Supramolecular hydrogel formation based on inclusion complexation between poly(ethylene glycol)-modified chitosan and alpha-cyclodextrin

Supramolecular hydrogels have been prepared on the basis of polymer inclusion complex (PIC) formation between poly(ethylene glycol) (PEG)-modified chitosans and alpha-cyclodextrin (alpha-CD). A series of PEG-modified chitosans were synthesized by coupling reactions between chitosan and monocarboxylated PEG using water-soluble carbodiimide (EDC) as coupling agent. With simple mixing, the resultant supramolecular assembly of the polymers and alpha-CD molecules led to hydrogel formation in aqueous media. The supramolecular structure of the PIC hydrogels was confirmed by differential scanning calorimetry (DSC), X-ray diffraction, and (13)C cross-polarized/magic-angle spinning (CP/MAS) NMR characterization. The PEG side-chains on the chitosan backbones were found to form inclusion complexes (ICs) with alpha-CD molecules, resulting in the formation of channel-type crystalline micro-domains. The IC domains play an important role in holding together hydrated chitosan chains as physical junctions. The gelation property was affected by several factors including the PEG content in the polymers, the solution concentration, the mixing ratio of host and guest molecules, temperature, pH, etc. All the hydrogels in acidic conditions exhibited thermo-reversible gel-sol transitions under appropriate conditions of mixing ratio and PEG content in the mixing process. The transitions were induced by supramolecular association and dissociation. These supramolecular hydrogels were found to have phase-separated structures that consist of hydrophobic crystalline PIC domains, which were formed by the host-guest interaction between alpha-CD and PEG, and hydrated chitosan matrices below the pK(a).The formation of inclusion complexes between alpha-cyclodextrin and PEG-modified chitosan leads to the formation of hydrogels that can undergo thermo-reversible supramolecular dissociation.     

Surface properties of inclusion complexes between alpha-cyclodextrin and poly(ethylene oxide)

The surface properties of the supramolecular inclusion complex (IC) obtained from the threading of alpha-cyclodextrin (alpha-CD) onto poly(ethylene oxide) (PEO) free in solution are studied. The complexes were characterized by IR, (1)H NMR spectroscopy, and thermal analysis. The variation of the interfacial tension, gamma(int), with inclusion complex (IC) concentration and temperature were determined. The results were compared with those found for PEO under the same conditions. alpha-CD does not present surface activity. To quantify the adsorption process of IC and PEO in aqueous medium, the Gibbs equation was used. The driving force for adsorption of IC at the air/aqueous interface seems to arise from an enthalpic contribution. The wettability of the alpha-CD, PEO, and IC films with two liquids was determined by static contact angle measurements. The hydrophobicity degree was estimated. IC is more hydrophobic than PEO and alpha-CD.     

Supramolecular and biomimetic polypseudorotaxane/glycopolymer biohybrids: synthesis, glucose-surfaced nanoparticles, and recognition with lectin

A new class of supramolecular and biomimetic glycopolymer/poly(epsilon-caprolactone)-based polypseudorotaxane/glycopolymer triblock copolymers (poly(D-gluconamidoethyl methacrylate)-PPR-poly(D-gluconamidoethyl methacrylate), PGAMA-PPR-PGAMA), exhibiting controlled molecular weights and low polydispersities, was synthesized by the combination of ring-opening polymerization of epsilon-caprolactone, supramolecular inclusion reaction, and direct atom transfer radical polymerization (ATRP) of unprotected D-gluconamidoethyl methacrylate (GAMA) glycomonomer. The PPR macroinitiator for ATRP was prepared by the inclusion complexation of biodegradable poly(epsilon-caprolactone) (PCL) with alpha-cyclodextrin (alpha-CD), in which the crystalline PCL segments were included into the hydrophobic alpha-CD cavities and their crystallization was completely suppressed. Moreover, the self-assembled aggregates from these triblock copolymers have a hydrophilic glycopolymer shell and an oligosaccharide threaded polypseudorotaxane core, which changed from spherical micelles to vesicles with the decreasing weight fraction of glycopolymer segments. Furthermore, it was demonstrated that these triblock copolymers had specific biomolecular recognition with concanavalin A (Con A) in comparison with bovine serum albumin (BSA). To the best of our knowledge, this is the first report that describes the synthesis of supramolecular and biomimetic polypseudorotaxane/glycopolymer biohybrids and the fabrication of glucose-shelled and oligosaccharide-threaded polypseudorotaxane-cored aggregates. This hopefully provides a platform for targeted drug delivery and for studying the biomolecular recognition between sugar and lectin.     

