Stimuli-Responsive Polymers for Engineered Emulsions.

Emulsions are complex. Dispersing two immiscible phases, thus expanding an interface, requires effort to achieve and the resultant dispersion is thermodynamically unstable, driving the system toward coalescence. Furthermore, physical instabilities, including creaming, arise due to presence of dispersed droplets of different densities to a continuous phase. Emulsions allow the formulation of oils, can act as vehicles to solubilize both hydrophilic and lipophilic molecules, and can be tailored to desirable rheological profiles, including "gel-like" behavior and shear thinning. The usefulness of emulsions can be further expanded by imparting stimuli-responsive or "smart" behaviors by inclusion of a stimuli-responsive emulsifier, polymer or surfactant. This enables manipulation like gelation, breaking, or aggregation, by external triggers such as pH, temperature, or salt concentration changes. This platform generates functional materials for pharmaceuticals, cosmetics, oil recovery, and colloid engineering, combining both smart behaviors and intrinsic benefit of emulsions. However, with increased functionality comes greater complexity. This review focuses on the use of stimuli-responsive polymers for the generation of smart emulsions, motivated by the great adaptability of polymers for this application and their efficacy as steric stabilizers. Stimuli-responsive emulsions are described according to the trigger used to provide the reader with an overview of progress in this field.

ILC1 drive intestinal epithelial and matrix remodelling.

Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we develop gut organoid cocultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate that murine and human ILC1 secrete transforming growth factor ß1, driving expansion of CD44v6+ epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial-mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.

Evaluating hyaluronic acid dermal fillers: A critique of current characterization methods.

Soft-tissue augmentation has gained much popularity in recent years. Hyaluronic acid (HA) based dermal fillers; a non-permanent injectable device, can restore volume loss, fill fine lines and wrinkles and add curves and contours. HA based dermal fillers entered the non-surgical treatment market in the late 1990s, however there is a lack of data and literature comparing the range of products and detailing the complexities of these products and how it relates to tissue performance. Measuring the physico-chemical properties of these dermal fillers provide key parameters to predict their performance after injection into the body. This article reviews the currently reported methods and parameters used to characterize dermal fillers. The review of these methods and data from the literature provides a useful guide to clinicians and injectors in selecting the optimal product suitable for the needs of each patient.

Antibiotic-in-Cyclodextrin-in-Liposomes: Formulation Development and Interactions with Model Bacterial Membranes.

Gram-negative bacteria possess numerous defenses against antibiotics, due to the intrinsic permeability barrier of their outer membrane (OM), explaining the recalcitrance of some common and life-threatening infections. We report the formulation of a new drug, PPA148, which shows promising activity against all Gram-negative bacteria included in the ESKAPEE pathogens. PPA148 was solubilized by inclusion complexation with cyclodextrin followed by encapsulation in liposomes. The complex and liposomal formulation presented increased activity against E. coli compared to the pure drug when assessed with the Kirby Bauer assay. The novel formulation containing 1 µg PPA148 reached similar efficacy levels equivalent to those of 30 µg of pure rifampicin. A range of biophysical techniques was used to explore the mechanism of drug uptake. Langmuir trough (LT) and neutron reflectivity (NR) techniques were employed to monitor the interactions between the drug and the formulation with model membranes. We found evidence for liposome fusion with the model Gram-negative outer membrane and for cyclodextrins acting as inner membrane (IM) permeation enhancers without presenting intrinsic antimicrobial activity. An antibiotic-in-cyclodextrin-in-liposomes (ACL) formulation was developed, which targets both the bacterial OM and IM, and offers promise as a means to breach the Gram-negative cell envelope.

Supramolecular Hybrid Structures and Gels from Host-Guest Interactions between α-Cyclodextrin and PEGylated Organosilica Nanoparticles.

