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Review

Inclusion and Functionalization of Polymers with Cyclodextrins: Current Applications and Future Prospects

by
Christian Folch-Cano
1,*,
Mehrdad Yazdani-Pedram
1 and
Claudio Olea-Azar
2,*
1
Departamento de Química Orgánica y Fisicoquímica, Universidad de Chile, Sergio Livingstone 1007, P.O. Box 233, Independencia, Santiago 8380492, Chile
2
Departamento de Química Inorgánica y Analítica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Casilla 233, Santiago 8380492, Chile
*
Authors to whom correspondence should be addressed.
Molecules 2014, 19(9), 14066-14079; https://doi.org/10.3390/molecules190914066
Submission received: 18 July 2014 / Revised: 27 August 2014 / Accepted: 2 September 2014 / Published: 9 September 2014
(This article belongs to the Special Issue Supramolecular Devices from Cyclodextrin: Synthesis and Pharmacological Applications)
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Abstract

:
The numerous hydroxyl groups available in cyclodextrins are active sites that can form different types of linkages. They can be crosslinked with one another, or they can be derivatized to produce monomers that can form linear or branched networks. Moreover, they can form inclusion complexes with polymers and different substrates, modifying their physicochemical properties. This review shows the different applications using polymers with cyclodextrins, either by forming inclusion complexes, ternary complexes, networks, or molecularly imprinted polymers (MIPs). On one hand, the use of cyclodextrins enhances the properties of each polymer, and on the other the use of polymers decreases the amount of cyclodextrins required in different formulations. Both cyclodextrins and polymers contribute synergistically in several applications such as pharmacological, nutritional, environmental, and other industrial fields. The use of polymers based on cyclodextrins is a low cost easy to use potential tool with great future prospects.

Graphical Abstract

1. Introduction

Cyclodextrins (CDs) are cyclic oligosaccharides composed of glucose units connected by α-1,4-glycosidic linkages with numerous available hydroxyl groups that are active sites for forming different types of derivatives and linkages. They are truncated-cone-shaped, with a relatively hydrophobic cavity and an external hydrophilic surface, capable of forming inclusion complexes (ICs) with various molecules, by incorporating them into the cavity [1,2,3]. The formation of ICs can modify the physical, chemical, and biological properties of the guest molecule, expanding its application field. The ability of a CD to form an IC with a guest molecule is a function of steric as well as thermodynamic factors. The driving forces for complex formation are attributed to the removal of water molecules from the hydrophobic cavity and the formation of Van der Waals, hydrophobic, and hydrogen bond interactions [4,5]. CDs have been recommended for applications in food processing and as food additives with various aims, like protecting lipophilic food components that are oxidizable and degradable by light or heat, solubilizing vitamins and dyes, encapsulating flavours, fragances, and essential oils against unwanted changes, suppressing unpleasant odors or tastes; and achieving controlled release of certain food and drug constituents [6,7,8,9].
CDs have been found to form ICs not only with low molecular weight compounds. New molecular structures and functions have been obtained by the inclusion of polymer chains in the cavities of CDs [10]. Figure 1 shows a schematic representation of some IC between them. Solid state NMR spectroscopy is an efficient technique to study the conformations and molecular motions of polymer inclusion complexes. Lu et al. [11] studied the conformations and dynamics of series of crystalline polymers. The ICs obtained showed single chains for urea and perhydrotriphenylene with α-CD and double chains for poly(ethylene oxide) and poly(ϵ-caprolactone) with γ-CD channels, like the double stranded occupancy of poly(ethylene glycol)-γ-CD IC exposed by Harada et al. [12]
Molecules 19 14066 g001 550
Figure 1. Schematic representation of linear complexation of a polymer chain by CDs and CDs derived with monomeric fractions forming a ring type arrangement.
Figure 1. Schematic representation of linear complexation of a polymer chain by CDs and CDs derived with monomeric fractions forming a ring type arrangement.
Molecules 19 14066 g001
In this review we will show the different applications made possible by the use of polymers with cyclodextrins, either by forming inclusion complexes, ternary complexes, networks and molecularly imprinted polymers (MIPs). On one hand, the use of cyclodextrins enhances the properties of each polymer, and on the other the use of polymers decreases the amount of cyclodextrins necessary in different formulations. Both cyclodextrins and polymers contribute synergistically in several applications such as in the pharmacological, nutritional, environmental and general industrial fields, making the use of polymers based on cyclodextrins a low cost, easy to use potential tool with great future prospects.

2. Polymers as Ternary Complex Constituents

The encapsulating properties of CDs can be improved by forming ternary complexes. The ternary complexes are supramolecular systems composed of three distinct molecular entities. From this point of view, this ternary system would be represented by an auxiliary substance which, in conjunction with CD, can improve the physicochemical, chemical and bioavailability properties of a guest molecule. Depending on the case, the use of a third component improves encapsulation or release and reduces the amount of CD needed to obtain the benefits mentioned above. In this way can optimize the cost, toxicity, and bulk formulation of the desired product.
Polymers are the most widely used ternary components in drug/CD systems [9]. Faucci et al. [13] studied the effect of water soluble polymers like sodium carboxymethylcellulose, hydroxylpropyl-methylcellulose, polyvinylpyrrolidone K30, and polyethylene glycol 6000 on naproxen solubility improvement. The combined use of polymer and CD was always clearly more effective in enhancing the aqueous solubility of naproxen compared to the corresponding drug/polymer or drug/CD binary systems. The solubilization enhancement was not simply additive, but synergistic. Their addition leads to decreased drug cristallinity and synergetic effects on the solubilizing action of CDs. For example, in polyvinylpyrrolidone/CD/drug systems, an increase in the solubility of the drugs was experienced under the polymer's effect. However, the increase in the solubility was not greater than for other polymers like hydroxypropylmethylcellulose or plasdone [1].

