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International Journal of Engineering Technology, Management and Applied Sciences
www.ijetmas.com September 2014, Volume 2 Issue 4, ISSN 2349-4476
104 Rushi Ghizal, Gazala Roohi
Smart Polymers and Their Applications
Rushi Ghizal Gazala Roohi Fatima Seema Srivastava
Physics Department. Physics Department. Physics Department. Integral University, Kursi Road. Integral University, Kursi Road, Integral University, Kursi Road
Lucknow-226066, U.P, India. Lucknow-226066, U.P, India. Lucknow-226066, U.P, India.
ABSTRACT
Smart polymers are materials that respond to small external stimuli. These are also referred as “stimuli responsive”
materials or “intelligent” materials. The stimuli include salt, UV irradiation, temperature, pH, magnetic or electric field,
ionic factors etc. Smart polymers are very promising applicants in drug delivery, tissue engineering, cell culture, gene
carriers, textile engineering, oil recovery, radioactive wastage and protein purification. The study is focused on the entire
features of smart polymers and their most recent and relevant applications.
Keywords: Smart polymers, Stimuli responsive materials, drug delivery, tissue engineering.
INTRODUCTION
The term “smart polymers” encompasses a wide spectrum of different compounds with unique potential for various
applications. The characteristic features that actually make these polymers “smart”, is their ability to respond to very slight
changes in the surrounding environment. The uniqueness of these materials lies not only in the fast microscopic changes
occurring in their structure but also these transitions being reversible, i.e, these systems are able to recover their initial state
when the sign or stimuli ends [1]. Smart polymers are biocompatible, strong, resilient, flexible, easy to sharpen and color.
They keep the drug’s stability and are easy to manufacture, good nutrient carriers to the cells, easily charged using adhesion
ligands and is possible to inject them in vitro as liquid to create a gel with the body temperature [2].
The responses are manifested as changes in one or more of the following- shape, surface characteristic, solubility,
formation of an intricate molecular assembly, a sol-gel transition and others. The environmental trigger behind these
transitions can be either change in temperature [3-8], pH shift [3,9,10], increase in ionic strength, presence of certain
metabolic chemicals, addition of an oppositely charged polymer and polycation-polyanion complex formation, changes in
electric [11] and magnetic field [12], light [13-14] or radiation forces. Smart polymers are becoming increasingly more
prevalent as scientist learn about the chemistry and triggers that induce conformational changes in polymer structures and
devise ways to take advantage of and control them. New polymeric materials are being chemically formulated that sense
specific environmental changes in biological systems.
1. CLASSIFICATION OF SMART POLYMERS
Smart polymers can be classified according to their physical features or to the stimuli they’re responding. Regarding
the physical shape, they can be classified as free linear chain solutions, reversible gels covalently cross linked and
polymer chain grafted on a surface [15].
The signs or stimuli that trigger the structural changes on smart polymers can be classified in three groups, 1.
Physical stimuli(temperature, ultrasounds, light, mechanical stress), 2. Chemical stimuli(pH and ionic strength) and, 3.
Biological stimuli(enzymes and biomolecules). Table1, presents Smart Polymers according to the stimuli they’re
responding.
International Journal of Engineering Technology, Management and Applied Sciences
www.ijetmas.com September 2014, Volume 2 Issue 4, ISSN 2349-4476
105 Rushi Ghizal, Gazala Roohi
Table1. Stimuli-Responsive Smart Polymeric Materials
Type of Stimulus
Responsive Polymer Material Reference(s)
pH *dendrimers
*poly(L-lysine)ester
*poly(hydroxyproline)
*Lactose-PEG grafted poly(L-lysine) nanoparticle
*poly(L-lysine)-g-poly(histidine)
*poly(propyl acrylic acid)
*poly(ethacrylic acid)
*polysilamine
*Eudragit S-100
*Eudragit L-100
*Chitosan
*PMAA-PEG copolymer
[16-19]
[20]
[21]
[22]
[22]
[23]
[23]
[24]
[25]
[26]
[27]
[28]
Ions *alginate (Ca2+
)
*chitosan (Mg2+
)
[29]
[30]
Organic solvent Eudragit S-100 [31]
Temperature PNIPAAm [32]
Magnetic field PNIPAAm hydrogels containing ferromagnetic
material PNIPAAm-co-acrylamide.
[33-34]
Ru2+
→Ru3+
(redox reaction) PNIPAAm hydrogels containing Tris (2,2-bipyridyl)
ruthenium (II).
