________________________________________
Life is polymeric- the most important components of living cell; proteins, carbohydrates, nucleic acids are polymers. The functions of living cells are regulated by these biopolymers that form the basis around which all major natural processes are controlled. Nature use polymers both as constructive elements and parts of complicated cell machinery. The salient feature of functional biopolymers is their all-or-none or at least highly nonlinear response to external stimuli. Small changes happens in response to varying parameter until the critical point is reached, then the transition occurs in the narrow range of the parameter varied and after the transition is completed, there is no significant further response of the system. Such nonlinear response of biopolymers is warranted by highly cooperative interactions. Despite the weakness of each particular interaction taking place in a separate monomer unit, these interactions when summed through hundreds and thousands of monomer units could provide significant driving forces for the processes occurring in such systems. Understanding of the mechanism of cooperative interactions in biopolymers has opened floodgates for attempts to mimic cooperative behavior of the biopolymers in synthetic systems. Last two decades witnessed the appearance of synthetic functional polymers, which respond in some desired way to a change in temperature, pH, electric or magnetic fields or some other parameters. These polymers were nicknamed stimuli-responsive. The name 'smart polymers' was coined due to the similarity of the stimuli-responsive polymers to the biopolymers. There is a strong belief that nature has always been striving for smart solutions in creating life. The goal for the scientists is not only to mimic biological processes, and therefore understand them better, but also to create novel species and invent new processes. Recent developments have shown an explosive growth in the subject where smart polymeric materials are being tailor made for application in biotechnology and medicine.
Of special interest are two most common smart polymer systems with sharp response to external stimuli and thus promising enormous potential in biotechnology, bioengineering and medicine. These systems are developed from pH- and temperature-sensitive smart polymers. For applications, these polymers are utilized in many forms, as can be dissolved in aqueous solution, adsorbed or grafted on aqueous-solid interfaces, or cross-linked in the form of hydrogels.
Smart drug delivery systems: The application of the smart polymers for drug delivery shows great promise due to modulated or pulsatile drug release pattern to mimic biological demand. Stimuli occurring externally or internally include temperature, photoirradiation, electric current, pH, and metabolic chemicals. When an enzyme is immobilized in smart hydrogels, the products of enzymatic reaction could themselves trigger the gel’s phase transition. It would then be possible to translate the chemical signal (e.g., presence of substrate) into the environmental signal (e.g. pH change) and then into the mechanical signal, namely shrinking or swelling of smart gel. The swelling or shrinking of smart hydrogel beads in response to small change in pH or temperature can be used successfully to control drug release, because diffusion of the drug out of the beads depends on the gel state. When a smart polymer integrated into microcapsule wall or a liposomal lipid bi-layer, the conformational transition of the polymer affects the integrity of the microcapsule or liposome and allows the regulated release of the drug loaded into the microcapsule or liposome. In a temperature sensitive polymer, a dilute solution (1-3%) of the polymer is watery liquid, while on warming to body temperature the solution gels, becoming viscous and clinging to surface in a ‘bioadhesive’ form.
The hydrogel therefore provides an effective way to administer drugs, either topically or mucosae, over longer timescales than otherwise possible, by dissolving them in a solution of the hydrogel, which also contains hydrophobic regions. By using such drug formulations incorporated into hydrogels pharmaceutical companies will be able to increase the efficiency, cost-effectiveness and range of applications for existing therapeutics.
As an intelligent drug delivery scheme, the development of glucose-sensitive insulin-releasing system for diabetes therapy has become a popular model for the systems using smart polymers. There have been several schemes which researchers developed over the years for the intelligent release of insulin. One latest model explains how specific release of insulin can be achieved in response to glucose in the form of ‘chemical valve’. Glucose oxidase can be immobilized on a pH responsive poly(acrylic acid) layer grafted onto a porous polycarbonate membrane. Under neutral conditions, polymer chains are densely charged and have an extended conformation, preventing insulin transport through the membrane by blocking the pores. Upon exposure to glucose the pH drops and the polymer chains become protonated and adopt a more compact conformation. The blocking of pores is reduced and insulin is transported through the membranes. Membrane permeability can be regulated via the conformational changes of the poly(methacrylic acid)poly(2-ethylacrylic acid) or poly(N-isopropylacrylamide) grafted inside the pores.
Smart surfaces: The change in surface properties of the thermoresponsive polymers from hydrophobic above the critical temperature to hydrophilic below it has been used in tissue culture applications. Mammalian cells are cultivated on a hydrophobic solid culture dishes and are usually detached from it by protease treatment, which also cause damage to the cells. This is rather an inefficient way in that only some detached cells are able to adhere onto new dishes because the rest are damaged. At temperature of 37 0C, a substrate surface coated with grafted poly(N-isopropylacryalmide) is hydrophobic because the temperature is above the critical temperature of the polymer and the cells grow well. However, when the temperature is decreased to 20 0C, resulting the surface to become hydrophilic, the cells can be easily detached without any damage. The cells can be used for further culturing. The cells are detached maintaining the cell-cell junction. This enables the collection of cultured cells as a single "sheet". Cell-sheet is highly effective when transplanted to patients due to tight communication between cells and cells. This can be used for cell sheet engineering applications like in skin grafting or cornea transplant. The polymer grafted dishes can be re-used many times. This technology has recently now been commercialized. |