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Rupture of Pluronic Micelles by Di-Methylated β-Cyclodextrin Is Not Due to Polypseudorotaxane Formation
Abstract
Spectroscopic measurements (uv/vis absorbance and fluorescence) and time-resolved small-angle neutron scattering experiments (TR-SANS) were used to follow the breakdown of Pluronic micelles by heptakis(2,6-di-O-methyl)-β-cyclodextrin (DIMEB) over time in order to elucidate the mechanism of micellar rupture, generally attributed to polypseudotorotaxane (PR) formation between the cyclodextrin and the central hydrophobic PPO block. The spectroscopic measurements with two different probes (methyl orange and nile red) suggest that very rapid changes (on the order of seconds) take place when mixing DIMEB with F127 Pluronic and that no displacement of the probe from the cyclodextrin cavity occurs, which is in disagreement with PR formation. TR-SANS measurements demonstrate for the first time that the micelles are broken down in less than 100 ms, which categorically rules out PR formation as the mechanism of rupture. In addition, the same mechanism is demonstrated with other Pluronics, P85 and P123. In the latter case, after micellar rupture, lamellar structures are seen to form over a longer period of time, thus suggesting that after the instantaneous micellar disruption, further, longer-scale rearrangements are not excluded.
... To assess the probable binding site of the probe within the microheterogeneous media, the sensitivity of the emission profile of NHM towards the polarity of the medium has been exploited by analyzing the emission profiles of the probe, incorporated within the polymeric units as compared to the emission profiles obtained by dissolving the probe in water-dioxane mixtures of altering compositions having precisely known polarity in terms of the standard E T (30) scale [23]. The standard E T (30) transfer transition band maxima of the betaine dye, 2,6-diphenyl-4 (2,4,6-triphenyl-1-pyridino)phenolate in the said dioxane-water mixtures. ...
... To assess the probable binding site of the probe within the microheterogeneous media, the sensitivity of the emission profile of NHM towards the polarity of the medium has been exploited by analyzing the emission profiles of the probe, incorporated within the polymeric units as compared to the emission profiles obtained by dissolving the probe in water-dioxane mixtures of altering compositions having precisely known polarity in terms of the standard E T (30) scale [23]. The standard E T (30) transfer transition band maxima of the betaine dye, 2,6-diphenyl-4 (2,4,6-triphenyl-1-pyridino)phenolate in the said dioxane-water mixtures. Although the polarity of a microheterogeneous environment cannot be directly compared to that of a homogeneous fluid owing to the possibility of specific solvation of the probe as well as the gross approximation that these binary solvents mimic the real biomimicking environment; a qualitative estimate of the micropolarity around the fluorophore generally yields consistent results. ...
... After a thorough individual understanding of the interactions of the probe NHM with the triblock copolymer micelle and β-CD, our effort was to explore the probable location of NHM following the interaction of P123 micelles with β-CD by virtue of the modulations of the spectroscopic properties of the probe. Literature reports suggest that at lower concentrations of cyclodextrin, the macrocyclic cavity starts threading onto the PEO block and gradually localizes preferentially on the hydrophobic middle group (PPO) of the Pluronic unit, thereby reducing the thermodynamic convenience for micellization [29,30]. This situation is proliferated further with increasing concentration of the macrocycle, eventually leading to the rupture of the micelles followed by a phase separation owing to the formation of insoluble CD-P123 pseudorotaxanes [29][30][31][32]. ...
The present study delves into the interaction of a potent cancer-cell photosensitizer Norharmane (NHM) with non-ionic triblock copolymer P123, followed by the assessment of the stability of the formed complex in the presence of β-cyclodextrin (β-CD). Spectroscopic results unveil the modulation of the prototropic equilibrium of NHM within the constrained microheterogeneous medium of the copolymer micelle to be favoured towards the neutral species of NHM over the cationic counterpart; which has been aptly rationalized invoking the key role of hydrophobic interaction in the association process and is further reinforced from steady-state and time-resolved spectroscopic measurements. The micropolarity of the probe–binding site has been evaluated by the archetypal ET(30) analysis revealing that the cationic probe remains in the corona region of the micelle instead of penetrating deeper into the micellar core region. Moreover, the effect of β-CD on the stability of the NHM–bound P123 aggregates has also been investigated, revealing that β-CD can be used as a potential host for the release of the micelle–encapsulated drug through an inclusion complex formation with the P123 monomers. The result is expected to be of potential interest from medical perspective owing to the context of efficient drug release at their potential sites.
... 12,13 Dimethylated β-cyclodextrin (DIMEB), which has two hydrogens substituted by a methyl group on each glucose unit, interacts with Pluronic micelles by hindering micellization, breaking them up completely at high DIMEB/ Pluronic ratio. 1,2,7 This destructive interaction is surprisingly selective and is not observed (or much reduced) with other CD derivatives. 7 The demicellisation induced by DIMEB, probably linked to an optimum balance between hydrophobicity and hydrogen-bonding ability, seems to be quite a generic feature of this cyclodextrin, as recently shown for X-shaped PEO-PPO block copolymers (poloxamines or Tetronics). ...
... 1 Interestingly, the extent of this effect is not only controlled by composition (DIMEB/F127 ratio) but also strongly dependent on the nature of the loaded drug: some drugs hinder DIMEB disruptive effect (thus "protecting" the micelles), but to varying extents; the mechanisms, however, are not understood. 2,16 The current study focuses on physiological temperature (37°C ). Not only is this temperature more relevant to drug studies, but by increasing the temperature several changes occur: micellization is enhanced, drug partitioning increases, 17,18 while drug-CD binding generally decreases. ...
... Aqueous stock solutions of (1) drug alone, (2) drug/F127, and (3) drug/DIMEB, as well as combined (4) drug/ F127/DIMEB were prepared by weight. For partition coefficient determination, solutions of different F127 concentrations were prepared by mixing the appropriate amount of solutions (1) and (2). For the determination of drug/CD binding constants in the absence and the presence of F127, solutions (3) and (1) were mixed with (4) and (2), respectively. ...
Polymeric micelles, in particular PEO-PPO-based Pluronic, have emerged as promising drug carriers, while cyclodextrins, cyclic oligosaccharides with an apolar cavity, have long been used for their capacity to form inclusion complexes with drugs. Dimethylated β-cyclodextrin (CD) has the capacity to fully break-up F127 Pluronic micelles, while this effect is substantially hindered if drugs are loaded within the micellar aggregates. Four drugs were studied at physiological temperature: lidocaine (LD), pentobarbital sodium salt (PB), sodium naproxen (NP), and sodium salicylate (SAL); higher temperatures shift the equilibrium towards higher drug partitioning and lower drug:CD binding compared to 25°C.1 The impact of drugs on micellar structure was characterised by small-angle neutron scattering (SANS), while their solubilisation locus was revealed by 2D NOESY NMR. UV and fluorescence spectroscopy, Dynamic and Static Light Scattering were employed to measure a range of micellar properties and drug:CD interactions: binding constant, drug partitioning within the micelles, critical micellar concentration of the loaded micelles, aggregation number (Nagg). Critically, time-resolved SANS (TR-SANS) reveal that micellar break-up in the presence of drugs is substantially slower (100s of seconds) than for the free micelles (< 100 ms).2 These results combined together give new insights into the mechanisms of protection of the drugs against CD-induced micellar break-up. The outcomes are practical guidelines to improve the design of drug delivery systems as well as an improved understanding of competitive assembly mechanisms leading to shape and function modulation.
... On the other hand, the interactions between modified b-CDs and block copolymers have been less investigated in the literature. In the case of mixtures of heptakis (2,6-di-omethyl)-b-CD and Pluronics, such as the F127 (PEO 107-PPO 70 PEO 107 ), P85 (PEO 39 PPO 52 PEO 39 ) and P123 (PEO 20 PPO 70 PEO 20 ), it has been shown that the micellar rupture occurs with extremely fast kinetics, excluding the possibility of polypseudorotaxane formation via inclusion complexes [25]. Interestingly, in the case of Pluronic P123, the authors have reported a possible restructuration of the micelles toward swollen lamella, with an interlayer spacing much higher than the typical values reported in literature with conventional swelling agents [26]. ...
... Moreover, the nature of the interactions involved in the self-assembly process appeared to be highly sensitive to the substitution degree, nature and position of the substituents in modified cyclodextrins. Thus, in contrast to the micellar rupture observed with the heptakis (2,6-di-o-methyl)-b-CD, Dreiss and coworkers [25] reported that, under similar experimental conditions, the micelles remain intact in the presence of other substituted b-cyclodextrin derivatives, such as the 2,3,6-trimethyl-b-CD, 2-hydroxyethyl-b-CD and 2-hydroxypropyl-b-CD. ...
... Nanoparticles were synthesized by a sol-gel method reported by Yoldas [29]. In a dry 250 mL flask, 185 mL of hot distilled water (85°C) was added fast to 25 4-4.8). Under these conditions, the concentration of aluminum in the sol was determined by weight loss on ignition at 1,000°C and was estimated to be 0.5 mol/L. ...
Supramolecular assemblies formed between cyclodextrins and block copolymers can be efficiently used as templates for the preparation of mesoporous materials with controlled porosity. In this work, we use dynamic light scattering (DLS) and viscosity measurements to follow the variations occurring in the size and morphology of the triblock copolymer poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (P123) micelles in the presence of various amounts of randomly methylated β-cyclodextrin (RAMEB). The results obtained with a series of solution compositions reveal that the cyclodextrin-to-copolymer (RAMEB/P123) molar ratio plays a crucial role in the growth rate of the micelles. At low RAMEB/P123 molar ratios (below ~7.5), a swelling effect of the cyclodextrin in the P123 micelles is noticed together with a modification of the micellar curvature from spherical to ellipsoidal. At high molar ratios (~7.5 and above), an abrupt transition toward large supramolecular assemblies, which no longer resemble micelles, occurs. When the RAMEB-swollen P123 micelles are used as templates to direct the self-assembly of colloidal boehmite nanoparticles, mesoporous γ-Al2O3 materials with high surface areas (360–400 m2/g), tunable pore sizes (10–20 nm), large pore volumes (1.3–2.0 cm3/g) and fiberlike morphologies are obtained under mild conditions. The composition of the mixed micellar solution, in particular the cyclodextrin-to-copolymer molar ratio, appears to be a key factor in controlling the porosity of alumina.