3. Networks of Polymers and Cyclodextrins

The first approaches to the potential applications of cyclodextrin polymers (soluble and insoluble) in the pharmaceutical industry were reviewed by Fenivesy [14] and Szeman et al. [15] These authors studied the complex-forming ability of a water-soluble β-CD epichlorohydrin, a polymer that formed quite soluble inclusion compounds with some drugs. Renard et al. [16] established that the molar weight of these water soluble polymers depends on initial features like initial ratio (epichlorohydrin/β-CD), NaOH concentration, and reaction time. They indicated that low concentrations of NaOH promote substitution on the two sides of the CD cavity, while high NaOH concentrations result in substitution mainly on one side of the cavity.
There are several procedures for the conversion of β-CD into derivatives capable of interacting with compounds from aqueous solutions, and the methods can be classified in two ways. The first method involves the direct modification of β-CD by cross-linking, which consists in the bonding of the molecules to each other, by concatenation through a coupling agent, to form an insoluble three-dimensional network, as schematized in Figure 2. The properties can be adjusted according to the type of CD, the cross-linking spacer, or the molar ratio between the two, getting materials with different characteristics in terms of density, surface area, pore structure, chemical properties, and sorption behavior.
Molecules 19 14066 g002 550
Figure 2. Scheme of different polymer-based CD networks.
Figure 2. Scheme of different polymer-based CD networks.
Molecules 19 14066 g002
Covalent polymer networks containing cyclodextrins are of great interest because their croslinked macromolecular structure has a cooperative action between the cyclodextrin cavities, or between the cavities and the polymeric network, in the complexation and adsorption of water soluble components. From this perspective, CD polymers were prepared by solubilization of citric acid as crosslinking agent and sodium hypophosphite as catalyst [17,18], and they were used to improve the complexation of some drugs. These polymers with an anionic character present low toxicity and an environmentally friendly composition.
The second method is based on the covalent binding of β-CD molecules to a pre-existing insoluble matrix such as highly cross-linked synthetic polymers. This kind of CD immobilization on insoluble supports can be regarded as an appropriate way to get insoluble CD materials with specific properties like functional delivery additives or to act as sensors or filters [19]. The hydroxyl groups of CDs have been successfully functionalized with vinyl groups by reacting with acryloyl chloride to produce an ester. Homo- and copolymerization of this modified CD monomer are being explored using free radical initiators. Comonomers such as t-butyl acrylate, methyl methacrylate and styrene are being used, since their side groups confer solubility in common solvents. The CD content of the copolymer can be controlled by varying the comonomer content [20]. Munteanu et al. [21] synthesized such polymerizable CD monomers via a “click chemistry” route leading to a ring-like supramolecular structure. Copper(I)-catalyzed Huisgen type 1,3-dipolar cycloadition of azides and alkynes extended its area of application. By applying a click reaction, CD monomethacrylate can be obtained in high yields; purification by chromatographic methods is not required, and installation and removal of protecting groups is avoided. The triazol linker is relatively stable toward cleavage, oxidation, or reduction. Click reactions as a possibility to obtain polymer chains with covalently attached CDs and examples of the application of such polymers in drug delivery have been reported [22].
Doyagües et al. [23] reported the synthesis and aqueous catalytic evaluation of a linear copolymer bearing both pendant proline and permethylated β-CD groups. They showed the synthesis of the protected hydroxyproline methacrylate and permethylated 6-azido-6-deoxy-β-cyclodextrin used as a precursor of styrenic compounds. The copolymer was designed on the basis that the presence of the hydrophobic cavity of the β-CD could bring aromatic substrates into close proximity of the surrounding catalytic proline residues through host−guest interactions. The compound is water-soluble and catalyzes aldol reactions in this medium without the need for any extra organic solvent. The copolymeric catalyst showed a pH-dependent behavior. At pH 7.0 the copolymer is found as extended single chains with negative charge, catalyzing the reaction in a fast and nonstereoselective mode. On the other hand, at pH 3.8 it is forming charge complexes, multichain hydrophobic nanoaggregates that have probably been stabilized by the permethylated-β-CD presence.
Based on the background outlined above, the click reaction allows synthesizing monomers of some polymers functionalized with permethylathed-β-CD. Moreover, this monomer can be copolymerized by a bottom-up route. Moers et al. [24] synthesized monoadamantyl-functional hyperbranched and linear–hyperbranched polyglycerols by a self-assembly process. Polymers with molecular weights ranging from 2700 to 12,100 g/mol were obtained. The association constant was found to drop with increasing molecular weight of the hyperbranched polyglycerol, but it levels off to a final value already at moderate molecular weights of the hyperbranched block. Additionally, the presence of the polyethylene glycol spacer between the adamantyl group and the hyperbranched polyglycerol resulted in significantly increased association constants, demonstrating the steric effect of branching.
Another alternative is the simple and well-known chemical crosslinking reaction using epichlorohydrin as cross-linker. This cross-linker contains two reactive functional groups that can form bonds with CD molecules and/or itself. The resulting polymers are mixtures containing CD units joined by repeating glyceryl linkers. A number of CDs are interconnected and a three-dimensional (co)polymer network is formed. These (co)polymers are called gels or hydrogels due to their highly hydrophilic nature. A large number of papers have been published on the synthesis and use of these gels, and they have been reviewed by Crini et al. [19].
The epichlorohydrin-β-CD polymers were used by Zhao et al. [25] to prepare a novel β-CD polymer/tungsten carbide (CroCD-TuC), comparing it with Sephadex G15 beads in terms of their adsorbing capacity for rutin [26]. They concluded that its adsorption isotherms (Langmuir adsorption equation) and adsorption capacity are gradually reduced as the solution's temperature and pH rise, but it increases with increasing solvent polarity. Thermodynamic studies revealed that the formation of the rutin-β-CD complex CroCD-TuC skeleton showed significant contribution to the adsorption compared to Sephadex. In a modified interfacial polymerization, nylon-6,10 containing various amounts of covalently bonded dimethyl-βCD has been obtained by Tonelli [27].
These dimethyl-β-CD-nylon-6,10 polymers showed thermal degradation characteristics very similar to pure nylon-6,10, and they are more readily dyed at higher dye levels than pure nylon-6,10 due to the β-CD effect.