[35]
Temperature (sol-gel transition) *poloxamers
* chitosan-glycerol phosphate-water
* prolastin
* hybrid hydrogels of polymer and protein domains
[36-38]
[39]
[40]
[41-42]
Electric potential polythiophen gel [43]
IR radiation poly(N-vinyl carbazole) composite [44]
UV radiation Polyacrylamide crosslinked with 4-(methacryloylamino)
azobenzene Polyacrylamide-triphenylmethane leuco
derivatives.
[45-46]
Ultrasound dodecyl isocyanate-modified PEG-grafted poly(HEMA). [47]
2. DISCUSSION ON SOME TYPES OF SMART POLYMERS
2.1. pH sensitive smart polymers
The pH sensitive polymers are able to accept or release protons in response to pH changes. These polymers contain in
their structure acidic groups (carboxylic or sulphonic) or basic groups (amino salts) [48]. In other words pH sensitive
polymers are polyelectrolytes that have in their structure acid or basic groups that can accept or release protons in
response to pH changes in the surrounding environment.
In the human body we can see remarkable changes of pH that can be used to direct therapeutic agents to a specific
body area, tissue or cell compartment (Table 2). These conditions make the pH sensitive polymers the ideal
pharmaceutical systems to the specific delivery of therapeutic agents.
2.1.1. Polymers with functional acid groups
Polyacids or polyanions are pH sensitive polymers that have great number of ionizable acid groups in their structure
(like carboxylic acid or sulphonic acid). The carboxylic groups accept protons at low pH values and release protons at
high pH values [50]. Thus when the pH increases the polymer swells due to the electrostatic repulsion of the negatively
charged groups. The pH in which acids become ionized depends on the polymer’s pKa (depends on polymers
composition and molecular weight).
International Journal of Engineering Technology, Management and Applied Sciences
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106 Rushi Ghizal, Gazala Roohi
Table2. pH values from several tissues and cells compartments [49].
Tissue/Cell compartment
pH
Blood 7.4-7.5
Stomach 1.0-3.0
Duodenum 4.8-8.2
Colon 7.0-7.5
Lysosome 4.5-5.0
Golgi complex 6.4
Tumor-Extracellulare medium 6.2-7.2
Examples of polyanions are poly(acrylic acid)(PAA) or poly(methacrycic acid) (PMAA). Thus in oral drug delivery
system, the poly(acrylic acid) polymer retains the drug on the presence of acid pH (stomach), delivering it in alkaline pH
(small intestine). The drug delivery occurs due to the ionization of pendant groups of carbolic acid, forcing the polymer
to swell.
2.1.2. Polymers with functional basic groups
Polybases or polycations are protonated at high pH values and positively ionized at neutral or low pH values, i.e they
go through a phase transition at pH 5 due to deprotonation of the pyridine groups.
Example are poly(4-vinylpyridine)(PVP), poly(2-vinylpyridine) (PVAm), poly(2-diethylaminoethyl methacrlate)
(PDEAEMA), with amino groups in their structure which in acid environments gain proton and in basic environment
releases the protons.
2.2. Thermo-responsive polymers
These smart polymers are sensitive to temperature and change their microstructural features in response to change in
temperature. These are the most studied, most used and most safe polymers in drug administration systems and
biomaterials. Thermo-responsive polymers present in their structure a very sensitive balance between the hydrophobic
and the hydrophilic groups and a small change in the temperature can create new adjustments [51]. This type of system
exhibit a critical solution temperature at which the phase of polymer and solution is changed in accordance with their
composition. Those systems exhibiting one phase above certain temperature and phase separation below it possess an
upper critical solution temperature (USTC). On the other hand, polymer solutions that appear as monophasic below a
specific temperature and biphasic above it, generally exhibit the so called lower critical solution temperature (LCST).
These represent the type of polymers with most number of applications. If the polymeric solution has a phase below the
critical temperature, it will become insoluble after heating, i.e, it has one lower critical solution temperature (LCST).
Above the critical solution temperature (LCST), the interaction strengths (hydrogen linkages) between the water
molecules and the polymer become unfavorable, it dehydrates and a predominance of the hydrophobic interaction occurs
causing the polymer swelling [52]. The LCST can be defined as the critical temperature in which the polymeric solution
shows a phase separation, going from one phase (isotropic state) to two phases (anisotropic phases).
