Smart polymer

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Smart polymers, stimuli-responsive polymers or functional polymers are high-performance polymers that change according to the environment they are in.

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Such materials can be sensitive to a number of factors, such as temperature, humidity, pH, chemical compounds, the wavelength or intensity of light or an electrical or magnetic field and can respond in various ways, such as altering color or transparency, becoming conductive or permeable to water or changing shape (shape memory polymers). Usually, slight changes in the environment are sufficient to induce large changes in the polymer's properties. [1] [2] [3]

Applications

Smart polymers appear in highly specialized applications and everyday products alike. They are used for sensors and actuators such as artificial muscles, the production of hydrogels, biodegradable packaging, and to a great extent in biomedical engineering . One example is a polymer that undergoes conformational change in response to pH change, which can be used in drug delivery. [4] Another is a humidity-sensitive polymer used in self-adaptive wound dressings that automatically regulate moisture balance in and around the wound. [5] [6]

The nonlinear response of smart polymers is what makes them so unique and effective. A significant change in structure and properties can be induced by a very small stimulus. Once that change occurs, there is no further change, meaning a predictable all-or-nothing response occurs, with complete uniformity throughout the polymer. Smart polymers may change conformation, adhesiveness or water retention properties, due to slight changes in pH, ionic strength, temperature, ultrasound, or other triggers. For example, Kubota et al designed and loaded ultrasound-responsive hydrogel microbeads with silica nanoparticles that were released under ultrasonic stimulation. [7]

Another factor in the effectiveness of smart polymers lies in the inherent nature of polymers in general. The strength of each molecule's response to changes in stimuli is the composite of changes of individual monomer units which, alone, would be weak. However, these weak responses, compounded hundreds or thousands of times, create a considerable force for driving biological processes.

The pharmacy industry has been directly related to the polymer’s advances. In this field, polymers are playing a significant role, and their advances are helping entire populations around the world. The human body is a machine with a complex system and works as a response to chemical signals. Polymers play the role of drug delivery technology that can control the release of therapeutic agents in periodic doses. [8] Polymers are capable of molecular recognition and directing intracellular delivery. [8] Smart polymers get into the field to play and take advantage of molecular recognition and finally produced awareness systems and polymer carriers to facilitate drug delivery in the body system.

Stimuli

Several polymer systems respond to temperature, undergoing a lower critical solution temperature phase transition. One of the better-studied such polymers is poly(N-isopropylacryamide), with a transition temperature of approximately 33 °C. Several homologous N-alkyl acrylamides also show LCST behavior, with the transition temperature depending on the length of the hydrophobic side chain. Above their transition temperature, these polymers become insoluble in water. This behavior is believed to be entropy driven.

Classification and chemistry

Currently, the most prevalent use for smart polymers in biomedicine is for specifically targeted drug delivery. Since the advent of timed-release pharmaceuticals, scientists have been faced with the problem of finding ways to deliver drugs to a particular site in the body without having them first degrade in the highly acidic stomach environment. Prevention of adverse effects on healthy bone and tissue is also an important consideration. Researchers have devised ways to use smart polymers to control the release of drugs until the delivery system has reached the desired target. This release is controlled by either a chemical or physiological trigger.

Linear and matrix smart polymers exist with a variety of properties depending on reactive functional groups and side chains. These groups might be responsive to pH, temperature, ionic strength, electric or magnetic fields, and light. Some polymers are reversibly cross-linked by noncovalent bonds that can break and reform depending on external conditions. Nanotechnology has been fundamental in the development of certain nanoparticle polymers such as dendrimers and fullerenes, that have been applied for drug delivery. Traditional drug encapsulation has been done using lactic acid polymers. More recent developments have seen the formation of lattice-like matrices that hold the drug of interest integrated or entrapped between the polymer strands.

Smart polymer matrices release drugs by a chemical or physiological structure-altering reaction, often a hydrolysis reaction resulting in cleavage of bonds and release of drug as the matrix breaks down into biodegradable components. The use of natural polymers has given way to artificially synthesized polymers such as polyanhydrides, polyesters, polyacrylic acids, poly(methyl methacrylates), poly(phthalaldehyde), and polyurethanes. Hydrophilic, amorphous, low-molecular-weight polymers containing heteroatoms (i.e., atoms other than carbon) have been found to degrade fastest. Scientists control the rate of drug delivery by varying these properties thus adjusting the rate of degradation.