4. Molecularly Imprinted Polymers (MIPs) with Cyclodextrins

In order to increase the adsorption selectivity of some polymers, molecularly imprinted molecules have been designed. Their application is mainly oriented at the recognition of target molecules in biological systems such as artificial receptors, and also in analytical separation processes. In the gest-binding sites it is likely that CDs are arranged complementarily to the template in the polymer. To immobilize and determine the position of CD residues in the polymer, two or more hydrophobic molecules that can form ICs with CDs should be fixed in the template (Figure 3).
Molecules 19 14066 g003 550
Figure 3. Schematic representation of a hydrophobic template molecule in a CD-based MIP.
Figure 3. Schematic representation of a hydrophobic template molecule in a CD-based MIP.
Molecules 19 14066 g003
Asanuma et al. [28,29] synthesized acryloyl-CDs as functional vinyl monomers, and various antibiotics and oligopeptides were molecularly-imprinted to them in water. They proposed that the imprinting effect is eminent when the template involved more than two hydrophobic residues on a rigid molecular frame promoting guest selectivity including enantioselectivity.
Egawa et al. [30] prepared microspheres of molecular imprinted CDs in a dimethylsulfoxide/poly(dimethylsiloxane) emulsion, using cholesterol and other steroids as template molecules. Cholesterol-specific binding ability into the MIP was most remarkable and they proposed it as a novel cholesterol selective MIP.
The high selectivity of CDs based on MIP was corroborated by Guo et al. [31], who reported a novel approach for preparing a MIP with CD pseudo-polyrotaxanes as pseudo-supports, which are formed by self-assembling assistant recognition polymer chains with γ-CD. For these purposes, template bovine serum albumin (BSA) was first selectively assembled with modified CD pseudo-polyrotaxanes to form IC in the presence of Cu ions. The MIP was characterized by 2D-NOESY, thermogravimetric analysis (TGA), and wide-angle X-ray diffraction (WARD). Other β-CD-based MIPs were synthesized using β-CD as monomer that is cross-linked by toluene-2,4-diisocyanate with different template molecules. Kyzas et al. [32] prepared MIPs using Remazol Red 3BS (RR) as template molecule. The selectivity of the MIP was elucidated in a trichromatic dye solution. Its regeneration/reuse capability was dependent on pH. The CD-MIPs showed higher rebinding of dye than chitosan MIPs prepared in the study. N-phenyl-1-naphthylamine was also used as template molecule by Ng et al. [33], showing better sensing signal by increasing the binding affinity and substrate-selectivity towards the template molecule compared with the control polymer prepared in its absence. Another template used for this type of MIP was dextromethorphan, which is an important pharmacological marker drug used to identify the activity of the CYP2D6 class of p450 monooxygenases [34]. Detection and quantification were made by measuring the refractive index changes of multiple surface plasmons resulting from the binding of imprinted βCD polymer in pockets.
On the other hand, β-CD was also used as a monomer cross-linked with epichlorohydrin in the presence of creatinine, which was a template for the imprinting [35]. N-hydroxysuccinimide and 2-pyrrolinidone were used as creatinine analogues in the adsorption of multi-component solutions to reveal the specific recognition ability of the abovementioned MIP for the creatinine template molecule. The specific binding of the creatinine-MIP was confirmed. The adsorption resulting from the solution mixture by MIP showed superior binding effect for the target molecule, creatinine, rather than creatine, N-hydroxysuccinimide, and 2-pyrrolinidone.
A novel photonic MIP was designed for amino acid sensing using maleic anhydride-modified β-CD and acrylic acid as functional monomers [36]. This β-CD-based MIP could undergo a swelling change from 590 nm to 704 nm and still retain the molecular imprinting recognition ability during the sensing of l-phenylalanine. The authors proposed it as a sensor to detect l-phenylalanine in compound amino acid injection samples due to this high specificity with respect to d-phenylalanine, l-tyrosine, and l-tryptophan.