The polymers with a lower critical solution temperature (LCST) are mostly used in drug delivery systems. The
therapeutic agents as drugs, cells or proteins can be mixed with the polymer when this is on its ligand state (temperature
below the transition temperature) being able to be injected in the human body on the subcutaneous layer or in the
damaged area and forming a gel deposit on the area where it was injected after increasing the temperature [15]. This kind
of pharmaceutical system delivers the drug on a controlled way without being too invasive.
2.3. Polymers with Dual Stimuli-Responsiveness
These are the polymeric structures sensitive to both temperature and pH, they are obtained by the simple combination
of ionization and hydrophobic (inverse thermosensitive) functional groups [50]. This approach is mainly achieved by the
copolymerization of monomers bearing these functional groups, combining temperature sensitive polymers with
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107 Rushi Ghizal, Gazala Roohi
polyelectrolytes (SIPN IPN) [53] or by the development of new monomers that respond simultaneously to both stimuli
[54].
2.4. Light Sensitive Smart Polymers
Light can be considered as a clean stimulus that allows remote control without physical contact or a mechanical
apparatus. It is attractive because it enables one to change the geometry and dipole moment of photo-switching molecules
causing macroscopic variations of molecularly organized structures by small perturbations. These changes can effect
final properties such as wettability, permeability, charge, color, binding and alignment. A fine-tuning of these can be
done through a series of sophisticated techniques listed in Table 3.
Table3. A list of some techniques used to monitor morphology and property changes due to photo-irradiation.
Technique Property References
UV spectroscopy Isomerization [55]
Ellipsometry Variation of average thickness of sample in fair agreement
with the calculated geometries of the molecules
[56]
Surface Plasmon
Resonance Spectroscopy
Switching in real time under ambient conditions [57]
Contact angle
Measurement
Switching wetting of surfaces. [58]
Adsorption of
molecules/Particles from
solution.
Control of adsorption on surfaces. [58]
Atomic force microscopy Switching in individual molecule [56]
Kelvin probe
measurement
Changes in work function of Functionalized surfaces [59]
Measurement of electrical
properties
Azobenzene switching controls electrical properties of
Sams
[58]
Electrochemical methods Quantitative isomerization by cyclic Voltammetry [60]
Surface-enhanced Raman
spectroscopy
Isomerization on the surface [61]
Polymers which are sensitive to visible light are called as light sensitive polymers. Light is a desirable external
stimulus for drug delivery systems because it is inexpensive and easily controlled. Light-sensitive drug carriers are
fabricated from polymers that contain different photo-sensitizers such as azobenzene, stilbene and triphenylmethane.
Polymers that form two phase systems are potentially used in industrial bioseparation techniques. So many problems of
two phase system (like they cannot be recycled, require purification processes etc) have been overcome by using light
sensitive smart polymers. These systems are biocompatible, biodegradable, polymerizable and at least partially water
soluble macromers. The macromers include at least one water soluble region, at least a region which is biodegradable and
at least two free radical-polymerizable regions.
2.5. Phase sensitive smart polymers
Phase sensitive smart polymers are mainly used to prepare biocompatible formulations of proteins for controlled
delivery in biologically active and confarmationally stable form. The phase sensitive injectable polymeric systems have
many advantages over the conventional system such as ease of manufacturing conditions for sensitive drug molecules
and high drug loading capacity. In this approach a water insoluble biodegradable polymer such as poly(D,L-lactide) and
poly(D,L-lactide-co-glycoide) dissolve in pharmaceutically accepted solvent to which a drug is added forming a solution
or suspension. After injecting the formulation into the body the water miscible organic solvent dissipates and water
penetrates into the organic phase. This causes the phase separation and precipitation of the polymer forming a depot at
the site of injection [62-63]. Organic solvents used include hydrophobic solvents (such as triacetin, ethyl acetate and
benzylbenzoate) and hydrophobic solvents (such as N-methyl -2-pyrrolidone, tetraglycol). Major application of phase
International Journal of Engineering Technology, Management and Applied Sciences
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108 Rushi Ghizal, Gazala Roohi
sensitive smart polymer lies in lysozyme release, controlled release of several proteins and using of emulsifying agents in
phase sensitive formulations to increase the stability of drug [64].