... Cyclodextrins (CDs) are a group of cyclic oligosaccharides and they possess molecular structures with a configuration of a truncated cone [1], consisting of a hydrophobic interior environment and hydrophilic exterior surfaces. This configuration permits them to accommodate diverse molecules into their cavities. ...
... CDs, also called cycloamyloses, cyclomaltoses, or Schardinger dextrins [8], due to their backbone consisting of sugars, are a group of cyclic oligosaccharides composed of six (α-CD), seven (β-CD), or eight (γ-CD) D(+)-glucopyranose units, linked by α-1,4 glycosidic [9], shaping supramolecular structures with a toroidal configuration [1]. Due to the formation of sugars, the secondary 2-and 3-hydroxy groups are extended from the broader edge, whereas the primary 6-hydroxy groups are located at the narrower edge [10]. ...
Cyclodextrin (CD)-block copolymer hybrid systems have recently received great attention from the pharmaceutical and materials research community because this combination can result in new biomaterials and supramolecular structures, which possess the physicochemical and thermotropic properties of both classes of materials. Different structures of CD-block copolymer systems have been described (i.e., micelles, vehicles, core-shell structures, nanospheres, and membranes) and they can encapsulate active pharmaceutical ingredients or other bioactive compounds. The aim of this review is to summarize several examples, the properties, the morphological and physicochemical characteristics, the added value, the techniques used for their preparation and characterization, as well as the limitations of CD-block copolymer systems. Taking into consideration the wide variety of block copolymers and CD materials and the expected beneficial characteristics/behavior following their complexation, we could suggest them as new-generation formulations in the upcoming years.
... The effects of various CDs on the micellization and gelation of pluronics have also been reported. For such systems, changes in micellar concentration, in gelation, as well as changes of the hydration layer around the polymer chains during phase transition, when CDs are placed among polymeric chains, can be the result of pseudorotaxane formation [29][30][31][32][33]. Being water soluble, CDs will be more probable to target the region of the micelles placed at the water interface. ...
Cyclodextrins are natural cyclic oligosaccharides with a cone shape delimiting a hydrophobic cavity. The rims of cyclodextrins can be functionalized in order to improve their properties. Based on this, cyclodextrins can be linked to polymer chains, which further allows the tuning of the polymer properties. This review describes the methods of polymer functionalization with cyclodextrins and highlights the changes in the physicochemical properties of these materials. This chapter is focused on polymers in solution and in gel states. Cyclodextrin-based polymers are evaluated by various physicochemical methods, such as rheology, calorimetry, and spectroscopy (electron paramagnetic resonance, fluorescence, nuclear magnetic resonance (NMR), Fourier transform infrared (FT-IR), etc.). Both natural and synthetic polymers are considered in this chapter.
... In this scenario, a competition is established between the threading of the macrocycle along the arms of the poloxamine and its selfaggregation. 37,48,53 We have considered the reaction of 1% T904 at 40°C, conditions in which the surfactant is aggregated and the scattering dominated by the micelles, 48 with 2.5% α-CD, which is below the threshold of formation of the insoluble PPR network (Figure 3), to avoid the scattering from large aggregates. Figure 8A shows the evolution of the scattering over time, in which the diminution of the intensity unambiguously shows the breakup of the micelles by the action of the CD. ...
Pseudo-polyrotaxanes (PPRs) are supramolecular host-guest complexes constituted by the reversible threading of a macrocycle along a polymer chain. The resuting dynamic "molecular necklaces" offer potential applications in nanotechnology, drug delivery, and biomaterials. We report the formation of PPRs by threading of cyclodextrins (CDs), cyclic oligosaccharides, onto X-shaped PEO-PPO block copolymers with two opposite presentation of their hydrophobic and hydrophilic blocks: Tetronic 904 (T904) and its reverse counterpart Tetronic 90R4 (T90R4). We assess the effects that relative block position on the polymeric surfactants and cavity size of CD have on the composition, morphology, thermodynamics, and kinetics of PPRs by using a combination of X-ray diffraction, scanning electron microscopy, NMR, UV-vis spectroscopy, and time-resolved small-angle neutron scattering (TR-SANS). Solid PPRs with lamellar microstructure and crystalline channel-like structures are obtained with native CDs and both Tetronics above a threshold concentration of the macrocycle, which varies with the type of CD and surfactant. While γ-CD can form PPRs with both Tetronics, α-CD only forms a PPR with T90R4 at high concentrations. The results can be explained in terms of the preferential complexation of α-CD with EO and γ-CD with PO monomers, which also has a direct impact on the kinetics of PPR formation. Thermodynamic parameters of the reaction were obtained from the analysis of the stoichiometries and threading times as a function of temperature by using a model based on the Eyring equation. Negative enthalpies and positive entropies are obtained in all cases, and reactions are thermodynamically most favorable in the case of α-CD with T904 and γ-CD with T90R4. TR-SANS experiments reveal an increase in the radius of gyration of the unimers over time, consistent with CD threading and further expansion of the PPR. Above the CMT, α-CD threads the unimers to form the PPR, with no effect on the structure of T904 micelles, whose volume fraction decreases due to the shift of micellization equilibrium.
... The chemical structures of the investigated compounds are shown in Fig. 2. Nile red (NR) was chosen as a model drug (interacting with the CD cavity) because of its hydrophobic fluorophore and its stable fluorescence. NR has been previously studied as a polarity-sensitive fluorescence probe suitable for monitoring of structural transformations and intermolecular interactions upon micropolarity changes in the surroundings [13,14]. ...
The purpose of this work is to investigate the inclusion complexation between a novel amphiphilic biotransesterified cyclodextrin (CD), incorporated in nanostructured environment, and a model drug compound. A water-insoluble γ-cyclodextrin derivative (γ-CD-C10), polysubstituted with multiple (n=7-8) decanoyl chains (C10) on the secondary face, is produced by enzymatically-assisted esterification. The γ-CD-C 10 derivative is embedded in amphiphilic nanoenvironment created by self-assembly with the lipophilic dye Nile red (NR) and the non-ionic surfactant polysorbate 80 (P80). The inclusion complexation and the environmental effects upon the γ-CD-C10/NR/P80 nanoparticle (NP) formation, in a multilevel self-assembly approach, are investigated by means of steady-state fluorescence and Förster resonance energy transfer (FRET) techniques. Quasi-elastic light scattering (QELS) is used to control the NP size distribution during the sequential steps of the assembling process.
In this study, we designed and developed systems composed of poly(ethylene-oxide)-b-poly(ε-caprolactone) block copolymers, of different molecular weights and compositions, non-ionic surfactant and cyclodextrins. The innovation of this study lays in...
In this work, the inclusion complexes of alkyl ethoxy carboxylates with α-cyclodextrin (αCD) and β-cyclodextrin (βCD) were investigated. The thermodynamics of the complexation process was probed by isothermal titration calorimetry (ITC) and volumetry as a function of the degree of ionization of the surfactant. The complexation process was shown to be an enthalpically driven pH-independent process. For both types of cyclodextrins, the complexes were found to spontaneously self-assemble into highly-ordered supramolecular aggregates probed by small-angle neutron scattering and electron and optical microscopy. Herein, we report the formation of thin platelets for nonionized surfactant systems and equally spaced multilayered hollow cylinders for ionized systems in a hierarchical self-assembly process. In addition, the analysis allowed unveiling the effect of the number of ethylene oxides in the surfactants and the CD cavity size on the morphology of the aggregates. Finally, this study also highlights the importance of examining the tuning parameters' influence on the short and long-range interactions involved in the control of the assembly process.
The present work examines the behavior of salicylic acid (SAL)-loaded F127 micelles as drug nanocarriers for controlled release by means of interaction with 2,6-dimethyl-β-cyclodextrin (DIMEB) in the intestine at basic pH = 7–8, both important excipients, of pharmaceutical formulations.
The results show that acidic pH (pH = 1) strongly increases the partitioning of SAL in F127 micelles compared to neutral pH, due to the drug being in its molecular form. Fluorescence spectroscopy and small-angle neutron scattering show that free and SAL-loaded F127 micelles transition to cylindrical micelles at pH = 1 and high temperatures (37 °C). Micelles loaded with SAL are disrupted by DIMEB to a higher extent than at pH = 7 at physiological temperature. This study reveals that F127 could be a valuable nanocarrier for intestine controlled release of SAL. Taken together, our results highlight the importance of water in the structure of the micelles and their interaction with DIMEB, and bring precious insights into the mechanisms that regulate drug loading and release in complex formulations.
L’idée directrice de ce travail de thèse était d’introduire au sein de mésophases lipidiques des molécules de β-cyclodextrine (βCD) amphiphiles obtenue par bio-estérification afin d’obtenir des nano-assemblages plurimoléculaires et multi-compartimentés combinant trois fonctions essentielles pour le transport ou la vectorisation de molécules thérapeutiques : (i) la capacité d’incorporer une substance d’intérêt par formation de complexe d’inclusion avec la cyclodextrine ; (ii) être biocompatibles et aptes à passer facilement les barrières biologiques ; (iii) pouvoir co-incorporer une seconde substance d’intérêt, hydrophile ou hydrophobe, dont l’action biologique soit différente de celle assurée par la première substance. L’ensemble des travaux ont porté sur le dérivé βCD-C10 polysubstitué en face secondaire par des chaînes hydrocarbonées en C10 avec un degré moyen de substitution de 7,5. L’association de ce dérivé avec trois catégories de lipides a été envisagée : des tensioactifs micellaires non-ioniques (Brij 98, Polysorbate 80, n-dodécyl-β-D-maltoside), un lipide lyotrope non lamellaire formant des mésophases de type cubique bicontinue (monooléine), un phospholipide s’auto-organisant en bicouches propices à l’obtention de vésicules (dimyristoyl phosphatidylcholine). Selon une démarche principalement physico-chimique, différentes techniques ont été mises en œuvre pour caractériser les systèmes mixtes lipide/βCD-C10 aux échelles moléculaire et supramoléculaire : diffusion-diffraction des rayons X, calorimétrie différentielle, spectrophotométrie d’absorption UV-visible, spectroscopie de fluorescence, diffusion de la lumière statique (turbidimétrie) ou quasi-élastique, microscopie optique et microscopie électronique par cryo-transmission. L’ensemble des résultats démontrent que le dérivé βCD-C10 forme spontanément ou selon un protocole très simple, des assemblages plurimoléculaires mixtes avec les trois catégories de lipides, assemblages dont la topologie dépend de la structure chimique du lipide et du taux de cyclodextrine amphiphile incorporé (tubules, vésicules uni- ou oligolamellaires, cubosomes). Ces assemblages sont stables et capables d’incorporer une substance hôte hydrophobe, notamment les vésicules mixtes tensioactif non-ionique/ βCD-C10 et les cubosomes mixtes monooléine/P80/ βCD-C10.