5. Current Applications of Polymers and CD Networks

Because CDs are nontoxic, biodegradable and bioabsorbable, they may be used in polymeric networks for varied purposes oriented mainly at applications like food, environmental for removing organic pollutants and heavy metal ions from water, and pharmacological, as listed in Table 1.
Table
Table 1. Reported applications of some CD-polymeric networks.
Table 1. Reported applications of some CD-polymeric networks.
PolymerApplicationRef.
β- and γ-CDs linked with chitosanBitter-masking of caffeine solutions and bitter natural extracts[37]
β-CD with one of the following crosslinking agents: epichlorohydrin, diphenyl carbonate, or hexamethylene diisocyanate and propargyl-β-CD with 1,3-bis(azidomethyl) benzeneDebittering agents by adsorption of narangin, limonin and caffeine[38]
β-CD and epichlorohydrinEnvironmental purposes: detoxification of wastewater, color removal, concentration and purification of solutions[19]
Delivery of Lavandula angustifolia essential oil used as ambient odors[39]
Retention of aroma compounds of Mentha piperita esential oil[40]
Adsorption of pesticides from water[41]
Removal of Cu2+ from aqueous solutionss[42]
β-CD and anionic and cationic acrylamideEnhancement of oil recovery[22]
Chemically cross-linked and grafted cyclodextrinsDrug release from hydrogels[28]
α-, β- and γ-CDs functionalized with acrylic groupsAqueous nanogels[43]
β-CD polymer/tungsten carbideAdsorption of rutin[26]
β-CD, acrylic acid, N,N'-methylenebisacrylamideHydrogel for the removal of heavy metal ions[44]
Monomethacrylated β-CD copolymerized with N-isopropylacrylamideDrug delivery[21]
Oligosaccharide γ-CD with dibasic acid dichloridesAdsorption of polychlorobiphenyl contaminants in oil[45]
β-CD-citric acidDrug delivery of ciprofloxacin (an antibiotic) and prednisolone (an anti-inflammatory drug)[46]
β-CD-dextran polymersDrug delivery[47]
HPγ-CD polymer and sulfobutylether-β-CD with epichlorohydrinAdsorption of ionizable oxytetracycline antibiotics[48]
Phosphorous-containing β-CD polymers1-adamantyl acetic acid, or with divalent cations, such as Ca2+[49]
CD crosslinked with 4,4'-methylenebis(phenyl isocyanate)Removal of patulin from apple juice[50]
Glycidyl methacrylate alone or in combination with β-CDIncorporation of insecticide in cotton textiles[51]
α-CD-polymer gels with various poly(ethylene oxide) (PEO)-based copolymersDelivery of vancomycin for the treatment of bone infections[52]
From β-CD and sulfobutylether-β-CD with epichlorohydrinSolubilization of repaglinide (hypoglycemic agent)[53]
β-CD-ionic liquid polymer with 1-benzylimidazole and crosslinked using toluenediisocyanateSorption capacity and high removal towards phenols and arsenic(V)[54]
Carboxymethyl-hydroxypropyl-β-CD polymer-modified Fe3O4 magnetic particles (CM-HP-β-CDCP-MNPs)Magnetic solid phase extraction of rutin[55]
Crosslinked polyvinyl alcohol/glutaraldehyde (PVA/GA) membranes with β-CDTextile liquid waste processing[56]
PCCA thin film modified with β-CD polymerCapping cavity for the selective detection of paraoxon-ethyl and parathion-ethyl chemical agents[57]
Cyclodextrin-based polymers have been shown to be efficient drug delivery materials; βCD-citric acid in-situ polymerization was used to functionalize two kinds of porous silicon (nanoporous and macroporous) that were used as matrices for drug release studies either in water or phosphate buffer solutions using ciprofloxacin and prednisolone as model drugs. Both cyclodextrin-based polymer composites showed better release control for drug delivery applications than non-functionalized silicon-β-CD-citric acid composite [46]. The drug delivery for eventual parenteral administration of poorly soluble drugs was also studied by using novel β-CD-dextran polymers [47]. In this study the size distribution of β-CD-dextrans and the influence of dextran backbones on the stability of the β-CD/drug complex as well as the solubilization efficiency were investigated. The stability of the β-CD/drug complex was not affected by the dextran backbone compared to native and commercially available β-CD derivatives. It was concluded that these new polymers have higher drug solubilization capacity compared to commercially available β-CDs.
Supramolecular gels showed good cytocompatibility against SAOS-2 cells and in the HET-CAM test [52]. The supramolecular gels of α-cyclodextrin-polymer with various poly(ethylene oxide) (PEO)-based water-soluble copolymers were synthesized from α-CD by crosslinking with epichlorohydrin in alkaline medium and they were able to sustain the release of vancomycin for at least 5 days at 37 °C, more efficiently than dispersions of either polymer component separately, resulting in a potential controlled delivery system for the treatment of bone infections.
Cross-linked CD-based nanosponges, from β-CD and sulfobutylether-β-CD with epichlorohydrin were synthesized [53]. The complexing properties of the polymers were investigated against repaglinide (a hypoglycemic agent, practically insoluble in water), providing higher solubilization ability. The amount of dissolved repaglinide is almost twice the amount dissolved in the presence of CD monomers. They proposed that the lower solubilization effect of SBEβ-CD-NS is probably due to steric hindrance, though its loading capacity is significantly higher.