2.6. Magnetic sensitive smart polymers
Magnetic drug delivery systems possess three main advantages: a) visualization of drug delivery vehicles, b) ability
to control and guide the movement of drug carriers through magnetic fields and c) thermal heating which has been used
to control drug release or produce tissue ablation. Magnetic drug carriers like magnetite, cobalt, ferrite and carbonyl iron
are mainly used and they are biocompatible, non-toxic and non-immunogenic [65]. Magnetic nanoparticles have also
been encapsulated within liposomes. Polyelectrolyte coated- liposomes were highly stable as they showed no significant
membrane disruption or leakage of encapsulated contents in the presence of detergent Triton TX-100 [66].
2.7. Multi stimuli responsive polymers
Polymers can also exhibit responsive behavior to multiple stimuli and numerous dual stimuli responsive systems have
been studied. Combinations of light and temperature, temperature and pH, light and electric field have been reported.
There are reports on triple stimuli responsive polymers that respond to light, heat and pH. Multistimuli responsive
polymeric materials can be obtained by the incorporation of different functional groups which are responding to different
stimuli.
3. POTENTIAL APPLICATION OF SMART POLYMERS
3.1. Smart drug delivery systems
The application of smart polymers for drug delivery shows great promise due to modulated or pulsating drug release
pattern to mimic the biological demand. Another important thing is that these operate fully automatically, without the
need of additional sensors, transducers, switches or pumps. Stimuli occurring externally of internally include
temperature, electric current, pH etc. When an enzyme is immobilized in smart hydrogels the product 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 environment signal (e.g pH change) and then into the mechanical signal (shrinking or
swelling) of smart gel. This effect of swelling or shrinking of smart polymer 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 beads depends upon the
gel state. These smart polymers become viscous and cling to the surface in a bioadhesive form therefore providing an
effective way to administer drugs, either topically or mucosae, over long timescales by dissolving them in solution,
which contains hydrophobic regions. Through this technique, efficiency and cost effectiveness is increased.
Most extensive efforts in this area have been made for developing insulin release system in response to high glucose
levels [67]. In an early approach, entrapped insulin was released from copolymers of allylglucose crosslinked with
Concanavalin A. In later designs, glucose oxidase has been used to generate H+
(in response to the presence of glucose)
and hence exploit pH –sensitive hydrogels. One common worry in all such cases is the slow response time. Thus, use of
superporous hydrogels with fast swelling-deswelling kinetics is a step in the right direction [68].
A pH responsive hydrogel composed of polymethacrylic acid grafted with polyethylene glycol has been evaluated in
vitro for calcitonin delivery [69]. This poly- peptide is a therapeutic agent for bone diseases like Paget’s disease,
hypercalcemia and osteoporosis. As the pH increased during the passage from stomach to upper small intestine, the
ionized pendant carboxyl groups caused electrostatic repulsion, the network swelled and the hormone was released.. The
release behavior showed that movement of polymer chains was a key factor that controlled the solute transport.
Qiu and Park [70] have also reviewed various hydrogels responsive to various stimuli. An example worth quoting
from their review uses the concept of release of antibiotics at the site and time of infection. The antibiotic, Gentamycin,
was attached to the polyvinyl alcohol backbone through peptide linkers. Infected wounds produced a higher
concentration of thrombin which snapped the peptide linkers and accelerated the release of the antibiotic.
3.2. Stimuli-responsive surfaces
The change in the 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
International Journal of Engineering Technology, Management and Applied Sciences
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109 Rushi Ghizal, Gazala Roohi
hydrophobic solid culture dishes and are usually detached from it by protease treatment, which also causes damage to
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 370
C, a substrate surface coated with grafted poly (N- Isopropylacrylamide) is
hydrophobic because this temperature is above the critical temperature of the polymer and cells grow well. However
when the temperature is decreased by 200
C, 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 the cultured cells as a single sheet. Cell–sheet is highly effective when transplant to
patients due to tight communication between cells and cells. This technology has recently been commercialized.
3.3. Tissue engineering
Tissue engineering is about delivering of appropriate cells for repair/or development of new tissues by use of scaffolds
[71-72]. Smart hydrogels constitute promising materials for such scaffolds for two reasons. Firstly, their interior
environment is aqueous. Secondly, they can release the cells at the appropriate place in response to a suitable stimulus.
Soluble pH and temperature-responsive polymers that overcome transition at physiological condition (370
C and/or
physiological pH) have been proposed as minimally invasive injectable systems. The soluble systems may be easily
injected, however they precipitate or gel in situ forming an implant of scaffold useful for tissue engineering [73-74, 15].