L’utilisation de la mousse en récupération assistée du pétrole (Enhanced Oil Recovery, EOR) présente un avantage indéniable par rapport à l’injection du gaz seul pour pallier les problèmes de ségrégation gravitaire et de digitations visqueuses. Son utilisation systématique en ingénierie du réservoir nécessite des connaissances plus approfondies sur son comportement en milieu poreux. La littérature montre deux types d’approches expérimentales basées soit sur des études pétrophysiques effectuées sur des systèmes poreux 3D et basées sur des mesures de pressions intégrées sur l’ensemble du milieu poreux, soit sur des études micro-fluidiques qui permettent une visualisation directe de l’écoulement mais qui sont limitées à des systèmes modèles dans des géométries à 1 ou 2 dimensions. L’objectif de cette thèse est de faire le pont entre ces deux approches. La stratégie proposée consiste à caractériser in situ l’écoulement de la mousse dans des milieux poreux 3D à différentes échelles, en utilisant des techniques complémentaires permettant d’accéder à une large gamme de résolutions spatiale et temporelle. Un environnement instrumenté donnant accès aux mesures pétro-physiques classiques a été développé puis couplé à différentes cellules d’observation conçues spécifiquement pour chaque instrument de caractérisation. Dans un premier temps, un scanner X a été utilisé pour décrire et visualiser les écoulements de la mousse à l’échelle de la carotte. La rhéologie de la mousse à cette échelle a pu être étudiée en fonction des conditions d’injections comme la vitesse interstitielle du gaz et la qualité de mousse. Dans un deuxième temps, la technique de diffusion des neutrons aux petits angles (SANS) a permis de sonder la texture de la mousse en écoulement sur trois ordres de grandeurs en taille. Des informations in situ sur la texture de la mousse en écoulement (taille et densité des bulles et des lamelles) ont pu être mesurées pour différentes qualités de mousse puis en fonction de la distance au point d’injection. Une comparaison avec les caractéristiques géométriques du milieu poreux a également été effectuée. Dans un troisième temps, la micro-tomographie X rapide haute résolution sur Synchrotron a été utilisée pour visualiser la mousse en écoulement à l’échelle du pore. Cette technique a permis de confirmer de visu certaines caractéristiques de la mousse mesurées par SANS et de décrire en sus les effets d’intermittence du piégeage de la mousse. Cette étude constitue une étape importante de la caractérisation multi-échelle de l’écoulement des mousses en milieux poreux 3D et apporte des éléments de réponse à certaines hypothèses admises.
The discovery of ordered mesoporous materials in 1992 by Mobil Oil Corporation scientists has opened great opportunities for new applications in many emerging fields such as heterogeneous catalysis, biocatalysis, energy conversion, biosensors, photocatalytic devices and environmental technologies. Porous materials are grouped by the International Union of Pure and Applied Chemistry (IUPAC) into three classes according to their pore diameter: microporous (< 2 nm), mesoporous (2–50 nm) and macroporous (> 50 nm). One of the most versatile methods for the preparation of those materials is the soft template approach which combines the sol–gel process with molecular self-assembly. While the micelles formed by ionic or nonionic surfactants, as well as amphiphilic polymers, have been extensively used as templates, the supramolecular assemblies formed between cyclodextrins and block copolymers have been less investigated, despite their large chemical and structural diversity. This review article focuses mainly on nanostructured porous inorganic materials derived from cyclodextrins or cyclodextrin-based assemblies. More than 100 references are described and discussed, in which we look both at their synthesis and characterization, as well as their applications in the emerging fields of heterogeneous catalysis and photocatalysis. A special attention is paid to the evaluation of the critical parameters that need to be controlled for improving their (photo) catalytic performances.
The discovery of ordered mesoporous materials in 1992 by Mobil Oil Corporation (Mobils) scientists has opened great opportunities for new applications in many emerging fields such as heterogeneous catalysis, biocatalysis, energy conversion, biosensors, photocatalytic devices and environmental technologies. Porous materials are grouped by the International Union of Pure and Applied Chemistry (IUPAC) into three classes according to their pore diameter: microporous (< 2 nm), mesoporous (2–50 nm) and macroporous (> 50 nm). One of the most versatile methods for the preparation of these materials is the soft-template approach which combines the sol-gel process with the molecular self-assembly. Materials with monodisperse particle sizes, well-defined architectures and tunable porosity can be built by this approach using micelles formed by ionic or non-ionic surfactants, as well as amphiphilic polymers, as templates. On the other hand, the supramolecular assemblies formed between cyclodextrins and block copolymers have been less investigated in the literature for the preparation of inorganic materials or nanocomposites, despite their large chemical and structural diversity.
Using small molecules in polymer matrices is common in applications such as (i) plasticizing polymers to modify the glass transition and mechanical properties and (ii) dispersion of photoactive or electroactive small molecules in polymer matrices in organic-electronic devices Aggregation of these small molecules and phase separation leading to crystallization often cannot be morphologically controlled. If these are designed with self-assembling codes such as hydrogen bonding or aromatic interactions, their phase separation behavior would be distinctly different. This review summarizes the studies on morphologies in such situations, such as (i) sub-surface assembly in polymer matrices, (ii) controlled polymerization-induced phase separation to create polymer blends, (iii) using the polymer to direct the assembly of small molecules in liquid crystalline devices, (iv) functionalizing a polymer with self-assembling small molecules to cause organo-gelation which the polymer itself would not by itself, and (v) using such systems as templates to create porous polymer structures. Organic–inorganic hybrids using polymers as templates for nanostructures and imprinted porous membranes is an emerging area. Since self-assembly is one of the dominating area of research with respect to both small molecules, polymers as well as the combination of the two, this review summarizes the studies on the aforementioned topics. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017
Dry alginate foams intended for antibacterial photodynamic therapy (aPDT) of infected wounds were prepared. aPDT is a treatment modality involving light of appropriate wavelength, oxygen and a photosensitizer (PS) to produce radicals that attack biological targets (e.g. bacteria). The hydrophobic 5, 10, 15, 20-tetrakis(4-hydroxyphenyl)porphyrin (THPP) was chosen as a model PS and loaded into the foams. The foams contained a poloxamer (Pluronic F127) and/or ?-cyclodextrin (?CD)-derivatives, i.e. methyl?CD (M?CD), heptakis(2,6-di-O-methyl)-?CD (Hk?CD) or hydroxypropyl?CD (HP?CD).The physical characteristics of the various foams prepared and the THPP load, release and photostability were evaluated. All the foams were thin and flexible and could easily be handled and cut to fit a potential wound. Fast disintegration were observed for dry foams in water or phosphate buffered saline, while in Hanks' balanced salt solution the foams absorbed liquid without losing their integrity. All the foams had a similar THPP load of 0.12-0.13% w/w. The presence of ?CD-derivatives improved THPP release, however no differences were observed between the different types of ?CD-derivatives evaluated. THPP loaded into the foams was photolabile, which induced a color change combined with fading. Alginate foams formulated with PF127, ?CD-derivatives and THPP demonstrated applicability as delivery vehicles for PSs in aPDT of wounds.
Binary and ternary systems comprising the photosensitizer 5, 10, 15, 20-tetrakis(4-hydroxyphenyl)porphyrin (THPP), poloxamer 407 and the β-cyclodextrin (βCD)-derivatives hydroxypropylβCD (HPβCD), methylβCD (MβCD) and heptakisβCD (HkβCD) were prepared. Solubility studies, absorption and fluorescence measurements, nano differential scanning calorimetry and particle size measurements were performed to evaluate the binary and ternary systems. The drug/CD inclusion complexes were characterized by a high apparent stability constant (K1:1: 10⁴-10⁵) and a low complexation efficiency (CE: 0.0056-0.0145). The THPP solubility increased by a factor 850 in binary systems containing MβCD and by a factor 10 000 in ternary systems of the same CD. The spectroscopic characteristics of THPP were slightly changed in the binary and ternary systems. The photosensitizer remained as a CD-inclusion complex in ternary systems containing MβCD while it seemed to be located in the poloxamer phase in the presence of HkβCD or HPβCD. The critical micelle concentration (cmc) of the poloxamer 407 was apparently reduced in the presence of THPP. HkβCD interfered with the micellization process both in the absence and to a certain extent, also in the presence of THPP. Selection of the appropriate βCD-derivative makes it possible to prepare ternary systems tailor made for a certain formulation principle or medical treatment.
Polymers and small molecules are used together in a number of applications. The small molecule may be used to modify polymer properties, or the polymer could be a vehicle to just hold the functional small molecule. In the former category, the plasticization of polymers is well known. The small molecules, typically phthalates, are blended with the polymers to tailor the glass transition temperature and enable processing at lower temperatures. The polymer simply holds the small molecule as a dispersion. This chapter discusses the behavior of the small molecules in such films. With the organic photoreceptors that are used in photocopiers and printers, the charge transport molecule (CTM), usually of the tritolylamine (TTA) type is dispersed in a polycarbonate matrix by solution coating. Phase separation has been used advantageously in a number of applications. Polymerization-induced phase separation (PIPS) is a technique that was developed a couple of decades ago, and has been adapted to a few technologies.