A graft-and-block copolymer is two different polymers grafted together. A number of patents already exist for various combinations of polymers with different reactive groups. The product exhibits properties of both individual components which adds a new dimension to an intelligent polymer structure and may be useful for certain applications. Cross-linking hydrophobic and hydrophilic polymers result in the formation of micelle-like structures that can protectively assist drug delivery through aqueous medium until conditions at the target location cause the 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 (PAA). PAA adheres to mucosal surfaces but will swell and degrade rapidly at pH 7.4, resulting in the 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 to deliver and release 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 are 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 the 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 the 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 the production or release of insulin. Likewise, there are many possible applications of similar hydrogels as drug delivery agents for other conditions and diseases. [9]

Other Applications

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 the 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 the 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.

Smart polymers play an essential part in the technology of self-adaptive wound dressings. The dressing design presents proprietary super-absorbent synthetic smart polymers immobilized in the 3-dimensional fiber matrix with added hydration functionality achieved by embedding hydrogel into the core of the material.

The dressing's mode of action relies on the ability of the polymers to sense and adapt to the changing humidity and fluid content in all areas of the wound simultaneously and to automatically and reversibly switch from absorption to hydration. The smart polymer action ensures the active synchronized response of the dressing material to changes in and around the wound to support the optimal moist healing environment at all times. [5] [6]

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 toilets that analyze urine and help identify health problems. In environmental biotechnology, smart irrigation systems have been also 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.

See also

Related Research Articles

<span class="mw-page-title-main">Biopolymer</span> Polymer produced by a living organism

Biopolymers are natural polymers produced by the cells of living organisms. Like other polymers, biopolymers consist of monomeric units that are covalently bonded in chains to form larger molecules. There are three main classes of biopolymers, classified according to the monomers used and the structure of the biopolymer formed: polynucleotides, polypeptides, and polysaccharides. The Polynucleotides, RNA and DNA, are long polymers of nucleotides. Polypeptides include proteins and shorter polymers of amino acids; some major examples include collagen, actin, and fibrin. Polysaccharides are linear or branched chains of sugar carbohydrates; examples include starch, cellulose, and alginate. Other examples of biopolymers include natural rubbers, suberin and lignin, cutin and cutan, melanin, and polyhydroxyalkanoates (PHAs).

<span class="mw-page-title-main">Hydrogel</span> Soft water-rich polymer gel

A hydrogel is a biphasic material, a mixture of porous, permeable solids and at least 10% by weight or volume of interstitial fluid composed completely or mainly by water. In hydrogels the porous permeable solid is a water insoluble three dimensional network of natural or synthetic polymers and a fluid, having absorbed a large amount of water or biological fluids. These properties underpin several applications, especially in the biomedical area. Many hydrogels are synthetic, but some are derived from nature. The term 'hydrogel' was coined in 1894.

Smart materials, also called intelligent or responsive materials, are designed materials that have one or more properties that can be significantly changed in a controlled fashion by external stimuli, such as stress, moisture, electric or magnetic fields, light, temperature, pH, or chemical compounds. Smart materials are the basis of many applications, including sensors and actuators, or artificial muscles, particularly as electroactive polymers (EAPs).

<span class="mw-page-title-main">Alginic acid</span> Polysaccharide found in brown algae

Alginic acid, also called algin, is a naturally occurring, edible polysaccharide found in brown algae. It is hydrophilic and forms a viscous gum when hydrated. When the alginic acid binds with sodium and calcium ions, the resulting salts are known as alginates. Its colour ranges from white to yellowish-brown. It is sold in filamentous, granular, or powdered forms.

pH sensitive or pH responsive polymers are materials which will respond to the changes in the pH of the surrounding medium by varying their dimensions. Materials may swell, collapse, or change depending on the pH of their environment. This behavior is exhibited due to the presence of certain functional groups in the polymer chain. pH-sensitive materials can be either acidic or basic, responding to either basic or acidic pH values. These polymers can be designed with many different architectures for different applications. Key uses of pH sensitive polymers are controlled drug delivery systems, biomimetics, micromechanical systems, separation processes, and surface functionalization.

Thiolated polymers – designated thiomers – are functional polymers used in biotechnology product development with the intention to prolong mucosal drug residence time and to enhance absorption of drugs. The name thiomer was coined by Andreas Bernkop-Schnürch in 2000. Thiomers have thiol bearing side chains. Sulfhydryl ligands of low molecular mass are covalently bound to a polymeric backbone consisting of mainly biodegradable polymers, such as chitosan, hyaluronic acid, cellulose derivatives, pullulan, starch, gelatin, polyacrylates, cyclodextrins, or silicones.

Poly(N-isopropylacrylamide) (variously abbreviated PNIPA, PNIPAM, PNIPAAm, NIPA, PNIPAA or PNIPAm) is a temperature-responsive polymer that was first synthesized in the 1950s. It can be synthesized from N-isopropylacrylamide which is commercially available. It is synthesized via free-radical polymerization and is readily functionalized making it useful in a variety of applications.