The ability of Poly-N-Isopropylacrylamide and it’s copolymers to exhibit hydrophilic /hydrophobic nature has
attracted many researchers to create surfaces for cell culture systems [75-76]. Various groups work on cell culture carrier
with or without the option of immobilizing bioactive molecules and subsequently releasing them. This technique may be
applied e.g in the transplantation of retinal pigment epithelial cell sheets, which can be recovered without any defects
[77].
Poly-N-Isopropylacrylamide based hydrogels are non-adherent below the LCST and adhere above the LCST; at high
temperature bioactive molecule can be entrapped and subsequently released upon lowering the temperature.
Temperature-sensitive hydrogels have gained considerable attention in the pharmaceutical field due to ability of the
hydrogels to swell or deswell as a result of changing the temperature of the surrounding fluid. Numerous researchers
studied various applications of these hydrogels such as on-off drug release regulations, biosensors and intelligent cell
culture dishes [78].
3.4. Reversible bio-catalyst
Smart polymers can be used to design reversible soluble/insoluble biocatalyst. Reversible biocatalyst catalyze on
enzyme reaction in their soluble state and thus can be used in reactions with insoluble/poorly soluble substrates.
Reversible soluble biocatalyst are formed by the phase separation of smart polymers in aqueous solutions following a
small chance in the external conditions, when the enzyme molecule is bound covalently to polymer. As the reaction is
complete, the conditions are changed to cause the catalyst to precipitate so that it can be separated from the product and
be reused. Stimuli that are used to reuse include pH, temperature, ionic strength and addition of chemical species like
calcium.
For example, trypsin immobilized on a pH –responsive copolymer of methylmethacrylate and methacrylic acid is used
for repeated hydrolysis of casein. Similarly simplex cells are immobilized inside beads of the thermoresponsive polymer
gel as a biocatalyst. A biocatalyst sensitive to magnetic field is produced by immobilizing invertase and γ-Fe2O3 in
Poly(N-Isopropylacrylamide-co-acrylamide) gel. The heat generated by exposure of γ-Fe2O3 to a magnetic field causes
the gel to collapse, which is followed by a sharp decrease in the rate of sucrose hydrolysis.
Polymer bound smart catalyst are useful in waste minimization, catalyst recovery and catalyst reuse. Polymeric smart
coatings have been developed that are capable of both detecting and removing hazardous nuclear contamination. Such
applications of smart materials involve catalyst chemistry, sensor chemistry and chemistry relevant to decontamination
methodology are applicable to environmental problems.
3.5. Smart polymers in textile engineering
A series of polymer fibers with a shape memory effect were developed. Firstly, a set of shape memory polyurethanes
with very hard segment content were synthesized. Then the solutions of the shape memory polyurethanes were spun into
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110 Rushi Ghizal, Gazala Roohi
fibers through wet spinning. It was found that the fibers showed less shape fixity but more shape recovery compared with
thin films. Further investigations revealed that the recovery stress of fibers was higher than that of thin films. The smart
fibers may exert the recovery forces of the shape memory polymers to an extreme extent in the direction of the fiber axis
and therefore provide a possibility for producing high-performance acutators [79].
3.6. Glucose sensors
The major application of smart polymers is in the fabrication of insulin delivery system for the treatment of diabetic
patients. Many devices have been employed for the purpose of delivering exact amount of insulin at the exact time of
need and all of them have glucose sensors usually built into the system. Glucose oxidase is mostly used in glucose
sensing.
3.7. Smart polymers in oil recovery
Water in a well can be blocked by the use of smart polymeric materials that inhibit the water influxes. Fracturing
fluids are used to fill the artificial fractures of oil layers. This artificial system has a high permeability with respect to the
oil comparison with the rocks [80].
3.8. Bio-separations
Conjugate systems have been used in physical affinity separation and immunoassays. In affinity precipitation of
biomolecule, the bioconjugate is synthesized by coupling a ligand to a water soluble smart polymer. The ligand polymer
conjugate selectively binds the target protein from the crude extract and the protein-polymer complex is precipitated from
the solution by the changes in the environment like pH, temperature, ionic strength or addition of some reagents. Finally
the desired protein is dissociated from the polymer and the later can be recovered from the reuse for another cycle.
Various ligands like protease inhibitors, antibiotics, nucleotides, metal chelates, carbohydrates have been used in affinity
precipitation.