From an environmental perspective, the spherical porous CD polymers prepared with one-fold or composite CDs as complexing agents and epichlorohydrin as cross-linking reagent were studied in terms of the relationship between adsorption potential and adsorbent-adsorbate, and their ability to adsorb and separate pesticides from water [41] was investigated by environmental adsorbent design, studying the effects of pH on adsorption and removal efficiency of ionizable organic compounds [48]. In the latter study, the authors checked the pH-dependent adsorption of the ionizable antibiotic oxytetracycline (comprising OTCH2+, OTCH±, OTC−, and OTC2−) on cyclodextrin polymers from the standpoint of molecular recognition and pH inertness. Based on these findings, they proposed HPγ-CD polymers to adsorb and remove oxytetracycline at pH 5.0 and 7.0, showing high removal efficiency and strong resistance to the interference of coexisting components.
Kawano et al. [45] cross-linked the renewable cyclic oligosaccharide γ-CD with dibasic acid dichlorides, as a new selective and powerful adsorbent to remove polychlorobiphenyl contaminants from oil (with >99.9% recovery efficiency) by simply washing with acetone.
The adsorption-desorption trends of epichlorohydrin cross-linked with β-CD, along with its good recyclability, establish an alternative, effective, and novel remediation technology for the removal of Cu2+ from aqueous solutions. The adsorption of Cu2+ was observed to be higher at pH 6.0 and showed a pseudo-second-order kinetic model. The maximum binding of Cu2+ was estimated to be 111.11 mg/g through the Langmuir isotherm model—much higher than that of existing sorption technologies [42].
From an electrochemical perspective, Zhang et al. [58] functionalized carbon nanomaterials modified with β-CD polymers that been bonded by non-covalent interactions. They prepared electrodes modified with the nanomaterials that exhibited high electrochemical performance with high supramolecular recognition properties.
Novel phosphorous-containing β-CD polymers with molecular weights higher than 104 g·mol−1 were synthesized by polycondensation between the hydroxyl groups of β-CD and non-toxic sodium trimetaphosphate under “green chemistry” conditions. These were non-reticulated and soluble CDs. Strong interactions with probes such as 1-adamantyl acetic acid or with divalent cations such as Ca2+ were observed. This was attributed to the presence of β-CD and phosphate groups in the polymer. The phosphated compounds obtained also displayed high affinity towards hydroxyapatite, leading to a quantitative determination of the total amount of phosphate molecules fixed on hydroxyapatite [49].
Β-CD-ionic liquid polymer (CD-ILP) was first synthesized by β-CD functionalized with 1-benzylimidazole (BIM) to form monofunctionalized CD (β-CD-BIMOTs), and it was further polymerized using a toluene diisocyanate linker to form insoluble CD-ILP (β-CD-BIMOTs-TDI) [54]. The presence of ionic liquid (IL) increases pore size, while the thermogravimetric analysis result showed that the presence of IL increases the stability of the polymer. The authors showed that the β-CD-BIMOTs-TDI polymer presents enhanced sorption capacity and high removal of phenols and arsenic(V).
Carboxymethyl-hydroxypropyl-β-CD polymer-modified Fe3O4 magnetic particles (CM-HP-β-CDCP-MNPs) were prepared and applied to magnetic solid phase extraction of rutin combined with UV–visible spectrometric detection [55]. The maximum adsorption capacity was high for rutin, with short equilibrium time and the possibility of reusing the adsorbent up to ten times.
Another applied perspective shows the study of Shirasawa et al. [50], who used a CD-based polymer for patulin analysis in apples. An insoluble polymer composed of cyclodextrin crosslinked with 4,4'-methylenebis(phenylisocyanate) was synthesized for use in the solid phase extraction of patulin from apple juice.
In an innovative perspective, cotton textiles which act against insects such as mosquitoes were designed by the incorporation of efficient insecticides (permethrin, bioallethrin) in the macro-molecular structure of cotton fabrics modified by grafting. The grafting reaction was carried out with glycidyl methacrylate or combinated with β-CD by irradiation using fast electron beams [51]. The amount of insecticide incorporated in the grafted cotton fabrics was increased by increasing the amount of β-CD. These grafted cotton fabrics showed fast action against mosquitoes.
The ability of cyclodextrin to include a wide variety of chemicals was also exploited for dye adsorption to show the potentialities of the membranes in textile liquid waste processing [56]. Adsorption of reactive methyl orange and methylene blue dyes on crosslinked polyvinyl alcohol/glutaraldehyde (PVA/GA) membranes was carried out, and attempts to obtain hydrophilic crosslinked PVA membranes were made by adding various amounts of β-CD. The membranes were consequently studied using UV-Vis spectroscopy at wavelengths of 547, 463, and 660 nm. The authors indicated that there is no covalent bond formation between PVA and β-CD; the β-CD is completely mixed into the PVA matrix polymer. The adsorption capacity increases with increasing amounts of cyclodextrin and the change in adsorption capacity may be due to the dye structure effect, and the negative free energy indicated the spontaneous nature of adsorption.
An optical chemical sensor for the detection of organophosphate (OP) compounds using a polymerized crystalline colloidal array (PCCA) thin film composed of a close-packed colloidal array of polystyrene particles was developed [57]. The PCCA thin film was modified with β-CD polymer as a capping cavity for the selective detection of paraoxon-ethyl and parathion-ethyl chemical agents. A fast response time (10 s) and high sensitivity with detection limits of 2.0 and 3.4 ppb for the abovementioned compounds were established by the authors.