两亲三元壳寡糖衍生物的合成及其包合物的研究

本文报道了新型水溶性甲氧基聚乙二醇-b-聚己内酯两亲嵌段共聚物接枝壳寡糖(COS-g-PCL-b-MPEG)共聚物的合成, 研究了两亲三元COS衍生物的合成及在水溶液中α-CD与其的包合作用.     

Supramolecular hydrogels induced rapidly by inclusion complexation of poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) block copolymers with alpha-cyclodextrin in aqueous solutions

On the basis of the synthesis of water-soluble poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) block copolymers, the supramolecular hydrogels were fabricated rapidly in aqueous solutions by their inclusion complexation with alpha-cyclodextrin. X-ray diffraction (XRD) analyses confirmed the supramolecular self-assemblies of alpha-cyclodextrin threaded onto amphiphilic PCL-PEG-PCL block copolymers. The resulting hydrogels display a high degree of elasticity, with the storage modulus (G') greater than the loss modulus (G') over the entire range of frequency. Moreover, their viscosity greatly diminished as they were sheared. By controlling the molecular weight of the PEG component in the block copolymers and the content of the block copolymer, their rheological properties could be modulated. Such hydrogel materials have the potential to be used as tissue engineered scaffolds, biosensors in the human body, and carriers for controlled drug delivery.     

Self-assembly in magnetic supramolecular hydrogels

Most recent advances in the synthesis of supramolecular hydrogels based on low molecular weight gelators (LMWGs) have focused on the development of novel hybrid hydrogels, combining LMWGs and different additives. The dynamic nature of the noncovalent interactions of supramolecular hydrogels, together with the specific properties of the additives included in the formulation, allow these novel hybrid hydrogels to present interesting features, such as stimuli-responsiveness, gel-sol reversibility, self-healing and thixotropy, which make them very appealing for multiple biomedical and biotechnological applications. In particular, the inclusion of magnetic nanoparticles in the hydrogel matrix results in magnetic hydrogels, a particular type of stimuli-responsive materials that respond to applied magnetic fields. This review focuses on the recent advances in the development of magnetic supramolecular hydrogels, with special emphasis in the role of the magnetic nanoparticles in the self-assembly process, as well as in the exciting applications of these materials.     

Study on the supramolecular systems of 5-(2-hydroxy phenyl)-10,15,20-tris (4-methoxy phenyl) porphyrin with cyclodextrins

In neutral phosphate buffer solutions of pH 7.4, the inclusive complexation of 5-(2-hydroxy phenyl)-10,15,20-tris(4-methoxy phenyl) porphyrin (o-HTPP) with alpha-cyclodextrin (alpha-CD), beta-CD, heptakis (2,3,6-tri-O-methyl)-beta-CD (TM-beta-CD), SBE-beta-CD, HP-beta-CD and gamma-CD has been examined by means of UV-vis and fluorescence spectroscopy. The formation of inclusion complexes has been confirmed on the base of changes of spectroscopy properties. The o-HTPP forms 1:2 inclusion complexes with TM-beta-CD and 1:1 inclusion complexes with the other five cyclodextrins. The formation constants (K) of o-HTPP for the formation of the inclusion complexes have been estimated from the absorbance and fluorescence intensity changes in neutral phosphate buffer solutions. The K value (2.89x10(7)), which is the formation constant for the formation of the 1:2 inclusion supramolecular, is nearly 10(4) times than those of the 1:1 inclusion complexes. Compared to the other five cyclodextrins, the strongest inclusion ability of TM-beta-CD can be explained that the hydrogen bond plays significant role in the inclusion process. UV-vis experiments also showed that the cavity of TM-beta-CD causes the transform of the state of o-HTPP. In addition (1)H NMR data and 2D-ROSEY NMR spectra support the inclusion conformation of the o-HTPP-CD supramolecular system, indicating the interaction mechanism of inclusion processes.     

