Can small air bubbles probe very low frother concentration faster?

The existing literature on the rise velocities of air bubbles in aqueous surfactant solutions adsorbing at the water-air interface focuses mainly on large bubbles (D > 1.2 mm). In addition, due to the way the bubbles in rising bubble experiments are formed, their size is dependent on interfacial tension (the lower the interfacial tension the smaller the bubble). In this paper, smaller air bubbles (D < 505 ± 3 µm) are used to investigate the effect of the bubble size on the detection of two flotation frothers of different adsorption kinetics via bubble rise velocity measurements. We use an alternative method for bubble generation, allowing us to compare the rise velocity of bubbles of the same size in solutions of frothers of varying bulk concentration. The approach taken (ensuring consistent bubble size) ascertains that the buoyancy force component is kept constant when comparing the different solutions. As a consequence, any variations in the bubble rise velocity can be related to changes in the hydrodynamic drag force acting on a rising bubble. The interfacial behavior of frothers, i.e. the adsorption kinetics, interfacial activity and the maximum amount of molecules adsorbed at the interface, are determined from interfacial tension measurements and adsorption isotherms. The differences in the degree of tangential immobilisation caused by two different frothers are discussed in the context of differences in the structure of the dynamic adsorption layer, which is formed during the bubble rise.

Incorporation of FGF-2 into Pharmaceutical Grade Fucoidan/Chitosan Polyelectrolyte Multilayers.

Biopolymer polyelectrolyte multilayers are a commonly studied soft matter system for wound healing applications due to the biocompatibility and beneficial properties of naturally occurring polyelectrolytes. In this work, a popular biopolymer, chitosan, was combined with the lesser known polysaccharide, fucoidan, to create a multilayer film capable of sequestering growth factor for later release. Fucoidan has been shown to act as a heparin-mimic due to similarities in the structure of the two molecules, however, the binding of fibroblast growth factor-2 to fucoidan has not been demonstrated in a multilayer system. This study assesses the ability of fucoidan to bind fibroblast growth factor-2 within a fucoidan/chitosan polyelectrolyte multilayer structure using attenuated total internal reflectance infrared spectroscopy and quartz crystal microbalance with dissipation monitoring. The fibroblast growth factor-2 was sequestered into the polyelectrolyte multilayer as a cationic layer in the uppermost layers of the film structure. In addition, the diffusion of fibroblast growth factor-2 into the multilayer has been assessed.

Adsorption of Carboxymethyl Cellulose onto Titania Particle Films Studied with in Situ IR Spectroscopic Analysis.

Adsorption of carboxymethyl cellulose (CMC) in aqueous solution onto a titania nanoparticle film has been studied using in situ attenuated total reflectance infrared spectroscopy (ATR-IR). CMC was adsorbed onto the positively charged titania surface in neutral, partially charged, and fully charged state. The response of the adsorbed polyelectrolyte layer was monitored upon changing the electrolyte pH and ionic strength. The degree of dissociation of the CMC increased upon adsorption onto the titania surface and changed with the surface coverage. Ionic strength change was observed to influence the degree of dissociation of the adsorbed CMC similar as when in solution. No significant peak shifts were observed in the spectrum of the adsorbed CMC during adsorption or in response to changing solution conditions; therefore, inner-sphere complexation between the carboxyl groups and the titania could not be confirmed. The effect of ion identity on the adsorption process was studied using soft and hard cations and mono- and divalent cations. The presence of a divalent counterion was observed to cause changes in the carboxymethyl vibrations, which can be related to formation of intra- or interchain linkages.

Adsorption of a Polyethoxylated Surfactant from Aqueous Solution to Silica Nanoparticle Films Studied with In Situ Attenuated Total Reflection Infrared Spectroscopy and Colloid Probe Atomic Force Microscopy.