Polypseudorotaxanes are polymer chains threaded by molecular rings that are free to unthread; these "pearl-necklace" can self-assemble further, leading to higher-order supramolecular structures with interesting functionalities. In this work, the complexation between α-cyclodextrin (α-CD), a cyclic oligosaccharide of glucopyranose units, and poly(ethylene glycol) (PEG) grafted to silica nanoparticles was studied. The threading of α-CD onto the polymeric chains leads to their aggregation into bundles, followed by either the precipitation of the inclusion complex or the formation of a gel phase, in which silica nanoparticles are incorporated. The kinetics of threading, followed by turbidimetry, revealed a dependence of the rate of complexation on the following parameters: the concentration of α-CD, temperature, PEG length (750, 4000, and 5000 g mol-1), whether the polymer is grafted or free in solution, and the density of grafting. Complexation is slower, and temperature has a higher impact on PEG grafted on silica nanoparticles compared to PEG free in solution. Thermodynamic parameters extracted from the transition-state theory showed that inclusion complex formation is favored with grafted PEG compared to free PEG and establishes a ratio of complexation of five to six ethylene oxide units per cyclodextrin. The complexation yields, determined by gravimetry, revealed that much higher yields are obtained with longer chains and higher grafting density. Thermogravimetric analysis and Fourier transform infrared spectroscopy on the inclusion complex corroborate the number of macrocycles threaded on the chains. A sol-gel transition was observed with the longer PEG chain (5k) at specific mixing ratios; oscillatory shear rheology measurements confirmed a highly solid-like behavior, with an elastic modulus G' of up to 25 kPa, higher than that in the absence of silica. These results thus provide the key parameters dictating inclusion complex formation between cyclodextrin and PEG covalently attached to colloidal silica and demonstrate a facile route toward soft nanoparticle gels based on host-guest interactions.

Influence of the Surfactant Structure on Photoluminescent π-Conjugated Polymer Nanoparticles: Interfacial Properties and Protein Binding.

π-Conjugated polymer nanoparticles (CPNs) are under investigation as photoluminescent agents for diagnostics and bioimaging. To determine whether the choice of surfactant can improve CPN properties and prevent protein adsorption, five nonionic polyethylene glycol alkyl ether surfactants were used to produce CPNs from three representative π-conjugated polymers. The surfactant structure did not influence size or yield, which was dependent on the nature of the conjugated polymer. Hydrophobic interaction chromatography, contact angle, quartz crystal microbalance, and neutron reflectivity studies were used to assess the affinity of the surfactant to the conjugated polymer surface and indicated that all surfactants were displaced by the addition of a model serum protein. In summary, CPN preparation methods which rely on surface coating of a conjugated polymer core with amphiphilic surfactants may produce systems with good yields and colloidal stability in vitro, but may be susceptible to significant surface alterations in physiological fluids.

Structural and Spectroscopic Characterization of TPGS Micelles: Disruptive Role of Cyclodextrins and Kinetic Pathways.

The aggregation and structure of d-α-tocopheryl polyethylene glycol succinate micelles, TPGS-1000, an amphiphilic derivative of vitamin E, were characterized using scattering and spectroscopic methods, and the impact of different cyclodextrins (CDs) on the self-assembly was investigated, with the view of combining these two versatile pharmaceutical excipients in drug formulations. Combined small-angle neutron scattering (SANS), dynamic light scattering, and time-resolved and steady-state fluorescence emission experiments revealed a core-shell architecture with a high aggregation number (Nagg ≈ 100) and a highly hydrated poly(ethylene oxide) corona (∼11 molecules of solvent per ethylene oxide unit). Micelles form gradually, with no sharp onset. Structural parameters and hydration of the aggregates were surprisingly stable with both temperature and concentration, which is a critical advantage for their use in pharmaceutical formulations. CDs were shown to affect the self-assembly of TPGS in different ways. Whereas native CDs induced the precipitation of a solid complex (pseudopolyrotaxane), methylated ß-CDs led to different outcomes: constructive (micellar expansion), destructive (micellar rupture), or no effect, depending on the number of substituents and whether the substitution pattern was regular or random on the rims of the macrocycle. Time-resolved SANS studies on mixtures of TPGS with regularly dimethylated ß-CD (DIMEB), which ruptures the micelles, revealed an almost instantaneous demicellization (<100 ms) and showed that the process involved the formation of large aggregates whose size evolved over time. Micellar rupture is caused by the formation of a TPGS-DIMEB inclusion complex, involving the incorporation of up to three macrocycles on the tocopherol, as shown by proton nuclear magnetic resonance (NMR) and ROESY NMR. Analysis of NMR data using Hill's equation revealed that the binding is rather cooperative, with the threading of the CD favoring the subsequent inclusion of additional CDs on the aliphatic moiety.