Demicellization of a mixture of cationic-anionic hydrogenated/fluorinated surfactants through selective inclusion by alpha- and beta-cyclodextrin

The interactions between alpha- and beta-cyclodextrin (alpha-/beta-CD) and an equimolar mixture of octyltriethylammonium bromide (OTEAB) and sodium perfluorooctanoate (SPFO) were studied by 1H and 19F NMR, surface tension, conductivity, and dynamic light scattering. It was shown that beta-CD could destroy the mixed micelles of OTEAB-SPFO by selective inclusion of SPFO. As beta-CD was added, the system was observed to undergo a process like this: beta-CD preferentially included SPFO to form 1:1 beta-CD/SPFO complexes. As the inclusion of SPFO was almost saturated, the mixed micelles broke and all OTEAB was released and exposed to aqueous surroundings. Then 1:1 beta-CD/OTEAB and 2:1 beta-CD/SPFO complexes significantly formed simultaneously. Contrary to beta-CD, alpha-CD exhibited selective inclusion to OTEAB and only weak association with SPFO. alpha-CD could also destroy the mixed micelles of OTEAB-SPFO; however, the demicellization ability of alpha-CD is much smaller than that of beta-CD. These conclusions were also well supported by the calculations of binding constants and DeltaG degrees . Different from the complexes of CD/conventional surfactants, the complexes of beta-CD/SPFO or alpha-CD/OTEAB formed by selective inclusion of CD in the mixed cationic-anionic surfactants may have contributed to the surface activity of the aqueous mixtures. The complexes of alpha-CD/OTEAB showed much more significant contribution to the surface activity than that of the complexes of beta-CD/SPFO.     

Supramolecular hydrogels formed by pyrene-terminated poly(ethylene glycol) star polymers through inclusion complexation of pyrene dimers with γ-cyclodextrin

Novel supramolecular hydrogels were formed between pyrene-terminated poly(ethylene glycol) star polymers and γ-cyclodextrin (γ-CD), through the inclusion complexation of dimers of the pyrene terminals with γ-CD, where γ-CD was directly used as a supramolecular cross-linking reagent without any modification.     

Supramolecular Polymer Hydrogels from Bolaamphiphilic L‐Histidine and Benzene Dicarboxylic Acids: Thixotropy and Significant Enhancement of EuIII Fluorescence

Supramolecular polymers from the bolaamphiphilic L ‐histidine ( BolaHis ) and benzene dicarboxylic acids (o‐phthalic acid, OPA ; isophthalic acid, IPA and terephthalic acid, TPA ) were found to form hydrogels although neither of the single components could gel water. It was suggested that the hydrogen bond and ionic interactions among different imidazole and carboxylic acid groups are responsible for the formation of the supramolecular polymer as well as the hydrogel formation. Depending on the structures of the dicarboxylic acids, different behaviors of the gels were observed. The hydrogels from OPA / BolaHis and IPA / BolaHis showed thixotropic properties, that is, the hydrogel was destroyed by hand shaking and then slowly gelated again at room temperature. However, the hydrogels of TPA / BolaHis could not. Interestingly, when Eu^III was doped into IPA / BolaHis supramolecular polymers, very strong luminescence enhancement was observed. FT‐IR spectroscopies and XRD analysis revealed that the strong luminescence enhancement could be attributed to the matched supramolecular nanostructures, which render the correct binding and a good dispersion of Eu^III ions. The work offers a new approach for fabricating functional hydrogels through the supramolecular polymers.     