We demonstrated a new strategy for efficient preparation of polypseudorotaxanes (PpRXs) and polyrotaxanes (PRXs) with cyclodextrin derivatives, 2,6-di-O-methyl-cyclodextrins (DM-CyDs), by utilizing the cloud points of DM-CyDs. DM-α-CyD and DM-β-CyD formed PpRXs with polyethylene glycol (PEG) and polypropylene glycol (PPG) in water at >50 °C and >35 °C, respectively, but did not at room temperature. Meanwhile, randomly methylated β-CyD (RM-β-CyD) and 2,3,6-tri-O-methyl-β-CyD (TM-β-CyD) did not form PpRX with PPG at higher temperature. The driving force of thermoresponsive formation of DM-CyD PpRXs was derived from hydrophobic interaction of methyl groups and a hydrogen bond of hydroxyl groups formed by adjacent DM-CyD molecules. Furthermore, in one pot, DM-CyD PRXs were synthesized by capping the PpRXs with bulky ends in high yields.
Micelles of the triblock copolymer Pluronic F127 can encapsulate drugs with various chemical structures and their architecture has been studied by small-angle neutron scattering (SANS). Interaction with a derivative of β-cyclodextrin, namely, heptakis(2,6-di-O- methyl)-β-cyclodextrin (DIMEB), induces a complete break-up of the micelles, providing a mechanism for drug release. In the presence of drugs partitioned within the micelles, competitive interactions between polymer, drug and cyclodextrin lead to a modulation of the micellar rupture, depending on the nature of the drug and the exact composition of the ternary system. These interactions can be further adjusted by temperature and pH. While the most widely accepted mechanism for the interaction between Pluronics and cyclodextrins is through polypseudorotaxane (PR) formation, involving the threading of β-CD on the polymer backbone, time-resolved SANS experiments show that de-micellisation takes place in less than 100 ms, thus unambiguously ruling out an inclusion complex between the cyclodextrin and the polymer chains.
Inclusion complexes between cyclodextrins (CDs) and polymers - so-called pseudopolyrotaxanes (PPR) - are at the origin of fascinating supramolecular structures, which are finding increasing uses in biomedical and technological fields. In this work, we explore the complexation of a range of cyclodextrins with Tetronic T1307, a four-arm block-copolymer of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) with a pH-responsive central ethylene diamine spacer, and its impact on micellisation and sol-gel transition. At low concentrations, small-angle neutron scattering (SANS) combined to dynamic light scattering (DLS) measurements show the presence of spherical micelles with a highly hydrated shell and a dehydrated core. Increasing the temperature leads to more compact micelles and larger aggregation numbers, while acidic conditions induce a shrinking of the micelles, with fewer unimers per micelle and a more hydrated corona. At high concentrations, T1307 undergoes a sol-gel transition, which is suppressed at pH below pKa,1 (4.6). SANS data analysis reveals that the gels result from a random packing of the micelles, which have an increasing aggregation number and increasingly dehydrated shell and hydrated core. Native CDs (α, β, γ-CD) can complex T1307, resulting in the precipitation of a PPR. Instead, modified CDs compete with micellisation, to an extent that is critically dependent on the nature of the substitution. 1H and ROESY NMR combined to SANS demonstrate that di-methylated β-CD can thread onto the polymer, preferentially binding to the PO units, thus hindering self-aggregation by solubilizing the hydrophobic block. The various CDs are able to modulate the onset of gelation and the extent of the gel phase, and the effect correlates with the ability of the CDs to disrupt the micelles, with the exception of a sulfated sodium salt of β-CD, which, while not affecting the CMC or CMT, is able to fully suppress the gel phase.
Inclusion complexes between cyclodextrins and polymers - so-called pseudopolyrotaxanes (PPR) - are at the origin of fascinating supramolecular structures, which are finding increasing uses in biomedical and technological fields. Here we explore the impact of both native and a range of modified cyclodextrins (CD) on the self-assembly of X-shaped poly(ethylene oxide)-poly(propylene oxide) block copolymers, so-called Tetronics or poloxamines, by focusing on T904 (Mw 6.700). The effects are markedly dependent on the type and arrangement of the substituents on the macrocycle. While native CDs drive the formation of a solid PPR, most substituted CDs induce micellar break-up, with dimethylated β-CD (DIMEB) having the strongest impact and randomly substituted CDs a much weaker disruptive effect. Using native α-CD as a 'molecular trap', we perform competitive binding experiments - where two types of CDs thread together onto the polymer chains - to establish that DIMEB indeed has the highest propensity to form an inclusion complex with the polymer, while hydroxypropylated CDs do not thread . 1D 1H-NMR and ROESY experiments confirm the formation of a soluble PPR with DIMEB in which the CD binds preferentially to the PO units, thus providing the drive for the observed de-micellisation. A combination of Dynamic Light Scattering (DLS) and Small-Angle Neutron Scattering (SANS) is used to extract detailed structural parameters on the micelles. A binding model is proposed, which exploits the chemical shifts of selected protons from the CD in conjunction with the Hill equation, to prove that the formation of the PPR is a negatively cooperative process, in which threaded DIMEBs hamper the entrance of subsequent macrocycles.
Multiferroics ErMn2O5 nanorods have been synthesized via surfactant-templated hydrothermal route. Environmentally friendly natural surfactant (arabic gum) has been utilized as a template to prepare ErMn2O5 nanorods with a controllable morphology and size (i.e., nanorods with various lengths and basically invariable diameter). ErMn2O5 nanorods show strong size-dependent magnetic properties that correlate with: (a) a critical length for magnetization, and (b) recognizable divagation between FC and ZFC curves at low temperature. The former could be ascribed to the competition between surface strain and uncompensated spin at the surface, and the latter to Er antiferromagnetic ordering.
Micellar to gel phase transition in the aqueous triblock copolymer F127 solutions occurs at higher temperatures in the presence of cyclodextrin and the temperature range corresponding to the gel phase is contracted. These features were observed by dynamic rheometry and the tube inversion method. We investigated further the behaviours of various molecular probes in Pluronic F127 solutions in the absence and in the presence of hydroxypropyl-β-cyclodextrin (HPB) as a function of temperature by continuous wave electron paramagnetic resonance (cw-EPR), Electron Spin Echo Envelope Modulation (ESEEM) and fluorescence spectroscopy, to correlate the observed macroscopic and microscopic changes. The use of molecular probes with different structural particularities allowed the targeting of different regions of F127 micelles which are inhomogeneous at the nanoscale level and the elucidation of the mode in which HPB influences the phase transition in such systems. Dansyl-TEMPO (DT), with a dual character (paramagnetic and fluorescent), spin labelled cyclodextrin (MTCYC), spin labelled Pluronics – L62NO and F127NO, dansyl β-CD (D-β-CD) and pyrene were employed as molecular probes. Both cw-EPR and fluorescence measurements revealed that molecular probes with a more hydrophobic character are more sensitive to phase transition occurring in the studied systems.
Controlling interactions at the supramolecular level is of importance for the preparation by template directed synthesis of mesoporous materials with tailored pore structures. Herein we investigate the effect of randomly methylated β-cyclodextrin on the association behavior of the amphiphilic triblock copolymer Pluronic P123 in aqueous solution. Surface tension, dynamic light scattering, and viscosity measurements provide quantitative evidence that, when the cyclodextrin is added in controlled amounts to the copolymer, it strongly impacts the micellar growth rate. The property of randomly methylated β-cyclodextrin to act as a micelle expander has been further exploited to generate a series of mesoporous γ-alumina by a sol−gel method. The resulting materials subjected to calcination at 500 °C exhibit high surface area (354−382 m2/g), tunable pore size (14.8−19.3 nm), and very large pore volume (1.37−1.97 cm3/g), making them excellent candidates for applications in the fields of adsorption and heterogeneous catalysis.
Previous studies demonstrated that hydrophobic proteins could be PEGylated in organic phase rather than water phase. It is still not known what the difference is for a hydrophilic protein's PEGylation in these two different phases. In this study, granulocyte colony stimulating factor (G-CSF) was dissolved in neat dimethyl sulfoxide (DMSO) and was PEGylated. In comparison with the PEGylation in water solution, the PEGylation degree in the organic solvent increased by 33% and 42% for PEG-maleimide (MAL-PEG) and PEG-succinimidyl carbonate (SC-PEG) respectively. Structure analysis revealed that the protein was unfolded in DMSO, which could make the PEGylated sites of G-CSF easily accessible. The hydrolysis half-life in water solution was 40min and 9h for SC-PEG and MAL-PEG respectively. However, in DMSO solvent, PEGs were very stable and no hydrolysis could be detected. Stopped-flow demonstrated that the conjugation speed of G-CSF by MAL-PEG and SC-PEG in DMSO were 1.6×10(4) and 2×10(2) times faster than those in aqueous solution. The remarkable acceleration could mainly be attributed to an increase of protein nucleophilicity in DMSO. The results of this study could be referential to industrial application where the cost of PEG reagents and the speed of reaction on large scale are very important.
A coumarin-methyl-β-cyclodextrin (CCA-MCD) was synthesised. Fluorescence studies showed that CCA-MCD could successfully sense hydroxyl radicals (·OH) in water and it had a specific fluorescence response to ·OH over other free radicals. Further study showed that it could monitor intracellular ·OH as well. These findings suggest that CCA-MCD can be used as a cell-permeable fluorescence sensor to study the function of ·OH in biological processes.
