smart polymers and their applications -...

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.




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).




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




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




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




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




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




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




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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