Injectable supramolecular hybrid hydrogels formed by MWNT‐grafted‐poly(ethylene glycol) and α‐cyclodextrin

Poly(ethylene glycol)‐grafted‐multiwalled carbon nanotube (MWNT‐g‐PEG) was synthesized by a coupling reaction and formed inclusion complexes (ICs) after selective threading of the PEG segment of the MWNT‐g‐PEG through the cavities of α‐cyclodextrins (α‐CDs) units. The polypseudorotaxane structures of the as‐obtained hydrogels were confirmed by ¹H NMR, X‐ray diffraction and DSC analyses. The complexation of the PEG segments with α‐CDs and the hydrophobic interaction between the MWNT resulted in the formation of supramolecular hybrid hydrogels with a strong network. Thermal analysis showed that the thermal stability of the hydrogel was substantially improved by up to 100 °C higher than that of native hydrogel. The resultant hybrid hydrogels were found to be thixotropic and reversible, and could be applied as a promising injectable drug delivery system. The mechanical strength of the hybrid hydrogels was greatly improved in comparison with that of the corresponding native hydrogels. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3145–3151, 2010     

Preparation of PEO-b-PPO-b-PEO/α-cyclodextrin supramolecular hydrogels hybridized with exfoliated graphite nanoplates

Abstract

In this work, an effective method was developed to prepare novel PEO-b-PPO-b-PEO (EPE)/α-cyclodextrin (α-CD) supramolecular hydrogels containing exfoliated graphite nanoplates (xGNPs) by mixing an aqueous solution of α-CD with an aqueous dispersion of xGNPs at the presence of amphiphilic EPE copolymer. The EPE copolymer played three important roles in the preparation process: (1) as an exfoliating agent to break expanded graphites into xGNPs under ultrasonication, (2) as a dispersant to stabilize xGNPs in the aqueous solution, and （3）as a component to form the inclusion complexes with α-CD. The resultant xGNPs/EPE/α-CD hybridized hydrogels were characterized by scanning electron microscopy, wide-angle X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy, which confirmed not only the formation of supramolecular hydrogel structure but also the homogenous dispersion of xGNPs in the hydrogel matrix. It was found that the existence of xGNPs can accelerate the speed of gel formation in comparison with that of the native EPE/α-CD hydrogel. Additionally, the water-retention ability and the release behavior of vancomycin hydrochloride for the xGNPs/EPE/α-CD hybridized hydrogels were investigated.     

Preparation and characterization of polypseudorotaxanes based on block-selected inclusion complexation between poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) triblock copolymers and alpha-cyclodextrin

A series of new polypseudorotaxanes were synthesized in high yields when the middle poly(ethylene oxide) (PEO) block of poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) (PPO-PEO-PPO) triblock copolymers was selectively recognized and included by alpha-cyclodextrin (alpha-CD) to form crystalline inclusion complexes (ICs), although the middle PEO block was flanked by two thicker PPO blocks, and a PPO chain had been previously thought to be impenetrable to alpha-CD. X-ray diffraction studies demonstrated that the IC domains of the polypseudorotaxanes assumed a channel-type structure similar to the necklace-like ICs formed by alpha-CD and PEO homopolymers. Solid-state CP/MAS (13)C NMR studies showed that the alpha-CD molecules in the polypseudorotaxanes adopted a symmetrical conformation due to the formation of ICs. The compositions and stoichiometry of the polypseudorotaxanes were studied using (1)H NMR, and a 2:1 (ethylene oxide unit to alpha-CD) stoichiometry was found for all polypseudorotaxanes although the PPO-PEO-PPO triblock copolymers had different compositions and block lengths, suggesting that only the PEO block was closely included by alpha-CD molecules, whereas the PPO blocks were uncovered. The hypothesis was further supported by the differential scanning calorimetry (DSC) studies of the polypseudorotaxanes. The glass transitions of the PPO blocks in the polypseudorotaxanes were clearly observed because they were uncovered by alpha-CD and remained amorphous, whereas the glass-transition temperatures increased, because the molecular motion of the PPO blocks was restricted by the hard crystalline phases of the IC domains formed by alpha-CD and the PEO blocks. The thermogravimetric analysis (TGA) revealed that the polypseudorotaxanes had better thermal stability than their free components due to the inclusion complexation. Finally, the kinetics of the threading process of alpha-CD onto the copolymers was also studied. The findings reported in this article suggested interesting possibilities in designing other cyclodextrin ICs and polypseudorotaxanes with block structures.     