Structure and Rheology of Poloxamine T1107 and Its Nanocomposite Hydrogels with Cyclodextrin-Modified Barium Titanate Nanoparticles.

We report the preparation of a nanocomposite hydrogel based on a poloxamine gel matrix (Tetronic T1107) and cyclodextrin (CD)-modified barium titanate (BT) nanoparticles. The micellization and sol-gel behavior of pH-responsive block copolymer T1107 were fully characterized by small-angle neutron scattering (SANS), dynamic light scattering (DLS), and Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy as a function of concentration, pH and temperature. SANS results reveal that spherical micelles in the low concentration regime present a dehydrated core and highly hydrated shell, with a small aggregation number and size, highly dependent on the degree of protonation of the central amine spacer. At high concentration, T1107 undergoes a sol-gel transition, which is inhibited at acidic pH. Nanocomposites were prepared by incorporating CD-modified BT of two different sizes (50 and 200 nm) in concentrated polymer solutions. Rheological measurements show a broadening of the gel region, as well as an improvement of the mechanical properties, as assessed by the shear elastic modulus, G' (up to 200% increase). Initial cytocompatibility studies of the nanocomposites show that the materials are nontoxic with viabilities over 70% for NIH3T3 fibroblast cell lines. Overall, the combination of Tetronics and modified BaTiO3 provides easily customizable systems with promising applications as soft piezoelectric materials.

Competitive and Synergistic Interactions between Polymer Micelles, Drugs, and Cyclodextrins: The Importance of Drug Solubilization Locus.

Polymeric micelles, in particular PEO-PPO-based Pluronic, have emerged as promising drug carriers, while cyclodextrins (CD), cyclic oligosaccharides with an apolar cavity, have long been used for their capacity to form inclusion complexes with drugs. Dimethylated ß-cyclodextrin (DIMEB) has the capacity to fully breakup 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 toward higher drug partitioning and lower drug/CD binding compared to 25 °C ( Valero, M.; Dreiss, C. A. Growth, Shrinking, and Breaking of Pluronic Micelles in the Presence of Drugs and/or ß-Cyclodextrin, a Study by Small-Angle Neutron Scattering and Fluorescence Spectroscopy . Langmuir 2010 , 26 , 10561 - 10571 ). The impact of drugs on micellar structure was characterized by small-angle neutron scattering (SANS), while their solubilization 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 breakup in the presence of drugs is substantially slower (100s of seconds) than for the free micelles (<100 ms) ( Valero, M.; Grillo, I.; Dreiss, C. A. Rupture of Pluronic Micelles by Di-Methylated ß-Cyclodextrin Is Not Due to Polypseudorotaxane Formation . J. Phys. Chem. B 2012 , 116 , 1273 - 1281 ). These results combined together give new insights into the mechanisms of protection of the drugs against CD-induced micellar breakup. The outcomes are practical guidelines to improve the design of drug delivery systems as well as a better understanding of competitive assembly mechanisms leading to shape and function modulation.

Modulating the self-assembly of amphiphilic X-shaped block copolymers with cyclodextrins: structure and mechanisms.