3.9. Biomimetic actuators
There have been attempt to mimic the efficient conversion of chemical energy into mechanical energy in living
organisms. A cross linked gel of Poly(vinyl alcohol) chains entangled with the polyacrylic acid chains has good
mechanical properties and shows rapid electric field association bending deformations: a gel rod of 1mm diameter bends
semi circularly within 1 sec on the application of electric field. Polymer gels capable of mechanical response to electric
field have also been developed using the cooperative binding of the positively charged surfactant molecule to the
polyanionic polymer poly(2 acrylamido- 2 methyl-1-propane sulfonic acid). Copolymer gels consist of N-
Isopropylacrylamide and acrylic acid would be useful for constructing biochemomechanical systems. A pH induced
change in the –COOH ionization of acrylic acid alters the repulsive forces, the attractive force is produced by
hydrophobic interactions arising from the dehydration of N-Isopropylacrylamide moieties. The biomimetic actuators
could be used in future soft machines that are designed using more biological than mechanical principles.
3.10. Molecular gates and switches
The Hoffman group has developed the concept of conjugating a stimulus-responsive polymer/hydrogel to a protein at
a site near it’s ligand recognition site [81]. The carefully controlled placement of the polymer ensures that when a
stimulus is applied, the collapsing/swelling of a gel causes the active site of the protein to be blocked /unblocked. In one
of the early examples Poly N-Isopropylacrylamide was linked to streptavidin at a site located just above its biotin binding
site [81]. When the temperature is raised above the LCST of the hydrogel, it collapses covering the active site. Biotin can
no longer bind to streptavidin, thus the polymer effectively acts as “molecular gate”. The concept of physical blocking of
recognition sites by a collapsed form has also been utilized in design of photoswitches for ligand association which might
be useful in bioprocessing, biosensors.
3.11. Protein folding
In order to attain the native structure and function of proteins, the refolding process is a major challenge in currently
ongoing biochemical research. Using smart polymer reduces the hydrophobicity of surfactant which facilitates or hinders
the conformational transition of unfolded protein, depending upon the magnitude of unfolded protein. Refolding of
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bovine carbonic anhydrase was examined in presence of PPO-Ph-PEG at various temperatures. The refolding yield of
carbonic anhydrase was strongly enhanced and aggregate formation of PPO-Ph-PEG at specific temperature of 50-550
C.
Eudragit S-100, a pH sensitive smart polymer is supposed to increase the rate of refolding and refolding percentage of
denatured protein. This was found to assist refolding of α-chymotrypsin, which is known to bind to the polymer rather
than non-specifically [82-83].
3.12. Smart polymer in protein purification
The use of smart polymers for the concentration of protein solutions and for the isolation as well as purification of
biomolecules. Recombinant thermostable lactate dehydrogenase from the thermophile Bacillus stearother mophilus was
purified by affinity partitioning in an aqueous two phase polymer system formed from by dextran and a copolymer of N-
vinyl caprolactam and 1-vinyl imidazole. The enzyme partitioned preferentially into the copolymer phase in presence of
Cu ions. The enzyme lactate dehydrogenase from porcine muscle has better access to the ligands and binds to the
column. With the decrease in temperature the polymer molecules undergo transition to a more expanded coil
conformation. Finally, the bound enzyme is replaced by the expanded polymer chains. This system was used for lactate
dehydrogenase purification [84].
3.13. Smart polymer in gene therapy
The aim of gene therapy includes curing genetic diseases and viral infections, slowing down tumor growth and
stopping neurodegenerative diseases [85]. The basic principal is inserting the desired genetic material into the cell and
finding an efficient method for the delivery of the gene. Two types of nonviral (synthetic) gene carrier, lipids and
polymers have been used. Both have to be cationic in nature in order to form complexes with anionic DNA and the
complex has to have net positive charge to interact with the anionic cell membrane and undergo endocytosis. The design
has to conform two contradictory requirements during endocytosis. While attaching to the coil and forming endosome,
the binding between the carrier and the DNA has to be quite high. On the other hand, for DNA to move into nucleus to
initiate transcription the complex should be easy to dissociate. It is here that the stimuli sensitive polymers are uniquely
suited to fulfill the dual requirement, as the stimulus can control the binding to DNA. Further more selective gene
expression is possible in terms of site, timings and duration by using light- or temperature- sensitive polymer.