Polyethoxylated (PEO) surfactant adsorption to silica under aqueous conditions is an important physical process in a multitude of industries. Consequently, a considerable number of spectroscopic and other studies have been carried out to ascertain the molecular/structural details of the adsorbed surfactant and the kinetics of PEO surfactant adsorption. However, the use of infrared spectroscopy to probe surfactant adsorption at the silica/aqueous solution interface has been limited because of the instability of silica particle films under aqueous conditions and the opacity of silicon prisms below 1300 cm-1 typically employed for these studies. The work presented here provides infrared spectroscopic measurements of silica particle films formed from differing suspension pH on a diamond internal reflection prism to probe silica particle film stability as a function of pH. The films formed from a suspension pH of 2.5 were found to be the most stable owing to a sol-gel transition of the colloidal suspension upon drying and the reduction in electrostatic repulsion between silica nanoparticles, creating a tightly packed nanoparticle film. Colloid probe atomic force microscopy (CP-AFM) was used to confirm the alteration of surface forces between silica nanoparticles as a function of pH. Particle films from silica suspensions of pH 2.5 were formed in situ on an attenuated total reflection infrared diamond prism and used to probe Triton X-100 adsorption from an aqueous solution. The obtained infrared spectra revealed a critical surface aggregation concentration at a solution concentration of 0.14 mmol L-1, Triton X-100 forms discrete micelles at the silica surface, and the PEO head group preferentially adopts a helical conformation. Most intriguingly, a breakup of the silica particle film was observed at the critical micelle concentration of the surfactant. This is due to the repulsive steric forces arising from the interactions between the PEO corona of the surfactant micelles formed at the silica surface, as confirmed by the CP-AFM measurements.

The influence of polyanion molecular weight on polyelectrolyte multilayers at surfaces: protein adsorption and protein-polysaccharide complexation/stripping on natural polysaccharide films on solid supports.

Two different fucoidan polymers (unfractionated Fucus vesiculosus fucoidan, and fractionated low molecular weight Fucus vesiculosus fucoidan) have been used to create substrates for protein adsorption studies. Polyelectrolyte multilayers were formed using the fucoidans (polyanions) with chitosan as the corresponding polycation. Multilayer formation was studied using zeta potential measurements, quartz crystal microbalance with dissipation monitoring (QCM-D) and attenuated total reflectance (ATR) FTIR spectroscopy. The formation studies reveal that the low molecular weight (LMW) fucoidan produces a less hydrated multilayer, with a significantly increased adsorbed mass, and with fucoidan as the diffusing species during formation. Protein adsorption studies using bovine serum albumin (BSA) were undertaken for solution conditions designed to mimic biological conditions, and to minimise the role of electrical double layer forces in influencing adsorption. Under these conditions, and as revealed by ATR FTIR spectroscopy, BSA is seen to adsorb less substantially to multilayers formed with the LMW fucoidan, and to cause extraction/stripping of the LMW fucoidan from the multilayer. FTIR spectra reveal that the protein adopts a different conformation when adsorbed to the LMW fucoidan multilayer, both relative to the protein in solution and when adsorbed at the surface of the multilayer formed from unfractionated fucoidan.

The influence of polyanion molecular weight on polyelectrolyte multilayers at surfaces: elasticity and susceptibility to saloplasticity of strongly dissociated synthetic polymers at fluid-fluid interfaces.

We studied the interfacial mechanical properties of polyelectrolyte multilayer assemblies of poly(diallylamine hydrochloride) (PAH) and poly(4-styrenesulfonate)sodium salt (PSS) at the air-water interface using axisymmetric drop shape analysis (ADSA) during hydrostatic inflation as a function of aqueous salt concentration and two different polyanion molecular weights (Mw ∼ 13 and 70 kDa). Surface elastic moduli (Gs) ranged from 50 to 300 mN m-1. Using the measured film thickness, the bulk moduli (G) ranged from 10 to 90 MPa consistent with elastomeric solids. This solid-like interface was evidenced by a systematic departure of the inflated shape from the Young-Laplace equation, which assumes a liquid-like interface. Surface elastic moduli increased and bulk elastic moduli decreased with increasing nanomembrane transverse dimension, and multilayers with the lower molecular weight anion were more transversely compact than those of higher molecular weight and displayed a larger elastic modulus. The bulk moduli of both types of multilayer assemblies asymptotically approach a constant value for films with more than two bilayers of polyelectrolyte, consistent with the observed transition from a 'glassy' to 'rubbery' state. Both types of multilayer assemblies displayed plasticization with increasing sodium chloride concentration in the adjoining aqueous phase, i.e. saloplasticity, and exhibited a transition from elastic to plastic response to deformation. The restored mobility of the polyelectrolyte resulting from the shift from intrinsic to extrinsic charge complexation, restores fluidity to the interface and is evidenced by experimental observation of a liquid-like interface when loaded. The higher molecular weight polyanion multilayers plasticized at lower salt concentrations suggesting that the lower melting point of the higher molecular weight polyanion assembly is attributable to a lesser extent of electrostatic cross-linking underscoring the unconventional dependence of molecular weight on saloplasticity in strongly dissociated polyelectrolytes.

In Situ ATR FTIR Spectroscopic Study of the Formation and Hydration of a Fucoidan/Chitosan Polyelectrolyte Multilayer.