A nanogel is a polymer-based, crosslinked hydrogel particle on the sub-micron scale. These complex networks of polymers present a unique opportunity in the field of drug delivery at the intersection of nanoparticles and hydrogel synthesis. Nanogels can be natural, synthetic, or a combination of the two and have a high degree of tunability in terms of their size, shape, surface functionalization, and degradation mechanisms. Given these inherent characteristics in addition to their biocompatibility and capacity to encapsulate small drugs and molecules, nanogels are a promising strategy to treat disease and dysfunction by serving as delivery vehicles capable of navigating across challenging physiological barriers within the body. 

<span class="mw-page-title-main">Self-healing hydrogels</span> Type of hydrogel

Self-healing hydrogels are a specialized type of polymer hydrogel. A hydrogel is a macromolecular polymer gel constructed of a network of crosslinked polymer chains. Hydrogels are synthesized from hydrophilic monomers by either chain or step growth, along with a functional crosslinker to promote network formation. A net-like structure along with void imperfections enhance the hydrogel's ability to absorb large amounts of water via hydrogen bonding. As a result, hydrogels, self-healing alike, develop characteristic firm yet elastic mechanical properties. Self-healing refers to the spontaneous formation of new bonds when old bonds are broken within a material. The structure of the hydrogel along with electrostatic attraction forces drive new bond formation through reconstructive covalent dangling side chain or non-covalent hydrogen bonding. These flesh-like properties have motivated the research and development of self-healing hydrogels in fields such as reconstructive tissue engineering as scaffolding, as well as use in passive and preventive applications.

Nanocomposite hydrogels are nanomaterial-filled, hydrated, polymeric networks that exhibit higher elasticity and strength relative to traditionally made hydrogels. A range of natural and synthetic polymers are used to design nanocomposite network. By controlling the interactions between nanoparticles and polymer chains, a range of physical, chemical, and biological properties can be engineered. The combination of organic (polymer) and inorganic (clay) structure gives these hydrogels improved physical, chemical, electrical, biological, and swelling/de-swelling properties that cannot be achieved by either material alone. Inspired by flexible biological tissues, researchers incorporate carbon-based, polymeric, ceramic and/or metallic nanomaterials to give these hydrogels superior characteristics like optical properties and stimulus-sensitivity which can potentially be very helpful to medical and mechanical fields.

<span class="mw-page-title-main">Edible packaging</span> Food containers which can be eaten

Edible packaging refers to packaging which is edible and biodegradable.

4-dimensional printing uses the same techniques of 3D printing through computer-programmed deposition of material in successive layers to create a three-dimensional object. However, in 4D printing, the resulting 3D shape is able to morph into different forms in response to environmental stimulus, with the 4th dimension being the time-dependent shape change after the printing. It is therefore a type of programmable matter, wherein after the fabrication process, the printed product reacts with parameters within the environment and changes its form accordingly.

Hydrogels are three-dimensional networks consisting of chemically or physically cross-linked hydrophilic polymers. The insoluble hydrophilic structures absorb polar wound exudates and allow oxygen diffusion at the wound bed to accelerate healing. Hydrogel dressings can be designed to prevent bacterial infection, retain moisture, promote optimum adhesion to tissues, and satisfy the basic requirements of biocompatibility. Hydrogel dressings can also be designed to respond to changes in the microenvironment at the wound bed. Hydrogel dressings should promote an appropriate microenvironment for angiogenesis, recruitment of fibroblasts, and cellular proliferation.

<span class="mw-page-title-main">Dextran drug delivery systems</span> Polymeric drug carrier

Dextran drug delivery systems involve the use of the natural glucose polymer dextran in applications as a prodrug, nanoparticle, microsphere, micelle, and hydrogel drug carrier in the field of targeted and controlled drug delivery. According to several in vitro and animal research studies, dextran carriers reduce off-site toxicity and improve local drug concentration at the target tissue site. This technology has significant implications as a potential strategy for delivering therapeutics to treat cancer, cardiovascular diseases, pulmonary diseases, bone diseases, liver diseases, colonic diseases, infections, and HIV.

Conventional drug delivery is limited by the inability to control dosing, target specific sites, and achieve targeted permeability. Traditional methods of delivering therapeutics to the body experience challenges in achieving and maintaining maximum therapeutic effect while avoiding the effects of drug toxicity. Many drugs that are delivered orally or parenterally do not include mechanisms for sustained release, and as a result they require higher and more frequent dosing to achieve any therapeutic effect for the patient. As a result, the field of drug delivery systems developed into a large focus area for pharmaceutical research to address these limitations and improve quality of care for patients. Within the broad field of drug delivery, the development of stimuli-responsive drug delivery systems has created the ability to tune drug delivery systems to achieve more controlled dosing and targeted specificity based on material response to exogenous and endogenous stimuli.

