“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.” Smart polymeric Biomaterials: where Chemistry & Biology can merge By Ashok Kumar Smart polymeric materials respond by large constructive elements and parts of changes due to small changes in environment. complicated cell machinery. The salient The polymers that form these smart materials feature of functional biopolymers is their all- are referred as “smart” polymers or “stimuli- or-none or at least highly nonlinear response responsive” polymers or “environmentally” to external stimuli. Small changes happens in sensitive polymers. The smart polymers response to varying parameter until the undergo fast and reversible changes in the critical point is reached, then the transition microstructure from a hydrophilic to a occurs in the narrow range of the parameter hydrophobic state that are triggered by small varied and after the transition is completed, stimuli in the environment. The changes are there is no significant further response of the apparent at the macroscopic level as precipitate system. Such nonlinear response of formation from a solution accompanied by biopolymers is warranted by highly phase separation from aqueous solution or cooperative interactions. Despite the order of magnitude changes in the hydrogel weakness of each particular interaction size. This whole phenomenon is reversible, the taking place in a separate monomer unit, system returning to its initial state when the these interactions when summed through trigger is removed. The driving force behind hundreds and thousands of monomer units these transitions varies, with common stimuli could provide significant driving forces for including neutralization of charged groups by the processes occurring in such systems. either a pH shift or the addition of an Understanding of the mechanism of oppositely charged polymer, changes in the cooperative interactions in biopolymers has efficiency of the hydrogen bonding with an opened floodgates for attempts to mimic increase in temperature or ionic strength, and cooperative behavior of the biopolymers in collapse of hydrogels and interpenetrating synthetic systems. Last two decades polymer networks. Even the latest among these witnessed the appearance of synthetic have been the electric, magnetic, light or functional polymers, which respond in some radiation induced reversible phase transitions. desired way to a change in temperature, pH, Such property change of smart polymers has electric or magnetic fields or some other shown various applications in biological parameters. These polymers were nicknamed systems. stimuli-responsive. The name 'smart polymers' was coined due to the similarity of Life is polymeric the stimuli-responsive polymers to the biopolymers. There is a strong belief that The most important components of living nature has always been striving for smart cells; proteins, carbohydrates, nucleic acids are solutions in creating life. The goal for the polymers. The functions of living cells are scientists is not only to mimic biological regulated by these biopolymers that form the processes, and therefore understand them basis around which all major natural processes better, but also to create novel species and are controlled. Nature use polymers both as invent new processes. Recent developments 9 Fig. 1: pH-induced soluble-insoluble behaviour of synthetic (Eudragit S-100) and natural (chitosan) polymers have shown an explosive growth in the subject methacrylic acid (hydrophilic at high pH when where smart polymeric materials are being carboxy groups are deprotonated but more tailor made for application in biotechnology hydrophobic when carboxy groups are and medicine. Of special interest are two most protonated) precipitate from aqueous common smart polymer systems with sharp solutions on acidification to pH around 5 while response to external stimuli and thus promising copolymers of methyl methacrylate enormous potential in biotechnology, (hydrophobic part) with dimethylaminethyl bioengineering and medicine. These systems methacrylate (hydrophilic at low pH when are developed from pH- and temperature- amino groups are protonated but more sensitive smart polymers. For applications, hydrophobic when amino groups are these polymers are utilized in many forms, as deprotonated) are soluble at low pH but can be dissolved in aqueous solution, adsorbed precipitate at slightly alkaline conditions. or grafted on aqueous-solid interfaces, or Hydrophobically modified cellulose cross-linked in the form of hydrogels. deri vatives with pending carboxy groups, e.g. hydroxypropyl methyl cellulose acetate succinate are also soluble at basic conditions but precipitate in slightly acidic media. The pH- pH-sensitive smart polymers induced precipitation of smart polymers is very sharp and requires usually the change in pH not This group of smart polymers consists of the more than 0.5 units (Fig. 1). polymers for which transition between soluble The copolymerization of some specific and insoluble state is created by decreasing net monomers results in the synthesis of a pH- charge of the polymer molecule. The net sensitive polymer with reversible transition in charge can be decreased by changing pH to the physiological range of pH 7.0-7.5, thus neutralize the charges on the macromolecule making them more suitable for biological and hence to reduce the hydrophilicity systems. The charges on the macromolecule (increase the hydrophobicity) of the can also be neutralized by addition of an m a c r o m o l e c u l e . C o p o l y m e r s o f efficient counterion, e.g., low molecular weight methylmethacrylate (hydrophobic part) and counter ion or a polymer molecule with the 10 Fig. 2: Temperature response for thermo-sensitive polymers. (A) soluble phase(below LCST); (B) insoluble phase (above LCST) opposite charges. The latter systems are separation takes place. An aqueous phase combined under the name of polycomplexes. containing practically no polymer and a The cooperative nature of interaction between polymer enriched phase are formed. Both two polymers with the opposite charges makes phases can be easily separated by decanting, polycomplexes very sensitive to the changes in centrifugation or filtration. The temperature of pH or ionic strength. Many polymer systems phase transitions depends on polymer have thus been designed that can show the concentration and molecular weight (MW) reversible solubility property in any desired pH (Fig. 2). The phase separation is completely range where one needs to utilize them. reversible and the smart polymer dissolves in water when the temperature is reduced below the transition temperature. Thermo-sensitive smart polymers Two groups of thermo-sensitive smart polymers are most widely studied and used. The reversible solubility of thermosensitive · Poly(N-alkyl substituted acrylamides) and smart polymers is caused by changes in the most well-known of them, poly(N- hydrophobic-hydrophilic balance of isopropyl acrylamide) with transition uncharged polymer induced by increasing temperature of 32 °C. temperature or ionic strength. The uncharged polymers are soluble in water due to the · Poly(N-vinylalkylamides) like poly(N- hydrogen bonding with water molecules. The vinyliso-butyramide) with transition efficiency of hydrogen bonding reduces with temperature of 39°C or poly(N-vinyl increase in temperature. The phase separation caprolactam) with transition temperature 34- of polymer takes place when the efficiency of 36°C (depending on polymer molecular hydrogen bonding becomes insufficient for weight). solubility of macromolecule. On raising the Other polymers with different transition temperature of aqueous solutions of smart temperatures from 4-5°C for poly (N-vinyl polymers above a cer tain critical piperidine) to 100°C for poly(ethylene glycol) temperature(which is often referred as are available at present. Increase in the transition temperature, lower critical solution hydrophilicity of the polymer by incorporation temperature, LCST, or 'cloud point'), phase of hydrophilic co-monomers or coupling to 11 hydrophilic ligands, increases the transition Applications in Biotechnology and temperature while hydrophobic co-monomers Medicine and ligands have the opposite effect. Block copolymers with a thermosensitive Smart polymers may be physically mixed with “smart” part consisting of poly (NIPAAM) or chemically conjugated to biomolecules to form reversible gels on increase in temperature yield a large family of polymer-biomolecule while random copolymers separate from systems that can respond to biological as well as aqueous solutions by forming concentrated to physical and chemical stimuli. Biomolecules polymer phase. Thus, the properties of smart that can be polymer conjugated include polymers important for biotechnological and proteins and oligopeptides, sugars and medical applications could be controlled not polysaccharides, single and double-stranded only by the composition of co-monomers but oligonucleotides, DNA plasmids, simple lipids also by the polymer architecture. The phase and phospholipids and wide range of other transition at increased temperature of ligands and synthetic drug molecules. These thermosensitive