The formation of fucoidan/chitosan-based polyelectrolyte multilayers (PEMs) has been studied with in situ Fourier transform infrared (FTIR) spectroscopy. Attenuated total reflectance (ATR) FTIR spectroscopy has been used to follow the sequential build-up of the multilayer, with peaks characteristic of each polymer being seen to increase in intensity with each respective adsorption stage. In addition, spectral processing has allowed for the extraction of spectra from individual adsorbed layers, which have been used to provide unambiguous determination of the adsorbed mass of the PEM at each stage of formation. The PEM was seen to undergo a transition in growth regimes during build-up: from supra-linear to linear. In addition, the wettability of the PEM has been probed at each stage of the build-up, using the captive bubble contact angle technique. The contact angles were uniformly low, but showed variation in value depending on the nature of the outer polymer layer, and this variation correlated with the overall percentage hydration of the PEM (determined from FTIR and quartz crystal microbalance data). The nature of the hydration water within the polyelectrolyte multilayer has also been studied with FTIR spectroscopy, specifically in situ synchrotron ATR FTIR microscopy of the multilayer confined between two solid surfaces. The acquired spectra have enabled the hydrogen bonding environment of the PEM hydration water to be determined. The PEM hydration water is seen to have an environment in which it is subject to fewer hydrogen bonding interactions than in bulk electrolyte solution.

Bubble-surface interactions with graphite in the presence of adsorbed carboxymethylcellulose.

The adsorption of carboxymethylcellulose (CMC), and the subsequent effect on bubble-surface interactions, has been studied for a graphite surface. CMC adsorbs on highly oriented pyrolytic graphite (HOPG) in specific patterns: when adsorbed from a solution of low concentration it forms stretched, isolated and sparsely distributed chains, while upon adsorption from a solution of higher concentration, it forms an interconnected network of multilayer features. The amount and topography of the adsorbed CMC affect the electrical properties as well as the wettability of the polymer-modified HOPG surface. Adsorption of CMC onto the HOPG surface causes the zeta potential to be more negative and the modified surface becomes more hydrophilic. This increase in both the absolute value of zeta potential and the surface hydrophilicity originates from the carboxymethyl groups of the CMC polymer. The effect of the adsorbed polymer layer on wetting film drainage and bubble-surface/particle attachment was determined using high speed video microscopy to monitor single bubble-surface collision, and single bubble Hallimond tube flotation experiments. The time of wetting film drainage and the time of three-phase contact line spreading gets significantly longer for polymer-modified HOPG surfaces, indicating that the film rupture and three-phase contact line expansion were inhibited by the presence of polymer. The effect of longer drainage times and slower dewetting correlated with reduced flotation recovery. The molecular kinetic (MK) model was used to quantify the effect of the polymer on dewetting dynamics, and showed an increase in the jump frequency for the polymer adsorbed at the higher concentration.

Tuning polyelectrolyte multilayer structure by exploiting natural variation in fucoidan chemistry.

Fucoidan is a sulfated polysaccharide that is extracted primarily from seaweed. The polymer contains a natural variation in chemistry based upon the species of seaweed from which it is extracted. We have used two different fucoidans from two different seaweed species (Fucus vesiculosus - FV; and Undaria pinnatifida - UP) as polyanions for the formation of polysaccharide-based polyelectrolyte multilayers (PEMs), to determine if the chemistry of different fucoidans can be chosen to fine-tune the structure of the polymer film. Partially acetylated chitosan was chosen as the polycation for the work, and the presented data illustrate the effect of secondary hydrogen bonding interactions on PEM build-up and properties. Ellipsometry and quartz crystal microbalance with dissipation monitoring (QCM-D) measurements performed during film build-up enabled detailed measurements of layer thickness, adsorbed mass, and the dynamics of the multilayer formation process. High quality atomic force microscopy (AFM) images revealed the differences in morphology of the PEMs formed from the two fucoidans, and allowed for a more direct layer thickness measurement. X-ray photoelectron spectroscopy (XPS) confirmed the chemistry of the films, and an indication of the altered interactions between chitosan and fucoidan with variation in fucoidan type, but also with layer number. Distinct differences were observed between multilayers formed with the two fucoidans, with those constructed using UP having thinner, denser, less hydrated layers than those constructed using FV. These differences are discussed in the context of their varied chemistry, primarily their difference in molecular weight and degree of acetylation.

Spectroscopic study of ionic liquid adsorption from solution onto gold.