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 Tetronic 904 (T904, Mw 6700). 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 breakup, with dimethylated ß-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 (1)H 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 demicellization. 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.

Selective tuning of the self-assembly and gelation of a hydrophilic poloxamine by cyclodextrins.

Complexes formed between cyclodextrins (CDs) and polymers - pseudopolyrotaxanes (PPRs) - are the starting point of a multitude of supramolecular structures, which are proposed for a wide range of biomedical and technological applications. In this work, we investigate 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 micellization and the sol-gel transition. At low concentrations, small-angle neutron scattering (SANS) combined with 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, whereas 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 the 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 with the temperature. Native CDs (α, ß, γ-CD) can complex T1307, resulting in the precipitation of a PPR. Instead, modified CDs compete with micellization to an extent that is critically dependent on the nature of the substitution. (1)H and ROESY NMR combined with SANS demonstrate that dimethylated ß-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 ß-CD, which, while not affecting the CMT, is able to fully suppress the gel phase.

Using inclusion complexes with cyclodextrins to explore the aggregation behavior of a ruthenium metallosurfactant.

The aggregation behavior of a chiral metallosurfactant, bis(2,2'-bipyridine)(4,4'-ditridecyl-2,2'-bipyridine)ruthenium(II) dichloride (Ru2(4)C13), synthesized as a racemic mixture was characterized by small-angle neutron scattering, light scattering, NMR, and electronic spectroscopies. The analysis of the SANS data indicates that micelles are prolate ellipsoids over the range of concentrations studied, with a relatively low aggregation number, and the micellization takes place gradually with increasing concentration. The presence of cyclodextrins (ß-CD and γ-CD) induces the breakup of the micelles and helps to establish that micellization occurs at a very slow exchange rate compared to the NMR time scale. The open structure of this metallosurfactant enables the formation of very stable complexes of 3:1 stoichiometry, in which one CD threads one of the hydrocarbon tails and two CDs the other, in close contact with the polar head. The complex formed with ß-CD, more stable than the one formed with the wider γ-CD, is capable of resolving the Δ and Λ enantiomers at high CD/surfactant molar ratios. The chiral recognition is possible due to the very specific interactions taking place when the ß-CD covers-via its secondary rim-part of the diimine moiety connected to the hydrophobic tails. A SANS model comprising a binary mixture of hard spheres (complex + micelles) was successfully used to study quantitatively the effect of the CDs on the aggregation of the surfactant.

Exploring the kinetics of gelation and final architecture of enzymatically cross-linked chitosan/gelatin gels.

Small-angle neutron scattering (SANS) was used to characterize the nanoscale structure of enzymatically cross-linked chitosan/gelatin hydrogels obtained from two protocols: a pure chemical cross-linking process (C), which uses the natural enzyme microbial transglutaminase, and a physical-co-chemical (PC) hybrid process, where covalent cross-linking is combined with the temperature-triggered gelation of gelatin, occurring through the formation of triple-helices. SANS measurements on the final and evolving networks provide a correlation length (ξ), which reflects the average size of expanding clusters. Their growth in PC gels is restricted by the triple-helices (ξ ∼ 10s of Å), while ξ in pure chemical gels increases with cross-linker concentration (∼100s of Å). In addition, the shear elastic modulus in PC gels is higher than in pure C gels. Our results thus demonstrate that gelatin triple helices provide a template to guide the cross-linking process; overall, this work provides important structural insight to improve the design of biopolymer-based gels.

Remarkable viscoelasticity in mixtures of cyclodextrins and nonionic surfactants.