6. Conclusions

The encapsulating characteristics of cyclodextrins, accompanied by the ease with which they can be derivatized, allows the formation of inclusion complexes with various polymers, with the possibility of crosslinking them as well as of forming monomers, which can then be part of polymeric networks, with synergistic properties that can enhance the properties of both the cyclodextrins and the polymers, leading to the modification of the physicochemical properties of some adsorbates or guest molecules. Currently, these cyclodextrin-based polymers are used mainly in drug delivery processes, gel design, encapsulation of specific molecules in food matrices, environmental applications, and in the creation of new textile products, among others. Additionally, new applications focused on increasing the selectivity properties, oriented at biochemical processes, are currently being addressed through the design and use of molecularly imprinted polymers containing cyclodextrins. The design and use of the properties of polymers and cyclodextrins, the wide range of existing studies and their potential applications are undoubtedly the starting point of much future research.

Acknowledgments

This work was supported by FONDECYT Postdoctoral Project 3120232.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Kurkov, S.V.; Loftsson, T. Cyclodextrins. Int. J. Pharm. 2013, 453, 167–180. [Google Scholar] [CrossRef]
  2. Brewster, M.E.; Loftsson, T. Cyclodextrins as pharmaceutical solubilizers. Adv. Drug Deliv. Rev. 2007, 59, 645–666. [Google Scholar]
  3. Del Valle, E.M.M. Cyclodextrins and their uses: A review. Process Biochem. 2004, 39, 1033–1046. [Google Scholar]
  4. Acuña-Rougier, C.; Olea-Azar, C. Thermodynamic and geometric study of diasteroisomeric complexes formed by racemic flavanones and three cyclodextrins through NMR. J. Incl. Phenom. Macrocycl. Chem. 2013, 75, 119–136. [Google Scholar] [CrossRef]
  5. Rekharsky, M.V.; Inoue, Y. Complexation thermodynamics of cyclodextrins. Chem. Rev. 1998, 98, 1875–1918. [Google Scholar]
  6. Astray, G.; Gonzalez-Barreiro, C.; Mejuto, J.C.; Rial-Otero, R.; Simal-Gándara, J. A review on the use of cyclodextrins in foods. Food Hydrocolloid 2009, 23, 1631–1640. [Google Scholar] [CrossRef]
  7. Szente, L.; Szejtli, J. Cyclodextrins as food ingredients. Trends Food Sci. Technol. 2004, 15, 137–142. [Google Scholar] [CrossRef]
  8. Szejtli, J.; Szente, L. Elimination of bitter, disgusting tastes of drugs and foods by cyclodextrins. Eur. J. Pharm. Biopharm. 2005, 61, 115–125. [Google Scholar] [CrossRef]
  9. Loftsson, T.; Brewster, M.; Másson, M. Role of cyclodextrins in improving oral drug delivery. Am. J. Drug. Deliv. 2004, 2, 261–275. [Google Scholar] [CrossRef]
  10. Harada, A. Construction of supramolecular structures from cyclodextrins, polymers. Carbohyd. Polym. 1997, 34, 183–188. [Google Scholar] [CrossRef]
  11. Lu, J.; Mirau, P.A.; Tonelli, A.E. Chain conformations and dynamics of crystalline polymers as observed in their inclusion compounds by solid-state NMR. Prog. Polym. Sci. 2002, 27, 357–401. [Google Scholar] [CrossRef]
  12. Harada, A.; Li, J.; Kamachi, M. Double-stranded inclusion complexes of cyclodextrin threaded on poly(ethylene glycol). Nature 1994, 370, 126–128. [Google Scholar] [CrossRef]
  13. Faucci, M.T.; Mura, P. Effect of water-soluble polymers on naproxen complexation with natural and chemically modified beta-cyclodextrins. Drug Dev. Ind. Pharm. 2001, 27, 909–917. [Google Scholar]
  14. Fenyvesi, É. Cyclodextrin polymers in the pharmaceutical industry. J. Incl. Phenom. 1988, 6, 537–545. [Google Scholar] [CrossRef]
  15. Szeman, J.; Fenyvesi, E.; Szejtli, J.; Ueda, H.; Machida, Y.; Nagai, T. Water soluble cyclodextrin polymers: Their interaction with drugs. J. Incl. Phenom. 1987, 5, 427–431. [Google Scholar] [CrossRef]
  16. Renard, E.; Deratani, A.; Volet, G.; Sebille, B. Preparation and characterization of water soluble high molecular weight β-cyclodextrin-epichlorohydrin polymers. Eur. Polym. J. 1997, 33, 49–57. [Google Scholar] [CrossRef]
  17. Danel, C.; Azaroual, N.; Chavaria, C.; Odou, P.; Martel, B.; Vaccher, C. Comparative study of the complex forming ability and enantioselectivity of cyclodextrin polymers by CE and 1H-NMR. Carbohyd. Polym. 2013, 92, 2282–2292. [Google Scholar] [CrossRef]
  18. Martel, B.; Ruffin, D.; Weltrowski, M.; Lekchiri, Y.; Morcellet, M. Water-soluble polymers and gels from the polycondensation between cyclodextrins and poly(carboxylic acid)s: A study of the preparation parameters. J. Appl. Polym. Sci. 2005, 97, 433–442. [Google Scholar]
  19. Morin-Crini, N.; Crini, G. Environmental applications of water-insoluble β-cyclodextrin–epichlorohydrin polymers. Prog. Polym. Sci. 2013, 38, 344–368. [Google Scholar] [CrossRef]
  20. Tonelli, A.E. Cyclodextrins as a means to nanostructure and functionalize polymers. J. Incl. Phenom. Macrocycl. Chem. 2007, 60, 197–202. [Google Scholar] [CrossRef]