Guest-free self-assembly of alpha-cyclodextrins leading to channel-type nanofibrils as mesoporous framework

Guest-free alpha-cyclodextrin self-assembly (alpha-CD-SA) was successfully obtained through a simple treatment such as sonication of alpha-CD in a specific solvent. From wide-angle X-ray diffraction (WAXD), it was found that the crystalline structure of alpha-CD changed upon increasing the treatment time, resulting in alpha-CD-SA in which the alpha-CDs were closely packed in the vertical direction and hexagonally aligned in the horizontal direction (what is called as "channel structure"). In particular, these structures were developed only in tetrahydrofuran (THF) as a specific solvent. In addition, it was found by inclusion experiment and field-emission scanning electron microscopy (FE-SEM) that propionic acid was able to be included into the channel of alpha-CD-SA and that alpha-CD-SA had alpha-CD bundles with a fibril-like shape, respectively. These results demonstrate that the alpha-CD-SA consists of nanofibril-like alpha-CD bundles with cylindrical nanopores open at least at one end, resulting from the dispersion of alpha-CD molecules by sonication in THF and the subsequent re-formation of strong hydrogen bonding between the alpha-CDs with the aid of THF (so-called "slow recrystallization"). Interestingly, it was observed from FE-SEM and nitrogen adsorption-desorption measurement that the alpha-CD-SA had a wormhole-like mesopore with inkbottle shape (average desorption pore size = ca. 25 nm). This mesoporous structure was considered to be attributed to the formation of a mesoporous framework by the disordered aggregation of the nanofibril-like alpha-CD bundles.     

Dynamic Hydrogels from Host–Guest Supramolecular Interactions

Hydrogel biomaterials are pervasive in biomedical use. Applications of these soft materials range from contact lenses to drug depots to scaffolds for transplanted cells. A subset of hydrogels is prepared from physical cross‐linking mediated by host–guest interactions. Host macrocycles, the most recognizable supramolecular motif, facilitate complex formation with an array of guests by inclusion in their portal. Commonly, an appended macrocycle forms a complex with appended guests on another polymer chain. The formation of poly(pseudo)rotaxanes is also demonstrated, wherein macrocycles are threaded by a polymer chain to give rise to physical cross‐linking by secondary non‐covalent interactions or polymer jamming. Host–guest supramolecular hydrogels lend themselves to a variety of applications resulting from their dynamic properties that arise from non‐covalent supramolecular interactions, as well as engineered responsiveness to external stimuli. These are thus an exciting new class of materials.     

Synthesis and characterization of maltose-based amphiphiles as supramolecular hydrogelators

Low molecular mass amphiphilic glycolipids have been prepared by linking a maltose polar head and a hydrophobic linear chain either by amidation or copper(I)-catalyzed azide-alkyne [3 + 2] cycloaddition. The liquid crystalline properties of these amphiphilic materials have been characterized. The influence of the chemical structure of these glycolipids on the gelation properties in water has also been studied. Glycolipids obtained by the click coupling of the two components give rise to stable hydrogels at room temperature. The fibrillar structure of supramolecular hydrogels obtained by the self-assembly of these gelators have been characterized by electron microscopy. Fibers showed some torsion, which could be related with a chiral supramolecular arrangement of amphiphiles, as confirmed by circular dichroism (CD). The sol-gel transition temperature was also determined by differential scanning calorimetry (DSC) and NMR.     