We report the effect of native cyclodextrins (α, ß, and γ) and selected derivatives in modulating the self-assembly of the nonionic surfactant polyoxyethylene cholesteryl ether (ChEO10) and its mixtures with triethylene glycol monododecyl ether (C12EO3), which form wormlike micelles. Cyclodextrins (CDs) generally induce micellar breakup through a host-guest interaction with surfactants; instead, we show that a constructive effect, leading to gel formation, is obtained with specific CDs and that the widely invoked host-guest interaction may not be the only key to the association. When added to wormlike micelles of ChEO10 and C12EO3, native ß-CD, 2-hydroxyethyl-ß-CD (HEBCD), and a sulfated sodium salt of ß-CD (SULFBCD) induce a substantial increase of the viscoelasticity, while methylated CDs rupture the micelles, leading to a loss of the viscosity, and the other CDs studied (native α- and γ- and hydroxypropylated CDs) show a weak interaction. Most remarkably, the addition of HEBCD or SULFBCD to pure ChEO10 solutions (which are low-viscosity, Newtonian fluids of small, ellipsoidal micelles) induces the formation of transparent gels. The combination of small-angle neutron scattering, dynamic light scattering, and cryo-TEM reveals that both CDs drive the elongation of ChEO10 aggregates into an entangled network of wormlike micelles. (1)H NMR and fluorescence spectroscopy demonstrate the formation of inclusion complexes between ChEO10 and methylated CDs, consistent with the demicellization observed. Instead, HEBCD forms a weak complex with ChEO10, while no complex is detected with SULFBCD. This shows that inclusion complex formation is not the determinant event leading to micellar growth. HEBCD:ChEO10 complex, which coexists with the aggregated surfactant, could act as a cosurfactant with a different headgroup area. For SULFBCD, intermolecular interactions via the external surface of the CD may be more relevant.

Molecular variations in aromatic cosolutes: critical role in the rheology of cationic wormlike micelles.

Wormlike micelles formed by the addition to cetyltrimethylammonium bromide (CTAB) of a range of aromatic cosolutes with small molecular variations in their structure were systematically studied. Phenol and derivatives of benzoate and cinnamate were used, and the resulting mixtures were studied by oscillatory, steady-shear rheology, and the microstructure was probed by small-angle neutron scattering. The lengthening of the micelles and their entanglement result in remarkable viscoelastic properties, making rheology a useful tool to assess the effect of structural variations of the cosolutes on wormlike micelle formation. For a fixed concentration of CTAB and cosolute (200 mmol L(-1)), the relaxation time decreases in the following order: phenol > cinnamate> o-hydroxycinnamate > salicylate > o-methoxycinnamate > benzoate > o-methoxybenzoate. The variations in viscoelastic response are rationalized by using Mulliken population analysis to map out the electronic density of the cosolutes and quantify the barrier to rotation of specific groups on the aromatics. We find that the ability of the group attached to the aromatic ring to rotate is crucial in determining the packing of the cosolute at the micellar interface and thus critically impacts the micellar growth and, in turn, the rheological response. These results enable us for the first time to propose design rules for the self-assembly of the surfactants and cosolutes resulting in the formation of wormlike micelles with the cationic surfactant CTAB.

CO2-switchable multi-compartment micelles with segregated corona.

CO2-switchable multi-compartment micelles (MCMs) with a segregated corona formed by a purpose-designed ABC triblock copolymer are reported. They can be switched "on" and "off" when sequentially treated with CO2 and N2, due to the protonation-deprotonation of the tertiary amine groups along the polymer skeleton.

Smart wormlike micelles.

A major scientific challenge of the past decade pertaining to the field of soft matter has been to craft 'adaptable' materials, inspired by nature, which can dynamically alter their structure and functionality on demand, in response to triggers produced by environmental changes. Amongst these, 'smart' surfactant wormlike micelles, responsive to external stimuli, are a particularly recent area of development, yet highly promising, given the versatility of the materials but simplicity of the design-relying on small amphiphilic molecules and their spontaneous self-assembly. The switching 'on' and 'off' of the micellar assembly structures has been reported using electrical, optical, thermal or pH triggers and is now envisaged for multiple stimuli. The structural changes, in turn, can induce major variations in the macroscopic characteristics, affecting properties such as viscosity and elasticity and sometimes even leading to a spontaneous and effective 'sol-gel' transition. These original smart materials based on wormlike micelles have been successfully used in the oil industry, and offer a significant potential in a wide range of other technological applications, including biomedicine, cleaning processes, drag reduction, template synthesis, to name but a few. This review will report results in this field published over the last few years, describe the potential and practical applications of stimuli-responsive wormlike micelles and point out future challenges.