We report the influence of five beta-cyclodextrin (beta-CD) derivatives, namely: randomly methylated-beta-cyclodextrin (MBCD), heptakis (2,6-di-O-methyl)-beta-cyclodextrin (DIMEB), heptakis (2,3,6-tri-O-methyl)-beta-cyclodextrin (TRIMEB), 2-hydroxyethyl-beta-cyclodextrin (HEBCD) and 2-hydroxypropyl-beta-cyclodextrin (HPBCD), on the self-assembly of mixtures of non-ionic surfactants: polyoxyethylene cholesteryl ether (ChEO10) and monocaprylin (MCL). Mixtures of ChEO10/MCL in water form highly viscoelastic wormlike micelle solutions (WLM) over a range of concentrations; herein the composition was fixed at 10 wt% ChEO10/3 wt% MCL. The addition of methylated beta-CDs (MBCD, DIMEB, TRIMEB) induced a substantial disruption of the solid-like viscoelastic behaviour, as shown from a loss of the Maxwell behaviour, a large reduction in G' and G" in oscillatory frequency-sweep measurements, and a drop of the viscosity. The disruption increased with the degree of substitution, following: MBCD < DIMEB < TRIMEB. Cryo-TEM images confirmed a loss of the WLM networks, revealing short rods and disc-like aggregates, which were corroborated by small-angle neutron scattering (SANS) measurements. Critical aggregation concentrations (CAC), measured by fluorescence spectroscopy, increased in the presence of DIMEB for both ChEO10 and MCL, suggesting the existence of interactions between methylated beta-CDs and both surfactants involved in WLM formation. Instead, hydroxyl-beta-CDs had a very different effect on the WLM. HPBCD only slightly reduced the solid-like behaviour, without suppressing it. Quite remarkably, the addition of HEBCD reinforced the solid-like characteristics and also increased the viscosity 10-fold. Cryo-TEM images confirmed the subsistence of WLM in ChEO10/MCL/HEBCD solutions, while SANS data revealed a slight elongation and thickening of the worms, and an increase of associated water molecules. CAC data showed that HPBCD had little effect on either surfactant, while HEBCD strongly affected the CAC of MCL and only slightly ChEO10. For both DIMEB and HEBCD, time-resolved SANS measurements showed that morphology changes underlying these macroscopic changes occur in less than 100 ms.
Aqueous mixtures of γ-cyclodextrin (γ-CD) and the thermosensitive cationic diblock copolymer poly(N-isopropylacrylamide)-b-poly(3-acrylamidopropyl)trimethylammonium chloride (PNIPAAM24-b-PAMPTAM(+)9) or the PNIPAAM homopolymer PNIPAAM47 have been investigated using various experimental methods. Solid γ-CD–polymer inclusion complexes (pseudopolyrotaxanes) form at ambient temperatures in fairly concentrated CD solutions. The NMR measurements showed that the stoichiometry of the inclusion complexes is close to two NIPAAM units per CD molecule. The cationic block of the copolymer is not incorporated into the CD cavity. Synchrotron radiation X-ray diffraction spectra of the solid inclusion complexes indicate a compact columnar structure of CD molecules threaded onto the PNIPAAM chains. In water, square-shaped cyclodextrin aggregates were found to co-exist with single cyclodextrin molecules. In mixed solutions of γ-CD and PNIPAAM24-b-PAMPTAM(+)9 these aggregates disintegrate with time as inclusion complexes are formed and the kinetics was studied using time-resolved static and dynamic light scattering and cryo-TEM. Steady-state fluorescence spectroscopy measurements reveal that the CD molecules dethread from the PNIPAAM chains upon increasing the temperature to 40 °C, which is above the lower critical solution temperature of PNIPAAM.
The interaction of B-dextrins with poly(ethylene oxide)-poly(propylene oxide) block copolymers (these differed in composition, molecular mass, and the number and position of blocks in the macromolecule) resulted in new crystalline complexes showing a high degree of crystallinity and a narrow size distribution of the crystallites. The melting temperatures of the complexes varied from 126 to 136°C, thus being intermediate between the melting points of the individual components. The melting temperature of the complexes decreased with an increase in propylene oxide content in the copolymer. The determined composition of the complex satisfactorily agreed with the one calculated on the following assumption: that only the propylene oxide block of the copolymer was involved in complexation with the stoichiometry of one cyclodextrin molecule per two propylene oxide monomeric units. We suggest a model for the complex of the copolymer with B-cyclodextrin, which takes into account both the inclusion complex formation and the hydrogen bonding between components.
Water-insoluble inclusion complexes of α-, β-, and γ-cyclodextrins with triblock copolymers of ethylene and propylene oxides (proxanols) were studied. It was found that, depending on the experimental conditions, the interaction of α-and β-cyclodextrins leads to the formation of either symmetric copolymers with molecular "necklaces" as terminal blocks, or nonsymmetric copolymers composed of three different blocks. Use of the poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) copolymer (as the "guest" molecule) and γ-cyclodextrin (as the "host") led to the formation of new double-chain inclusion complexes. All the obtained complexes appeared as crystalline compounds. The crystal lattice parameters of the complexes are determined primarily by the packing of the molecular necklaces formed by a given cyclodextrin and a proxanol block with complementary dimensions.
In one-photon dissociation of propionyl chloride at 248 nm, time-resolved Fourier-transform infrared emission spectroscopy is used to detect the fragments of HCl and CO in the presence of Ar. The inert gas Ar plays a role to enhance the internal conversion. The time-dependence of high-resolution HCl spectra yields a bimodal rotational distribution in the early stage. The total rotational and vibrational energy partitioned in HCl are evaluated to be 1.7 ± 0.3 and 8.8 ± 1.9 kcal/mol, respectively. The CO appearance indicates that HCl may be eliminated through a five-center mechanism accompanied with three-body dissociation of C2H2, HCl, and CO. A four-center mechanism forming HCl and CH3CHCO also contributes to the HCl fragment with a feature of rotational bimodality. However, the probability for the HCl contribution from the hot Cl reaction is negligible. The reaction with CH4 is carried out to evaluate the HCl and Cl elimination rate constants.
A polyrotaxane, in which many β-cyclodextrins (β-CDs) are threaded onto a triblock copolymer of poly(ethylene glycol) (PEG) and poly(propylene glycol) (PPG) capped with fluorescein-4-isothiocyanate (FITC), was synthesized as a model of stimuli-responsive molecular assemblies for nanoscale devices. Coupling of FITC with the terminal amino groups in the polypseudorotaxane was performed in DMF at 5 °C. Under these conditions, a side reaction between the hydroxyl groups of β-CD and FITC was prevented. The interaction of the β-CDs with terminal FITC moieties in the polyrotaxane was significantly observed at low temperature. However, the interaction of the β-CDs with the PPG segment was observed with increasing temperature. On the basis of these results, it is concluded that the majority of the β-CDs move toward the PPG segment with increasing temperature although some β-CDs may reside on the PEG segments.
This review explores the advances in stimuli-responsive polymeric inclusion complexes, comprising of cyclodextrins, in aqueous media. Cyclodextrin complexation allows these polymeric systems to possess tailored physical properties that permit them to form novel supramolecular structures. By including and combining stimuli-responsive characteristics, these special systems can transform into various morphologies when exposed to different kinds of external stimuli. A wide variety of these stimuli-responsive polyrotaxanes and functionalized cyclodextrinpolymers that possess interesting supramolecular characteristics are discussed, with specific focus on pH-, temperature-, photo- and redox- sensitive systems. These unusual polymer/cyclodextrin systems provide a basis for many useful applications, such as drug delivery, environmentally friendly coatings, personal home care products, separation processes, food processing, and microelectronics.
The associative structures of four β-cyclodextrins (βCD) derivatives with triblock copolymers of polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO) (Pluronics) were investigated by small-angle neutron scattering (SANS), wide-angle X-ray scattering (WAXS) and Fourier transform infrared spectroscopy (FTIR). As shown in a previous study (J. Joseph, C. A. Dreiss, T. Cosgrove, and J. S. Pedersen, Langmuir, 2007, 23, 460–466), the addition of increasing amounts of heptakis(2,6-di-O-methyl)-βCD (hep2,6-βCD) promoted a progressive break-up of the Pluronic micelles, while three other derivatives studied, namely, heptakis(2,3,6-tri-O-methyl)-βCD, 2-hydroxyethyl-βCD and 2-hydroxypropyl-βCD, did not lead to any visible change. This is attributed to the capacity of βCD to form pseudopolyrotaxanes with the PPO block and decrease its hydrophobicity, which is highly dependent on the availability of free hydroxylgroups on the βCD. Since the gradual de-assembly of micelles could be envisaged as a possible trigger to release the drug encapsulated in the micelles, the interaction of two local anaesthetics, lidocaine and benzocaine, with the Pluronics micelles were investigated. Fitting the SANS data with a paracrystalline model showed that the encapsulation of a drug inside the micellar core led to an increase in micellar size as well as the appearance of long-range order in the solutions. Finally, the competitive interactions of βCD and drug with the polymeric micelles were studied. The presence of a drug inside the micelles reduced the disruptive action of hep2,6-βCD, which is attributed to both the capacity of the drug to hold the micelles together and to the formation of an inclusion complex between βCD and the drug.
Interactions between 3H-indole derivatives, their cations and anions, and microheterogeneous environments like micelles and vesicles have been studied extensively in our laboratory recently. We report herein the interactions of 2-(p-aminophenyl)-3,3-dimethyl-5-cyano-3H-indole (1) and 2-[p-(dimethylamino)phenyl]-3,3-dimethyl-5-cyano-3H-indole (2) with aqueous solutions of β-cyclodextrin (β-CD), studied by absorption and fluorescence steady-state and time-resolved measurements. The stoichiometries of the cyclodextrin:guest inclusion complexes have been determined by steady-state fluorescence measurements. The data reveal that two types of complexes, i.e., 1:1 and 2:1 types are formed. Thermodynamic parameters are calculated at six different temperatures. Spectral characteristics, bandwidths, and photophysical parameters indicate that molecule 2 is better protected against hydrophilic interactions. Protonation reactions carried out at different concentrations of β-CD show that the protonation is inhibited at the indolic nitrogen, contrary to what was observed in other microheterogeneous media. Time-resolved measurements and global analysis of the results are best described by a discrete triple exponential decay law clearly indicating that the guest molecules experience three different environments in aqueous solutions: bulk water and a stepwise 1:1 and 2:1 (β-cyclodextrin:guest) inclusion complexation. The effective polarity of the cyclodextrin cavity is equivalent with the polarity of an 80:20 methanol−water mixture at the β-CD rim where the indolic (tertiary) nitrogen is likely to be located near the “alcoholic” secondary rim of the macrocycle.
β- and γ-cyclodextrin form complexes with poly(propylene glycol) of various molecular weights to give crystalline compounds in high yields, although they do not form complexes with propylene glycol, dipropylene glycol, nor tripropylene glycol; α-cyclodextrin does not form complexes with poly(propylene glycol).
