to have a system that turns on and off, and controls fertilizer concentrations, based on soil moisture, pH and nutrient levels. Many creative approaches to targeted drug delivery systems that self-regulate based on their unique cellular surroundings, are also under investigation.
There are obvious possible problems associated with the use of smart polymers in biomedicine. The most worrisome is the possibility of toxicity or incompatibility of artificial substances in the body, including degradation products and byproducts. However, smart polymers have enormous potential in biotechnology and biomedical applications if these obstacles can be overcome.
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