Dynamic covalent surfactants and their uses in the development of smart materials.

Dynamic covalent chemistry, which leverages the dynamic nature of reversible covalent bonds controlled by the conditions of reaction equilibrium, has demonstrated great potential in diverse applications related to both the stability of covalent bonds and the possibility of exchanging building blocks, imparting to the systems the possibility of "error checking" and "proof-reading". By incorporating dynamic covalent bonds into surfactant molecular architectures, combinatorial libraries of surfactants with bespoke functionalities can be readily fabricated through a facile strategy, with minimum effort in organic synthesis. Consequently, a multidisciplinary field of research involving the creation and application of dynamic covalent surfactants has recently emerged, which has aroused great attention in surfactant and colloid science, supramolecular chemistry, self-assembly, smart materials, drug delivery, and nanotechnology. This review reports results in this field published over recent years, discusses the possibilities presented by dynamic covalent surfactants and their applications in developing smart self-assembled materials, and outlines some future perspectives.

Injectable PEG Hydrogels with Tissue-Like Viscoelasticity Formed through Reversible Alendronate-Calcium Phosphate Crosslinking for Cell-Material Interactions.

Synthetic hydrogels provide controllable 3D environments, which can be used to study fundamental biological phenomena. The growing body of evidence that cell behavior depends upon hydrogel stress relaxation creates a high demand for hydrogels with tissue-like viscoelastic properties. Here, a unique platform of synthetic polyethylene glycol (PEG) hydrogels in which star-shaped PEG molecules are conjugated with alendronate and/or RGD peptides, attaining modifiable degradability as well as flexible cell adhesion, is created. Novel reversible ionic interactions between alendronate and calcium phosphate nanoparticles, leading to versatile viscoelastic properties with varying initial elastic modulus and stress relaxation time, are identified. This new crosslinking mechanism provides shear-thinning properties resulting in differential cellular responses between cancer cells and stem cells. The novel hydrogel system is an improved design to the other ionic crosslink platforms and opens new avenues for the development of pathologically relevant cancer models, as well as minimally invasive approaches for cell delivery for potential regenerative therapies.

Tuning the viscoelasticity of nonionic wormlike micelles with ß-cyclodextrin derivatives: a highly discriminative process.

We report the influence of five ß-cyclodextrin (ß-CD) derivatives, namely: randomly methylated ß-cyclodextrin (MBCD), heptakis (2,6-di-O-methyl)-ß-cyclodextrin (DIMEB), heptakis (2,3,6-tri-O-methyl)-ß-cyclodextrin (TRIMEB), 2-hydroxyethyl-ß-cyclodextrin (HEBCD) and 2-hydroxypropyl-ß-cyclodextrin (HPBCD), on the self-assembly of mixtures of nonionic 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 ß-CDs (MBCD, DIMEB, TRIMEB) induced a substantial disruption of the solid-like viscoelastic behavior, as shown from a loss of the Maxwell behavior, 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 ß-CDs and both surfactants involved in WLM formation. Instead, hydroxyl-ß-CDs had a very different effect on the WLM. HPBCD only slightly reduced the solid-like behavior, without suppressing it. Quite remarkably, the addition of HEBCD reinforced the solid-like characteristics and 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 affected the ChEO10. For both DIMEB and HEBCD, time-resolved SANS measurements showed that morphology changes underlying these macroscopic changes occur in less than 100 ms.