The absorption curves of methyl orange (MO) and analogous p-aminophenylazobenzenes in organic and aqueous organic solvents are shown to consist of two severely overlapping bands. The curves have been resolved into two skewed component bands using a regression method. The blue shift of the absorption maximum obtained when organic solvents are added to aqueous solutions of MO, or when MO is bound to bovine serum albumin or a surfactant micelle, is the result of a change in relative intensities of the component bands. The low-frequency component is assigned to a π1 → π1* transition of a solvate in which there is specific hydrogen-bonding interaction between solvent and the azo nitrogens, and the high-frequency component to a π1 → π1* transition of a solvate in which the interaction is absent. The low-frequency component is favored by aqueous solvent compositions and by low temperatures. The free energies of interconversion of the species in various hydrogen-bonding solvents are correlated by the solvent surface tension but not by the dielectric constant. The results show that the shift in absorption maximum accompanying binding to a protein or micelle should be interpreted as a shift in an equilibrium rather than as a shift in transition energy.
Cyclodextrin (CD) and copolymers of polyethylene oxide (PEO)-b- polypropylene oxide (PPO)-bpolyethylene oxide (PEO) (pluronics) form inclusion complexes (ICs) in water. A solution of native unmodified β-CD was mixed with a dilute solution of pluronic F-68 at 70 °C. The temperature was then quickly cooled down below the critical micellization temperature (CMT) of the triblock-copolymer. The mixture was left ageing at controlled temperature until turbidity, opalescence and finally sedimentation occurred. The self-organization behaviour of the system was investigated by small angle neutron scattering (SANS) in D2O. At high temperature the formation of stable, β-CD-swollen micelles was observed. ICs were formed while the mixture was thermally quenched. Their subsequent aggregation was studied by SANS, and the resulting structures were observed by atomic force microscopy (AFM) after film deposition. With time, we evidenced the formation of thin platelets (17 nm) having large planar dimensions (about 1 mm at 20 °C to 4 mm at 40 °C) and a crystallographic angle of 105.4°. Fitting the SANS data, a model was proposed where the growth of a platelet occurred through association of IC bundles in a characteristic time of 190 min. Each bundle (2.4 nm in radius and 17 nm in length) of well-organized IC molecules is formed in a characteristic time of 17 min at 20 °C. The platelets are original because of their crystalline nature with well-defined angles, and their very flat and rigid shape. Moreover they form effortlessly through self-assembling in water.
The absorption and fluorescence spectra of a highly fluorescent laser dye, Nile red, were investigated in nematic solvents and isotropic liquids as a function of the solvent polarity and type. The interaction of the dye with the anisotropic surrounding and with that of the isotropic solvents was investigated and compared using optical spectroscopy. The spectral behavior of the cationic oxazine dye, Nile blue, was also investigated in anisotropic and isotropic environments for comparison. The spectral shifts were correlated by the solvent polarity and nature. The electro-optical effect of the guest–host systems was also investigated in an electro-optical system using polarized spectroscopic method and the dichroic ratios R and degree of anisotropies S of these dyes in the liquid crystalline hosts were investigated.
Using pyrene and homologous alkyl derivatives of fluorescein as fluorescent probes, this work examines the partitioning coefficients of hydrophobic solutes in aqueous dispersions of Pluronic block copolymers (poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide)). An incremental approach is developed, allowing measurement of the free energy of transfer of a methylene group from aqueous media into the micelles. Effects of variation of length of the ethylene oxide (EO) and the propylene oxide (PO) blocks in Pluronic molecules on the partitioning characteristics of the solutes are established. A simple reciprocal relationship between partitioning coefficients of the solute and critical micellization concentration is demonstrated.
Aqueous solutions of α-cyclodextrin (α-CD) and polyethylene glycol (PEG) form interesting complexes, where several α-CD units are penetrated by the linear polymeric PEG chain and produce a so-called “polyrotaxane”. This supramolecular structure is stabilized by strong interactions between the α-CD hydrophobic internal cavity and the −CH2OCH2− moieties of PEG. When cyclodextrins have occupied the whole PEG chain, the polyrotaxanes aggregate and precipitate, forming a thick solid gel. Turbidity measurements at λ = 400 nm were used to study the threading phenomenon. The temperature of the solution and the composition of the solvent affect the formation of polyrotaxanes in a significant way. We propose a molecular model to explain the experimental findings in terms of a multistep threading process. The Gibbs free energy related to the formation of polyrotaxanes is calculated according to the transition state theory.
Small-angle neutron scattering (SANS) and rheometry were used to investigate the supramolecular structure formed by a poly(oxyethylene−oxypropylene−oxyethylene) (PEO100PPO65PEO100, Pluronic F127) copolymer in aqueous solution over a temperature range of 10−75 °C and a concentration range of 10−20 wt %. At copolymer concentrations of less than 12.5% the solutions are Newtonian fluids. Gels with an ordered structure (cubic packing of spherical micelles) are observed over a well-defined temperature window when the copolymer concentrations are greater than 17 wt %. The SANS results show that the aggregation number of the micelles is independent of temperature and concentration. Low-yield stresses, very high zero shear viscosities (106 P), and shear thinning are the major rheological characteristics of the gels. Near, but outside, the gel phase boundary the solutions are non-Newtonian (shear thinning). However, SANS shows these solutions contain domains having the same structure as that in the gel phase. The temperature window for ordered structures and non-Newtonian behavior becomes wider with increasing copolymer concentration. The degree of overlap of the micellar shells increases with increasing copolymer concentration at a given temperature and reaches a maximum at 40 °C at a fixed polymer concentration. The yield stress is due to repulsive interactions of PEO chains in the overlapped micellar shell. On the basis of SANS and rheology results, the proposed mechanism of gelation is that it involves repulsive interactions among close-packed spherical micelles, rather than aggregation or transitions in micelle morphology to rods or lamellae.
Aqueous solutions of β- or γ-cyclodextrin were found to form polypseudorotaxanes upon threading of linear hydrophobic polymers such as poly(propylene glycol) bis-2-aminopropyl ether, H3CCH(NH2)CH2(OCH2CH(CH3))nNH2 (PPG-Am2; MW ≈ 2000; nav ≈ 33), and pluronic 105, HO(CH2CH2O)34(CH2CH(CH3)O)61(CH2CH2O)34H (PLU; MW ≈ 6500). The kinetics of the threading process was determined as a function of the temperature and solvent composition (water, heavy water, and urea). When the water solution of cyclodextrin was added to the polymer's dispersion, a thick solid precipitate was promptly formed, depending on the concentration and temperature. Turbidity measurements allowed us to determine the time necessary for a complete threading of the linear polymer (the “threading time”); this parameter depends on the solution temperature and on the solvent nature. A simple kinetic model provides the activation free energy of the process, and the number of cyclodextrin molecules threaded around a single linear chain. Enthalpy, entropy, and heat capacity changes are consistent with a process ruled by hydrophobic effects.
The study addresses the effects of block composition on the self-assembly (and resulting microstructure) of amphiphilic block copolymers in the presence of selective solvents (“water” and “oil”) by examining the ternary phase behavior and structure of two copolymers, E20P70E20 and E100P70E100, having the same block architecture (ExPyEx) and P:poly(propylene oxide) middle-block size but different E:poly(ethylene oxide) end-block sizes (Pluronic P123, E20P70E20, contains 30% E and Pluronic F127, E100P70E100, 70% E). A characterization (using SAXS and deuterium NMR) of the ternary isothermal (25 °C) E20P70E20−butyl acetate−water and E20P70E20−butanol−water systems is presented first. A variety of lyotropic liquid-crystalline (LLC) phases are thermodynamically stable in the former (butyl acetate) system, both of the “normal” (oil-in-water) and of the “reverse” (water-in-oil) morphology. In the latter (butanol) system, the reverse LLC phases are not stable but are replaced by an extensive water-lean solution region under the influence of the amphiphilic character of butanol. Following the presentation of the E20P70E20−“oil”−water systems, the microstructure afforded by E20P70E20 is compared to that of E100P70E100 (Holmqvist, P.; Alexandridis, P.; Lindman, B. Macromolecules 1997, 30, 6788). In the E20P70E20 phase diagrams, the lamellar structure (of zero interfacial curvature) is the most extensive. The high-E (hydrophilic) content of E100P70E100, however, favors oil-in-water LLC structures with high interfacial curvature. The copolymer−water side of the E100P70E100 ternary phase diagrams is dominated by the micellar cubic LLC structure; for cylindrical and lamellar structures to form, significant amounts of oil are needed. No reverse LLC phases are formed by E100P70E100 in the presence of water and either butyl acetate or butanol. The normal hexagonal phase in the E100P70E100 systems occurs in approximately the same composition range as the lamellar phase in the E20P70E20 systems.
Simultaneous static and dynamic light experiments have been made on various cyclodextrins and cyclodextrin derivatives, as well as the inclusion complexes formed between different polyethylene oxide/polypropylene oxide triblock copolymers (PEO−PPO−PEO) (pluronics) and dimethyl-β-cyclodextrin (DIMEB). The inclusion complexes formed between DIMEB and pluronics are highly soluble, in contrast to the insoluble complexes formed between β-cyclodextrin and the same substances. The static light-scattering (LS) data show that approximately 11 DIMEB molecules thread onto the copolymer chains and are located on the PPO block. With the inverse structure (PPO−PEO−PPO), about seven DIMEB molecules are present in the complex. NMR measurements are used to substantiate complex formation by means of characteristic changes in the proton signals. Hydrodynamic radii obtained from the dynamic LS data at infinite dilution for the cyclodextrins correspond well with dimensions determined using X-ray methods. Inverse Laplace transformation (ILT) allowed resolution of the relaxational modes from the cyclodextrin/pluronic complex and the excess cyclodextrin. The complexes formed with the DIMEB are shown to be significantly larger than the copolymer unimers, which may be due to accentuation of steric hindrance to flexing in the PPO block. With the inverse pluronic structure, on the other hand, the complex is smaller in radius than the unimer. At temperatures above which the copolymer forms micelles, addition of DIMEB inhibits both cluster formation and micellization of the pluronics and also prevents network formation with the inverse pluronic, whereas the trimethyl analogue (TRIMEB) does not have this effect.