  21. Munteanu, M.; Choi, S.; Ritter, H. Cyclodextrin Methacrylate via Microwave-Assisted Click Reaction. Macromolecules 2008, 41, 9619–9623. [Google Scholar] [CrossRef]
  22. Zhou, J.; Ritter, H. Cyclodextrin functionalized polymers as drug delivery systems. Polym. Chem. 2010, 1, 1552–1559. [Google Scholar] [CrossRef]
  23. Doyagüez, E.G.; Rodríguez-Hernández, J.; Corrales, G.; Fernández-Mayoralas, A.; Gallardo, A. Water-Soluble Pendant Copolymers Bearing Proline and Permethylated β-Cyclodextrin: pH-Dependent Catalytic Nanoreactors. Macromolecules 2012, 45, 7676–7683. [Google Scholar] [CrossRef]
  24. Moers, C.; Nuhn, L.; Wissel, M.; Stangenberg, R.; Mondeshki, M.; Berger-Nicoletti, E.; Thomas, A.; Schaeffel, D.; Koynov, K.; Klapper, M.; et al. Supramolecular linear-g-hyperbranched graft polymers: Topology and binding strength of hyperbranched side chains. Macromolecules 2013, 46, 9544–9553. [Google Scholar] [CrossRef]
  25. Zhao, J.; Lin, D.-Q.; Wang, Y.-C.; Yao, S.-J. A novel β-cyclodextrin polymer/tungsten carbide composite matrix for expanded bed adsorption: Preparation and characterization of physical properties. Carbohyd. Polym. 2010, 80, 1085–1090. [Google Scholar]
  26. Zhao, J.; Lin, D.-Q.; Yao, S.-J. Adsorption of rutin with a novel β-cyclodextrin polymer adsorbent: Thermodynamic and kinetic study. Carbohyd. Polym. 2012, 90, 1764–1770. [Google Scholar] [CrossRef]
  27. Tonelli, A.E. Nanostructuring and functionalizing polymers with cyclodextrins. Polymer 2008, 49, 1725–1736. [Google Scholar] [CrossRef]
  28. Alvarez-Lorenzo, C.; Concheiro, A. Molecularly imprinted materials as advanced excipients for drug delivery systems. In Biotechnology Annual Review; El-Gewely, M.R., Ed.; Elsevier: Clayton, Australia, 2006; Volume 12, pp. 225–268. [Google Scholar]
  29. Asanuma, H.; Akiyama, T.; Kajiya, K.; Hishiya, T.; Komiyama, M. Molecular imprinting of cyclodextrin in water for the recognition of nanometer-scaled guests. Anal. Chim. Acta 2001, 435, 25–33. [Google Scholar] [CrossRef]
  30. Egawa, Y.; Shimura, Y.; Nowatari, Y.; Aiba, D.; Juni, K. Preparation of molecularly imprinted cyclodextrin microspheres. Int. J. Pharm. 2005, 293, 165–170. [Google Scholar] [CrossRef]
  31. Guo, M.; Hu, X.; Fan, Z.; Liu, J.; Wang, X.; Wang, Y.; Mi, H. Imprinted polymers with cyclodextrin pseudo-polyrotaxanes as pseudo-supports for protein recognition. Talanta 2013, 105, 409–416. [Google Scholar]
  32. Kyzas, G.Z.; Lazaridis, N.K.; Bikiaris, D.N. Optimization of chitosan and β-cyclodextrin molecularly imprinted polymer synthesis for dye adsorption. Carbohyd. Polym. 2013, 91, 198–208. [Google Scholar] [CrossRef]
  33. Ng, S.M.; Narayanaswamy, R. Molecularly imprinted β-cyclodextrin polymer as potential optical receptor for the detection of organic compound. Sens. Actuator B-Chem. 2009, 139, 156–165. [Google Scholar] [CrossRef]
  34. Roche, P.J.R.; Ng, S.M.; Narayanaswamy, R.; Goddard, N.; Page, K.M. Multiple surface plasmon resonance quantification of dextromethorphan using a molecularly imprinted β-cyclodextrin polymer: A potential probe for drug–drug interactions. Sens. Actuator B-Chem. 2009, 139, 22–29. [Google Scholar] [CrossRef]
  35. Tsai, H.-A.; Syu, M.-J. Synthesis of creatinine-imprinted poly(β-cyclodextrin) for the specific binding of creatinine. Biomaterials 2005, 26, 2759–2766. [Google Scholar] [CrossRef]
  36. Liu, X.-Y.; Fang, H.-X.; Yu, L.-P. Molecularly imprinted photonic polymer based on β-cyclodextrin for amino acid sensing. Talanta 2013, 116, 283–289. [Google Scholar] [CrossRef]
  37. Binello, A.; Cravotto, G.; Nano, G.M.; Spagliardi, P. Synthesis of chitosan-cyclodextrin adducts and evaluation of their bitter-masking properties. Flavour Frag. J. 2004, 19, 394–400. [Google Scholar] [CrossRef]
  38. Binello, A.; Robaldo, B.; Barge, A.; Cavalli, R.; Cravotto, G. Synthesis of cyclodextrin-based polymers and their use as debittering agents. J. App. Polym. Sci. 2008, 107, 2549–2557. [Google Scholar] [CrossRef]
  39. Ciobanu, A.; Mallard, I.; Landy, D.; Brabie, G.; Nistor, D.; Fourmentin, S. Inclusion interactions of cyclodextrins and crosslinked cyclodextrin polymers with linalool and camphor in Lavandula angustifolia essential oil. Carbohyd. Polym. 2012, 87, 1963–1970. [Google Scholar] [CrossRef]
  40. Ciobanu, A.; Mallard, I.; Landy, D.; Brabie, G.; Nistor, D.; Fourmentin, S. Retention of aroma compounds from Mentha piperita essential oil by cyclodextrins and crosslinked cyclodextrin polymers. Food Chem. 2013, 138, 291–297. [Google Scholar] [CrossRef]
  41. Liu, H.; Cai, X.; Wang, Y.; Chen, J. Adsorption mechanism-based screening of cyclodextrin polymers for adsorption and separation of pesticides from water. Water Res. 2011, 45, 3499–3511. [Google Scholar] [CrossRef]