Godbey and Mikos reviewed some of the advances in nonviral gene delivery research [86], describing the use of
poly(ethylenimine)(PEI) and poly(L-lysine)(PLL) as two of the most successful candidates for this application. PEI is
highly cationic synthetic polymer that condenses DNA in solution, forming complexes that are readily endocytosed by
many cell types. Chitosan, a biocompatible and reabsorbable cationic aminopolysaccharide has also extensively been
used as DNA carrier. Hoffman’s group has dedicated great efforts to obtain new delivery systems to introduce efficiently
biomolecules to intracellular targets [87-89]. They mimicked the molecular machinery of some viruses and pathogens
that are able to sense the lowered pH gradient of the endosomal compartment and become activated to destabilize the
endosomal membrane. This mechanism enhances protein or DNA transport to the cytoplasm from intracellular
compartments such as endosome. They demonstrated the utility of Poly(2-propylacrylic acid)(PPAA) to enhance protein
and DNA intracellular delivery.
3.14. Smart polymer reduces radioactive waste
Scientist in Germany and India are reporting the development of a new polymer that reduces the amount of
radioactive waste produced during routine operation of nuclear reactor. In the study the researchers created an absorbent
material that unlike unconventional ion exchange resins has the unique ability of disregarding iron bases ions. The
polymers high selectivity increases it’s appeal [90].
3.15. Stimuli-responsive surfaces
The change in surface properties of a thermo-responsive polymer 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 causes damage to the cells. This is rather
International Journal of Engineering Technology, Management and Applied Sciences
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112 Rushi Ghizal, Gazala Roohi
an inefficient way in which some detached cells are able to adhere onto new dishes because the rest are damaged. At
temperature of 370
C, a substrate surface coated with grafted poly N-Isopropylacrylamide is hydrophobic because this
temperature is above the critical temperature of the polymer and the cells grow well. However when the temperature is
decreased to 200
C, resulting the surface to become hydrophilic so that 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 technology has recently been commercialized.
3.16. In Biotechnology And Medicine
Smart polymers may physically mixed with or chemically conjugated to biomolecules to yield a large family of
polymer biomolecule to yield a large family of polymer-biomolecule system that can respond to biological as well as to
physical and chemical stimuli. Biomolecules that can be polymer conjugated include proteins and oligopeptides, sugars,
polysaccharides, single and double stranded oligonucleotides, DNA plasmids, simple lipids, phospholipids and synthetic
drug molecule. These polymer-biomolecule complexes are referred as affinity smart biomaterials or intelligent
bioconjugates. Also such polymer have been used in developing smart surfaces and smart hrdrogels that can respond to
external stimuli. Such polymeric biomaterials have shown a range of different applications in the field of biotechnology
and medicine. The researchers have used these polymers for biomedical applications to downstream processing and
biocatalyst.
The latest thrilling breakthrough achieved by the group of Stayton and Hoffman, at the university of Washington,
USA. The researchers developed a clever way to use smart polymers that provide size selective switches to turn proteins
on and off.
3.17. Autonomous flow control in microfluidics
The concept of ‘lab in a chip’ has evolved out of efforts to miniaturize analytical instruments. By using
photolithography on a chip, one can create microchannels and work with very small volumes. Smart materials show
considerable promise in designing microactuators for autonomous flow control inside these microfluidic channels. Saitoh
et al [91] have explored the use of glass capillaries coated with Poly N Isopropylacrylamide for creating an on/off valve
for the liquid flow. Below LCST the PNIPAm coated capillary allowed the flow of water, above LCST the flow was
blocked as the coating was now hydrophobic. Beebe et al [92], on the other hand used a pH sensitive methacrylate to
control the flow inside the microchannels. The hydrogel based microfluid valve opened or closed depending upon the pH
of the solution. The design has the potential of being self regulating/antonomous since the valve can be controlled by
feedback of H+
produced or consumed in the reaction. Undoubtedly we will see many other innovative designs foe such
applications in coming years.
4. CONCLUSION
In this article we have provided only a glimpse into the complexities and utility of smart polymeric materials. We
have strived to illustrate the versatility and potential of these materials. Drug design and medicine will profit both
financially and in terms of providing high quality health care, with the ability to precisely craft artificial organs and drug
delivery vehicles that “intelligently” interface with the cells and organs. An area of key interest to the smart polymeric
biomaterial field is the immune system. For example, using smart materials one could imagine ways to regulate the
immune responses to control hypersensitivity without impairing the overall immune system. Smart materials are poised
for takeoff and will certainly promise an exciting future.
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