The kinetics of solubilization and the solubilities of neutral arenes in ionic micellar systems have been measured using phosphorescence, fluorescence, and steady-state absorption techniques. The exit rates for the arenes naphthalene, biphenyl, and l-methylnaphthalene were measured using their phosphorescence as a monitor, and found to be > 5 x 10â´sâ»Â¹. The exit rate of l-bromonaphthalene, from NaLS micelles, was determined as 2.5 x 10â´sâ»Â¹. For this molecule the entrance rate was measured as 5-8 x 10â¹Mâ»Â¹sâ»Â¹, which can be considered a representative value for other arenes. Distribution constants between arenes and micelles have been measured both at low and saturation probe to micelle ratios. The distribution constants obtained at the different probe to micelle ratios are in approximate agreement, indicating that the arenes are dispersed among the micelles consistent with a Poisson distribution. An empirical model for the solubilization process is presented which incorporates the site of solubilization of the arene and the factors which govern the exit and entrance rates from the micelle. 15 figures, 4 tables.
The effect of shear on lyotropic lamellar phases consisting of amphiphilic block copolymers was studied by in situ small-angle neutron scattering (SANS) and rheo-optics. Two different ternary systems containing a commercially available Pluronic type poly(ethylene oxide)-b-poly(propylene oxide)b-poly(ethylene oxide) block copolymer, P123 (EO20PO70EO20) or F127 (EO100PO70EO100), as well as water and butanol were investigated over a wide range of concentrations. Orientation diagrams were constructed for both ternary systems; both exhibited a parallel-to-perpendicular transition of planar lamellae and a shear-induced formation of multilamellar vesicles (also termed liposomes, onions, or spherulites). For both systems, the vesicle formation occurred at low polymer content close to the phase boundary of the lamellar region and was accompanied by shear thickening. In addition, the kinetics and temperature dependence of the parallel-to-perpendicular transition were studied.
A polyrotaxane consisting of many β-cyclodextrins (β-CDs) and a triblock copolymer of poly(ethylene glycol) (PEG) and poly(propylene glycol) (PPG) capped with bulky end-groups was synthesized as a model of stimuli-responsive supramolecules for nanoscale devices. The polyrotaxane was reversibly soluble-insoluble in water in response to temperature. This was achieved through the assembled and dispersed states of β-CDs along the block copolymer. It is considered that intermolecular hydrogen bondings of β-CDs, as well as the PEG segment length of the copoloymer, are predominant factors for regulating such thermally switchable behavior of the polyrotaxane.
Stopped-flow apparatus coupled with a large variety of detection techniques is one of the most frequently used instruments to study rapid kinetics. With the recent technical advances of small angle scattering beam-lines and more particularly in the fields of electronics and detectors, the 10 last years have seen the development of combined stopped-flow and small angle neutron or X-ray experiments. Time resolutions of the order of 10 ms for X-rays to 100 ms for neutrons allow one to follow the very early stages of the sample formation. This review presents recent applications in the fields of soft matter and biology. The different studies reveal pathways and intermediate states during phase transitions, which are of fundamental importance to understand and control the properties at equilibrium.
We have studied the spectroscopic properties of nile red (NR), a highly fluorescent laser dye, in organic solvents, binary solvent mixtures and polymers. Spectroscopic studies reveal remarkable changes in the absorption and emission band positions and intensities as a function of the polarity of the medium. Such large changes have been attributed to the twisted intramolecular charge transfer (TICT) state of the molecule in polar medium. Experimental results show that the molecule is sensitive to the polarity of its microenvironment and is an excellent probe for systems presenting restricted geometries. We have incorporated NR into thin films of poly (methyl methacrylate) (PMMA) and poly (vinyl alcohol) (PVA); it is found that the micropolarity in PVA is greater than that in PMMA; in PVA, the micropolarity corresponds to that of a binary mixture of acetonitrile and water, whereas in PMMA, the micropolarity corresponds closely to that of pure acetonitrile.
The triblock-copolymer poly(ethylene oxide)-poly(propyleneoxide)-poly(ethylene oxide) (PEO-PPO-PEO), referred to as Pluronic, is widely studied for its unique aggregation properties and its applications in drug delivery and targeting. In previous studies [Dreiss, C. A.; et al. Soft Matter 2009, 5, 1888-1896], we showed that the interaction of heptakis (2,6-di-O-methyl)-β cyclodextrin (DIMEB) with the triblock-copolymer Pluronic F127 in solutions above the CMC led to complete disruption of the polymeric micelles, while similar β cyclodextrins (βCD) derivatives, heptakis (2,3,6-tri-O-methyl)-βCD (TRIMEB), hydroxypropyl-βCD (HPBCD), and hydroxyethyl-βCD (HEBCD), did not induce micellar break-up. In this work, nuclear magnetic resonance spectroscopy experiments were used to elucidate the nature of the interactions leading to break-up and highlight differences between the four βCD derivatives studied, which could explain the very different outcome observed. Intermolecular nuclear Overhauser enhancements (NOEs) show that both DIMEB and TRIMEB interact selectively with the PPO methyl groups of F127 in a similar way. The interaction is mainly with the external methyl groups in the 6-position of the glucopyranose units of cyclodextrins. However, a weak but detectable interaction with the inner cyclodextrins protons is also observed. These interactions, both with the external surface and with the cavity of βCD, suggest the formation of a loose complex, rather than the widely invoked pseudorotaxane type of inclusion. In addition, these interactions seem to be necessary but not sufficient to induce micellar break-up. Diffusion measurements show decreased diffusivity of DIMEB in the presence of F127 to a larger extent than the other CD derivatives, thus confirming the unique behavior of DIMEB toward F127 polymer. From the diffusion coefficients, an average of 1 DIMEB molecule per 4.2 PO groups of F127 is determined for the highest concentration of DIMEB considered (11 wt % DIMEB dissolved in 5 wt % F127). Micellar break-up is complete at a concentration as low as 1 DIMEB molecule per 8.2 PO units.
A series of inclusion complexes of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-b-PPO-b-PEO) with beta-cyclodextrin (beta-CD) was prepared. Their formation, structure, and dynamics were investigated by solution two-dimensional rotating-frame Overhauser effect spectroscopy (2D ROESY) and one-dimensional (1D) and 2D solid-state (13)C NMR. The inclusion complexes between the PEO-b-PPO-b-PEO copolymers and the beta-CDs were formed in aqueous solution and detected by 2D ROESY. The high efficiency of cross polarization and spin diffusion experiments in (13)C solid-state NMR showed that the mobility of the PPO blocks dramatically decreases after beta-CD complexation, indicating that they are selectively incorporated onto the PPO blocks. The hydrophobic cavities of beta-CD restrict the PPO block mobility, which is evidence of the formation of inclusion complexes in the solid state. The 2D wide-line separation NMR experiments suggested that beta-CDs only thread onto the PPO blocks while forming the inclusion complexes. The stoichiometry of inclusion complexes was studied using (1)H NMR, and a 3:1 (PO unit to beta-CD) was found for all inclusion complexes, which indicated that the number of threaded beta-CDs was only dependent on the molecular weight of the PPO blocks. 1D wide angle x-ray diffraction studies demonstrated that the beta-CD in the inclusion complex formed a channel-like structure that is different from the pure beta-CD crystal structure.
The associative structures between F127 Pluronic micelles and four drugs, namely, lidocaine (LD), pentobarbital sodium salt (PB), sodium naproxen (NP), and sodium salicylate (SAL), were studied by small-angle neutron scattering (SANS). Different outcomes for the micellar aggregates are observed, which are dependent on the chemical nature of the drug and the presence of charge or otherwise: the micelles grow with LD, are hardly modified with PB, and decrease in size with both NP and SAL. The partition coefficient, determined by fluorescence spectroscopy, is directly correlated to the amount of charge, following NP approximately SAL < PB < LD. All drugs are found to lie at the interfacial layer, with a slightly deeper localization of LD and more superficial for PB. All drugs can form inclusion complexes with heptakis(2,6-di-O-methyl) beta-cyclodextrin (hep2,6 beta-CD). Hep2,6 beta-CD, as shown in previous studies (Joseph, J.; Dreiss, C. A.; Cosgrove, T. Langmuir, 2008, 24, 10005-10010; Dreiss, C. A.; Nwabunwanne, E.; Liu, R.; Brooks, N. J. Soft Matter, 2009, 5, 1888-1896), is also able to form a complex with F127, resulting in micellar breakup. In the ternary mixtures, a fine balance of forces is involved, which results in drastic micellar changes, as observed from the SANS patterns. Depending on the ratio of drug, polymer, and hep2,6 beta-CD and the nature of the interactions (which is directly linked to the drug chemical structure), the presence of drug either hinders micellar breakup by beta-CD (at high enough concentration of LD or PB) or leads to micellar growth (NP). These effects are mainly attributed to a preferential drug/beta-CD interaction (except for PB), which, at least in the conditions studied here, explains the higher beta-CD concentration needed for micellar breakup to occur.
This review describes the synthesis, properties, and, in particular, biomedical and pharmaceutical applications of an upcoming class of polymeric networks and assemblies based on cyclodextrins (CDs). CDs are cyclic oligosaccharides composed of alpha-1,4-coupled d-glucose units, which contain a hydrophobic internal cavity that can act as a host for various, generally lipophilic, guest molecules. Because of this unique physicochemical property, commonly referred to as inclusion complex formation, CDs have often been used to design polymeric materials, such as hydrogels and nanoparticles. Polymeric systems based on CDs exhibit unique characteristics in terms of mechanical properties, stimuli-responsiveness, and drug release characteristics. In this contribution, first, an outline is given of covalently cross-linked polymeric networks in which CD moieties were structurally incorporated to modulate the network strength as well as the complexation and release of low molecular weight drugs. Second, physically assembled polymeric systems are discussed, of which the formation is accomplished by inclusion complexes between polymer-conjugated CDs and various guest molecule-derivatized polymers. Due to their physical nature, these polymeric systems are sensitive to external stimuli, such as temperature changes, shear forces and the presence of competing CD-binding molecules, which can be exploited to use these systems as injectable, in situ gelling devices. In recent years, many interesting CD-containing polymeric systems have been described in literature. These systems have to be optimized and extensively evaluated in preclinical studies concerning their safety and efficacy, making future clinical applications of these materials in the biomedical and pharmaceutical field feasible.