基于环糊精包结络合作用的大分子自组装

本文综述了基于环糊精包结络合作用的大分子自组装的研究进展,包括：（1) 线型、梳型、多臂星型或超支化聚合物与环糊精或其二聚体自组装形成多聚轮烷（分子项链）、多聚准轮烷、双多聚（准）轮烷、分子管、双分子管、超分子凝胶及其应用;（2）桥联环糊精与桥联客体分子自组装制备线型或超支化超分子聚合物;（3）温度、pH值、光及客体分子刺激响应智能体系; （4) 通过亲水性的环糊精线型均聚物与含金刚烷的疏水性聚合物之间的包结络合作用来制备高分子胶束及其空心球等。     

Effect of guest hydrophobicity on water sorption behavior of oligomer/alpha-cyclodextrin inclusion complexes

Cyclomaltohexaose (alpha-cyclodextrin, alpha-CD) can form inclusion complexes (ICs) with polymer molecules in the columnar crystal structure in which alpha-CD molecules stack to form a molecular tube. Complementary water vapor sorption and wide-angle X-ray diffractomery (WAXD) were performed on oligomer/alpha-CD ICs to determine their structures and stabilities. To discern the effect of guest molecule hydrophobicity on water adsorption isotherms, polyethylene glycol (PEG, MW = 600 g/mol) and hexatriacontane (HTC) guests were used. Sorption isotherms for PEG/alpha-CD IC are similar to those obtained for pure alpha-CD and PEG, suggesting the presence of dethreaded PEG in the sample. WAXD collected before and after water vapor sorption of PEG/alpha-CD IC indicated a partial conversion from columnar to cage crystal structure, the thermodynamically preferred structure for pure alpha-CD, due to dethreading of PEG. This behavior does not occur for HTC/alpha-CD IC. Sorption isotherms collected at 20, 30, 40, and 50 degrees C allowed the calculation of the isosteric heats of adsorption and the integral entropies of adsorbed water which are characterized by minima that indicate the monolayer concentration of water in the ICs.     

Tunable supramolecular hydrogel for in situ encapsulation and sustained release of bioactive lysozyme

To develop new matrices for the entrapment and sustained release of bioactive lysozyme, a series of supramolecular hydrogels based on α-cyclodextrin (α-CD) and water-soluble poly(ε-caprolactone)-poly(ethylene glycol) block copolymer (PCL-b-PEG) were prepared in the presence of chicken egg lysozyme. Different from commonly used polymeric microspheres and chemically crosslinked hydrogels for lysozyme encapsulation, such hydrogel matrices could be formed under mild conditions without high temperature and the use of chemical emulsifiers or crosslinkers. Their gelation rate, mechanical strength and shear viscosity as well as the release behavior for the encapsulated lysozyme could be tuned easily by the change of α-CD or PCL-b-PEG amount. For the encapsulated lysozyme, its conformation and biological activity could be well maintained when compared to native lysozyme. For the resultant supramolecular hydrogels, they were also confirmed to have a good biocompatibility by MTT assay using mice skin fibroblast (L929).     

Release of bioactive volatiles from supramolecular hydrogels: influence of reversible acylhydrazone formation on gel stability and volatile compound evaporation

In the presence of alkali metal cations, guanosine-5'-hydrazide (1) forms stable supramolecular hydrogels by selective self-assembly into a G-quartet structure. Besides being physically trapped inside the gel structure, biologically active aldehydes or ketones can also reversibly react with the free hydrazide functions at the periphery of the G-quartet to form acylhydrazones. This particularity makes the hydrogels interesting as delivery systems for the slow release of bioactive carbonyl derivatives. Hydrogels formed from 1 were found to be significantly more stable than those obtained from guanosine. Both physical inclusion of bioactive volatiles and reversible hydrazone formation could be demonstrated by indirect methods. Gel stabilities were measured by oscillating disk rheology measurements, which showed that thermodynamic equilibration of the gel is slow and requires several cooling and heating cycles. Furthermore, combining the rheology data with dynamic headspace analysis of fragrance evaporation suggested that reversible hydrazone formation of some carbonyl compounds influences the release of volatiles, whereas the absolute stability of the gel seemed to have no influence on the evaporation rates.