<span class="mw-page-title-main">Gated drug delivery systems</span> Method of controlled drug release

Gated drug delivery systems are a method of controlled drug release that center around the use of physical molecules that cover the pores of drug carriers until triggered for removal by an external stimulus. Gated drug delivery systems are a recent innovation in the field of drug delivery and pose as a promising candidate for future drug delivery systems that are effective at targeting certain sites without having leakages or off target effects in normal tissues. This new technology has the potential to be used in a variety of tissues over a wide range of disease states and has the added benefit of protecting healthy tissues and reducing systemic side effects.

Pullulan bioconjugates are systems that use pullulan as a scaffold to attach biological materials to, such as drugs. These systems can be used to enhance the delivery of drugs to specific environments or the mechanism of delivery. These systems can be used in order to deliver drugs in response to stimuli, create a more controlled and sustained release, and provide a more targeted delivery of certain drugs.

pH-responsive tumor-targeted drug delivery is a specialized form of targeted drug delivery that utilizes nanoparticles to deliver therapeutic drugs directly to cancerous tumor tissue while minimizing its interaction with healthy tissue. Scientists have used drug delivery as a way to modify the pharmacokinetics and targeted action of a drug by combining it with various excipients, drug carriers, and medical devices. These drug delivery systems have been created to react to the pH environment of diseased or cancerous tissues, triggering structural and chemical changes within the drug delivery system. This form of targeted drug delivery is to localize drug delivery, prolongs the drug's effect, and protect the drug from being broken down or eliminated by the body before it reaches the tumor.

Bioprinting drug delivery is a method for producing drug delivery vehicles. It uses three-dimensional printing of biomaterials via additive manufacturing. Such vehicles are biocompatible, tissue-specific hydrogels or implantable devices. 3D bioprinting prints cells and biological molecules to form tissues, organs, or biological materials in a scaffold-free manner that mimics living human tissue. The technique allows targeted disease treatments with scalable and complex geometry.

Ultrasound-triggered drug delivery using stimuli-responsive hydrogels refers to the process of using ultrasound energy for inducing drug release from hydrogels that are sensitive to acoustic stimuli. This method of approach is one of many stimuli-responsive drug delivery-based systems that has gained traction in recent years due to its demonstration of localization and specificity of disease treatment. Although recent developments in this field highlight its potential in treating certain diseases such as COVID-19, there remain many major challenges that need to be addressed and overcome before more related biomedical applications are clinically translated into standard of care.

References

  1. ↑ M.Shahinpoor and H.-J. Schneider, Eds. Intelligent Materials; Royal Society of Chemistry, Cambridge UK, 2007
  2. ↑ M. Schwartz, Ed. Smart Materials, CRC Press Boca Raton 2008
  3. ↑ Intelligent Materials, Editors: Mohsen, Shahinpoor, Hans-Jörg Schneider Royal Society of Chemistry Cambridge 2007
  4. ↑ Galaev, Igor; Mattiasson, Bo, eds. (2010). Smart Polymers: Applications in Biotechnology and Biomedicine. CRC Press. ISBN   978-1439858165 . Retrieved 2013-03-20.
  5. 1 2 Wolcott, R.; Fischenich, V. (2014). "Ultimate Standardization of First-Line Wound Dressings to a Single Type". Today's Wound Clinic. 8 (3).
  6. 1 2 USpatent US9050211 B2,Oleg Siniaguine&Elena Kachiguina,"Self-adaptive and optionally also otherwise adaptable wound dressing",published 2015-06-09
  7. ↑ Kubota, Takeshi; Kurashina, Yuta; Zhao, JianYi; Ando, Keita; Onoe, Hiroaki (2021-05-01). "Ultrasound-triggered on-demand drug delivery using hydrogel microbeads with release enhancer". Materials & Design. 203: 109580. doi: 10.1016/j.matdes.2021.109580 . ISSN   0264-1275. S2CID   233958432.
  8. 1 2 Liechty, W. B., Kryscio, D. R., Slaughter, B. V., & Peppas, N. A. (2012). Polymers for drug delivery systems. HHS Author Manuscripts. Journal List. PMC.
  9. ↑ Bordbar-Khiabani A, Gasik M. "Smart hydrogels for advanced drug delivery systems". International Journal of Molecular Sciences. 23 (7): 3665. doi: 10.3390/ijms23073665 .
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