A new category of mechanized nanoparticles, consisting of a hollow mesoporous silica spherical framework controlled by a supramolecular system containing the alpha-cyclodextrin (alpha-CD) ring on a stalk that is tethered to the pore openings on the nanosphere, is synthesized and tested. Construction of the nanovalve relies on the hydrogen-bonding interaction between alpha-CD and the stalk. The stalk is bonded to the nanoparticle chemically and contains an anilino group that is located on the end of the linker molecule that is closest to the pore entrance. When the alpha-CD ring is complexed with the stalk at neutral pH, the bulky cyclic component is located near the pore openings, thereby blocking departure of cargo molecules that were loaded in the nanopores and hollow interior of the particle. Protonation of the nitrogen atoms at lower pH causes the binding affinity to decrease, releasing the alpha-CD and allowing the cargo molecules to escape. The properties of this newly designed pH-responsive nanovalve are compared to those of conventional mesoporous silica nanoparticles. The on-command pH-activated release is measured using luminescence spectroscopy. The effect of different stalk lengths and pH conditions on the release of fluorescent dye cargo molecules is measured.
The interactions between poloxamer 407 (Pluronic F127, PF127) and two hydrophilic derivatives of beta-cyclodextrin, i.e., hydroxypropyl-beta-cyclodextrin (HPbetaCD; molar substitution (MS) 0.65) and methylated-beta-cyclodextrin (MbetaCD; MS 0.57), were characterized by means of surface tension measurements, pi-A isotherms, isoperibol microcalorimetry, 1H NMR, and rheometry. An effective complexation of poloxamer with the two CDs was evidenced as a change in the surface pressure of the pi-A isotherm of PF127 on a subphase of CD solution, with a positive excess being observed at the expanded region and a negative excess at the collapsed region. Such changes indicated that when the CD lies with the main axis perpendicular to the interface at low pressure no complexation occurs, but as the pressure increases and the CDs eventually change their arrangement to be with the main axis parallel to the interface, the amphiphilic copolymer can form polypseudorotaxanes. Addition of CDs to PF127 micellar solutions led to the exothermic rupture of micelles, a shift in the cmc toward higher values, changes in the chemical shifts of H3, H4, and H5 of MbetaCD and of the methyl groups of PF127, and an increase in the gel temperature. The interaction was stronger between poloxamer and MbetaCD, compared to HPbetaCD, with the stoichiometry of the polypseudorotaxanes being preferably ca. 1:20 in both cases. SEM images revealed formation of nanorods of stacked polypseudorotaxanes. Complexation with a high affinity constant between unimers and CDs in bulk solution was also evidenced by competitive displacement of methyl orange. Feasible structural models of the PF127:CD polypseudorotaxanes at both the air-water interface and in the bulk solution are proposed.
The sphere-to-rod growth behavior of the triblock copolymer EO(20)PO(70)EO(20) (P123) micelles has been studied in an aqueous medium by dynamic light scattering (DLS), viscometry, and small angle neutron scattering (SANS) techniques. Unlike the other aqueous pluronic systems, the P123 solutions show a time dependent sphere-to-rod micellar growth in the aqueous medium on approaching their cloud points. The rate of micellar growth increases with increase in temperature, but quite interestingly, it improves rather dramatically when the copolymer solutions are subjected to heat cycling, i.e., heating them to the phase separation and subsequently cooling them back to below their cloud points. The observed kinetically restricted micellar growth has been attributed to the slow dynamics of the micellar restructuring processes essential to arrive at the temperature dependent equilibrium structure. It has been suggested that the improvement in the micellar growth rate upon heat cycling is due to overcoming of the activation energy associated with the micellar restructuring process. In the presence of water-structure-making salts like NaCl, such heat cycling produces kinetically stable wormlike micelles at room temperature, which is observed for the first time in the aqueous pluronic systems.
Recently, supramolecular chemistry has been expanding to supramolecular polymer chemistry. The combination of cyclic molecules and linear polymers has provided many kinds of intriguing supramolecular architectures, such as rotaxanes and catenanes. This tutorial review overviews construction of some supramolecular architectures formed by cyclodextrins or their derivatives with guest molecules. In the first part, the construction of supramolecular structures of cyclodextrins with some polymers (polyrotaxanes) is described. In the second part, formation of supramolecular oligomers and polymers formed by cyclodextrin derivatives is described.
The formation of inclusion complexes (ICs) composed of cyclodextrins (CDs) and poly(ethylene oxides)-poly(propylene oxides)-poly(ethylene oxides) (PEO-PPO-PEO) was studied. To this purpose, native and hydroxypropyl cyclodextrins with different cavity size were chosen. The PEO-PPO-PEO copolymers were selected to study the role of the molecular weight, keeping constant the hydrophilic/hydrophobic ratio, and the hydrophilicity. The volumetric studies at 25 degrees C allowed to determine the equilibrium constant and the volume change for the IC formation in water as well as the IC stoichiometry. Surface tension experiments evidenced that the copolymer and the CD interfacial behavior is controlled by the formation of ICs taking place in the bulk phase. It was proved that the differential scanning calorimetry (DSC) is a valid method to describe quantitatively the IC in the solid state. The combination of volumes, DSC and FTIR techniques together with the geometric information highlighted the following points: (1) the included copolymer is in the amorphous state; (2) the IC composed of native CDs adopts a channel structure with two EO units incorporated into one CD molecule; (3) the IC composed of hydroxypropyl-cyclodextrin is a polymeric structure like a necklace decorated with CD rings. Finally, TGA experiments showed that the thermal stability of the IC depends on the nature of both components.
Aqueous solutions of alpha-cyclodextrin (alpha-CD) complex spontaneously with poly(ethylene oxide) (PEO), forming a supramolecular structure known as pseudopolyrotaxane. We have studied the formation of the complex obtained from the threading of alpha-CD onto PEO, both free in solution and adsorbed on colloidal silica. The kinetics of the reaction were studied by gravimetric methods and determined as a function of temperature and solvent composition for the PEO free in solution. PEO was then adsorbed on the surface of colloidal silica particles, and the monomers were displaced by systematically varying the degree of complexation, the concentration of particles, and the molecular weight of the polymer. The effect of the size of the silica particles on the yield of the reaction was also studied. With the adsorbed PEO, the complexation was found to be partial and to take place from the tails of the polymer. The formation of a gel network containing silica at high degrees of complexation was observed. Small-angle X-ray and neutron scattering experiments were performed to study the configuration of the polymeric chains and confirmed the partial desorption of the polymer from the surface of the silica upon complexation.
Small-angle neutron scattering has been used to investigate the associative structures formed by triblock copolymers of poly(ethylene oxide) (PEO)-polypropylene oxide (PPO)-poly(ethylene oxide) (PEO) (also known as Pluronics) and to monitor the structural changes occurring upon complexation with heptakis(2,6-di-O-methyl)-beta-cyclodextrin (hbeta-CD) over the temperature range from 5 to 70 degrees C. At low temperature, the Pluronics are dispersed as unimers. Close to ambient temperature, the hydrophobicity of PPO causes the aggregation of the polymers into spherical micelles with core sizes between 40 and 50 A and a high inclusion of solvent. The aggregation number increases with temperature as the hydrophobicity of the core is gradually enhanced. hbeta-CD spontaneously forms pseudopolyrotaxanes with the triblock copolymers either when in their unimer form or micellized. The complexation results in an increase in the effective critical micellar concentration. It is suggested that the cyclodextrins thread onto the polymer backbone to localize preferentially on the central PPO block, therefore improving its water solubility. At temperatures where the polymers exist in micellar form, complexation with hbeta-CD gives rise to a complete disruption of the aggregates. These processes are highly temperature-dependent. Above 50 degrees C, the break-up of the aggregates is inhibited, and large-scale aggregation is observed.
We present results on the effects of various hydrophobic drugs and additives on the micellar structure of Pluronic F127 solutions. Small-angle neutron scattering experiments on 5wt% F127 solutions were used to measure micelle core size (R(1)), micelle corona size (R(2)), intermicellar interaction distance (R(int)), polydispersity (sigma), and aggregation number (N(agg)); dynamic light scattering was used to measure critical micelle concentration (CMC); and ultraviolet spectroscopy was used to measure drug solubility and apparent micelle-water partition coefficient (K(mw)). The core and corona size were found to generally increase in the presence of the drugs, as did R(int). Both sigma and N(agg) were found to decrease in the presence of most of the drugs, and the CMC was found to vary considerably with no clear correlation. A design of experiments (DOE) approach was used to analyze the results and build empirical correlations. All of the parameters from the SANS experiments were found to depend strongly on drug solubility, with a weak dependence on K(mw) in most cases. The aggregation number, however, was found to depend strongly on both K(mw) and solubility. The correlations can be used to roughly predict the structural parameters of F127 micelles for other hydrophobic drugs.
The supramolecular structures formed between cyclodextrins (CDs) and polymers have inspired interesting developments of novel supramolecular biomaterials. This review will update the recent progress in studies on supramolecular structures based on CDs and block copolymers, followed by the design and synthesis of CD-based supramolecular hydrogels and biodegradable polyrotaxanes for potential controlled drug delivery, and CD-containing cationic polymers and cationic polyrotaxanes for gene delivery. Supramolecular hydrogels based on the self-assembly of the inclusion complexes between CDs with biodegradable block copolymers could be used as promising injectable drug delivery systems for sustained controlled release of macromolecular drugs. Biodegradable polyrotaxanes with drug-conjugated CDs threaded on a polymer chain with degradable end-caps could be interesting supramolecular prodrugs for controlled and targeting delivery of drugs. CD-containing cationic polymers as gene carriers showed reduced cytotoxicity than non-CD-containing polymer counterparts. More importantly, the polyplexes of CD-containing cationic polymers with DNA could be pegylated through a supramolecular process using inclusion complexation between the CD moieties and a modified PEO. Finally, new cationic polyrotaxanes composed of multiple oligoethylenimine-grafted CDs threaded and end-capped on a block copolymer chain were designed and synthesized as a new class of polymeric gene delivery vectors, where the chain-interlocked cationic cyclic units formed an integrated supramolecular entity to function as a macromolecular gene vector. The development of the supramolecular biomaterials through inclusion complexation has opened up a new approach for designing novel drug and gene delivery systems, which may have many advantages over the systems based on the conventional polymeric materials.