  42. Sikder, M.T.; Islam, M.S.; Kikuchi, T.; Suzuki, J.; Saito, T.; Kurasaki, M. Removal of Copper Ions From Water Using Epichlorohydrin Cross-Linked β-Cyclodextrin Polymer: Characterization, Isotherms and Kinetics. Water Environ. Res. 2014, 86, 296–304. [Google Scholar] [CrossRef]
  43. Kettel, M.J.; Dierkes, F.; Schaefer, K.; Moeller, M.; Pich, A. Aqueous nanogels modified with cyclodextrin. Polymer 2011, 52, 1917–1924. [Google Scholar] [CrossRef]
  44. Huang, W.Y.; Davidge, S.T.; Wu, J. Bioactive natural constituents from food sources-potential use in hypertension prevention and treatment. Crit. Rev. Food Sci. 2013, 53, 615–630. [Google Scholar]
  45. Kawano, S.; Kida, T.; Miyawaki, K.; Noguchi, Y.; Kato, E.; Nakano, T.; Akashi, M. Cyclodextrin polymers as highly effective adsorbents for removal and recovery of polychlorobiphenyl (PCB) contaminants in insulating oil. Environ. Sci. Technol. 2014, 48, 8094–8100. [Google Scholar] [CrossRef]
  46. Hernandez-Montelongo, J.; Naveas, N.; Degoutin, S.; Tabary, N.; Chai, F.; Spampinato, V.; Ceccone, G.; Rossi, F.; Torres-Costa, V.; Manso-Silvan, M.; et al. Porous silicon-cyclodextrin based polymer composites for drug delivery applications. Carbohyd. Polym. 2014, 110, 238–252. [Google Scholar] [CrossRef]
  47. Di Cagno, M.; Nielsen, T.T.; Lambertsen Larsen, K.; Kuntsche, J.; Bauer-Brandl, A. β-Cyclodextrin-dextran polymers for the solubilization of poorly soluble drugs. Int. J. Pharm. 2014, 468, 258–263. [Google Scholar]
  48. Zhang, Y.; Cai, X.; Xiong, W.; Jiang, H.; Zhao, H.; Yang, X.; Li, C.; Fu, Z.; Chen, J. Molecular insights into the pH-dependent adsorption and removal of ionizable antibiotic oxytetracycline by adsorbent cyclodextrin polymers. PLoS One 2014, 9, e86228. [Google Scholar]
  49. Wintgens, V.; Dalmas, F.; Sébille, B.; Amiel, C. Novel phosphorus-containing cyclodextrin polymers and their affinity for calcium cations and hydroxyapatite. Carbohyd. Polym. 2013, 98, 896–904. [Google Scholar] [CrossRef]
  50. Shirasawa, T.; Ueda, M.; Appell, M.; Goto, T. Use of cyclodextrin-based polymer for patulin analysis in apple juice. Mycotoxins 2013, 63, 1–8. [Google Scholar] [CrossRef]
  51. Hebeish, A.; El-Sawy, S.M.; Ragaei, M.; Hamdy, I.A.; El-Bisi, M.K.; Abdel-Mohdy, F.A. New textiles of biocidal activity by introduce insecticide in cotton-poly (GMA) copolymer containing β-Cd. Carbohyd. Polym. 2014, 99, 208–217. [Google Scholar] [CrossRef]
  52. Simões, S.M.N.; Veiga, F.; Ribeiro, A.C.F.; Figueiras, A.R.; Taboada, P.; Concheiro, A.; Alvarez-Lorenzo, C. Supramolecular gels of poly-α-cyclodextrin and PEO-based copolymers for controlled drug release. Eur. J. Pharm. Biopharm. 2014, 87, 579–588. [Google Scholar] [CrossRef]
  53. Olteanu, A.; Aramă, C.-C.; Radu, C.; Mihăescu, C.; Monciu, C.-M. Effect of β-cyclodextrins based nanosponges on the solubility of lipophilic pharmacological active substances (repaglinide). J. Incl. Phenom. Macrocycl. Chem. 2014, 1–8. [Google Scholar]
  54. Raoov, M.; Mohamad, S.; Abas, M. Synthesis and characterization of β-cyclodextrin functionalized ionic liquid polymer as a macroporous material for the removal of phenols and As(V). Int. J. Mol. Sci. 2013, 15, 100–119. [Google Scholar] [CrossRef]
  55. Gong, A.; Ping, W.; Wang, J.; Zhu, X. Cyclodextrin polymer/Fe3O4 nanocomposites as solid phase extraction material coupled with UV–vis spectrometry for the analysis of rutin. Spectrochim. Acta A 2014, 122, 331–336. [Google Scholar] [CrossRef]
  56. Ghemati, D.; Aliouche, D. Dye adsorption behavior of polyvinyl alcohol/glutaraldehyde/β-cyclodextrin polymer membranes. J. Appl. Spectrosc. 2014, 81, 257–263. [Google Scholar] [CrossRef]
  57. Bui, M.P.; Seo, S.S. Fabrication of polymerized crystalline colloidal array thin film modified β-cyclodextrin polymer for paraoxon-ethyl and parathion-ethyl detection. Anal. Sci. 2014, 30, 581–587. [Google Scholar] [CrossRef]
  58. Zhang, W.; Chen, M.; Gong, X.; Diao, G. Universal water-soluble cyclodextrin polymer–carbon nanomaterials with supramolecular recognition. Carbon 2013, 61, 154–163. [Google Scholar] [CrossRef]

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MDPI and ACS Style

Folch-Cano, C.; Yazdani-Pedram, M.; Olea-Azar, C. Inclusion and Functionalization of Polymers with Cyclodextrins: Current Applications and Future Prospects. Molecules 2014, 19, 14066-14079. https://doi.org/10.3390/molecules190914066

AMA Style

Folch-Cano C, Yazdani-Pedram M, Olea-Azar C. Inclusion and Functionalization of Polymers with Cyclodextrins: Current Applications and Future Prospects. Molecules. 2014; 19(9):14066-14079. https://doi.org/10.3390/molecules190914066

Chicago/Turabian Style

Folch-Cano, Christian, Mehrdad Yazdani-Pedram, and Claudio Olea-Azar. 2014. "Inclusion and Functionalization of Polymers with Cyclodextrins: Current Applications and Future Prospects" Molecules 19, no. 9: 14066-14079. https://doi.org/10.3390/molecules190914066

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