Gold was exposed to ethanol solutions containing 0.1 wt% 1-hexyl-3-methyl-imidazolium bis(trifluoromethanesulfonyl)imide (HMIM NTf2), an ionic liquid (IL). The resulting adsorbed layers were interrogated using X-ray photoelectron spectroscopy (XPS - both conventional and synchrotron-based) and spectroscopic ellipsometry. Ellipsometry indicated that the adsorbed layer thickness was smaller than the size of an IL ion pair, with an average determined layer thickness of 0.15 nm. This value indicates that the adsorbed layer on gold is most likely patchy. Conventional XPS revealed that the IL adsorbs irreversibly to gold, with equal amounts of anion and cation in the adsorbed layer. High signal-to-noise synchrotron XPS spectra permitted detailed deconvolution of the S 2p and N 1s peaks for the IL-treated gold, providing more information on adsorbed layer composition and structure. Spectra acquired as a function of X-ray exposure time indicate that non-interacting physisorbed IL components are preferentially removed at the expense of surface bound components, and that anion and cation are both present in the surface bound layer, and also in the layer above. A model structure for the IL adsorbed on gold is proposed.

Carboxymethylcellulose adsorption on molybdenite: the effect of electrolyte composition on adsorption, bubble-surface collisions, and flotation.

The adsorption of carboxymethylcellulose polymers on molybdenite was studied using spectroscopic ellipsometry and atomic force microscopy imaging with two polymers of differing degrees of carboxyl group substitution and at three different electrolyte conditions: 1 × 10(-2) M KCl, 2.76 × 10(-2) M KCl, and simulated flotation process water of multicomponent electrolyte content, with an ionic strength close to 2.76 × 10(-2) M. A higher degree of carboxyl substitution in the adsorbing polymer resulted in adsorbed layers that were thinner and with more patchy coverage; increasing the ionic strength of the electrolyte resulted in increased polymer layer thickness and coverage. The use of simulated process water resulted in the largest layer thickness and coverage for both polymers. The effect of the adsorbed polymer layer on bubble-particle attachment was studied with single bubble-surface collision experiments recorded with high-speed video capture and image processing and also with single mineral molybdenite flotation tests. The carboxymethylcellulose polymer with a lower degree of substitution resulted in almost complete prevention of wetting film rupture at the molybdenite surface under all electrolyte conditions. The polymer with a higher degree of substitution prevented rupture only when adsorbed from simulated process water. Molecular kinetic theory was used to quantify the effect of the polymer on the dewetting dynamics for collisions that resulted in wetting film rupture. Flotation experiments confirmed that adsorbed polymer layer properties, through their effect on the dynamics of bubble-particle attachment, are critical to predicting the effectiveness of polymers used to prevent mineral recovery in flotation.

Oligoelectrolyte-mediated, pH-triggered release of hydrophobic drugs from non-responsive micelles: Influence of oligo(2-vinyl pyridine)-loading on drug-loading, release and cytotoxicity.

pH-responsive polymeric micelles have been extensively studied for nanomedicine and take advantage of pH differentials in tissues for the delivery of large doses of cytotoxic drugs at specific target sites. Despite significant advances in this area, there is a lack of versatile and adaptable strategies to render micelles pH-responsive that could be widely applied to different payloads and applications. To address this deficiency, we introduce the concept of oligoelectrolyte-mediated, pH-triggered release of hydrophobic drugs from non-responsive polymeric micelles as a highly effective approach with broad scope. Herein, we investigate the influence of the oligoelectrolyte, oligo(2-vinyl pyridine) (OVP), loading and polymer molecular weight on the pH-sensitivity, drug loading/release and cytotoxicity of poly(ethylene glycol-b-ε-caprolactone) (PEG-b-PCL) micelles using copolymers with either short or long hydrophobic blocks (PEG4PCL4 and PEG10PCL10, respectively). The micelles were characterized as a function of pH (7.4 to 3.5). Dynamic light scattering (DLS) revealed narrow particle size distributions (PSDs) for both the blank and OVP-loaded micelles at pH 7.4. While OVP encapsulation resulted in an increase in the hydrodynamic diameter (Dh) (cf. blank micelles), a decrease in the pH below 6.5 led to a decrease in the Dh consistent with the ionization and release of OVP and core collapse, which were further supported by proton nuclear magnetic resonance (1H NMR) spectroscopy and UV-visible (UV-vis) spectrophotometry. The change in zeta potential (ζ) with pH for the OVP-loaded PEG4PCL4 and PEG10PCL10 micelles was different, suggesting that the location/distribution of OVP in the micelles is influenced by the polymer molecular weight. In general, co-encapsulation of drugs (doxorubicin (DOX), gossypol (GP), paclitaxel (PX) or 7-ethyl-10-hydroxycamptothecin (SN38)) and OVP in the micelles proceeded efficiently with high encapsulation efficiency percentages (EE%). In vitro release studies revealed the rapid, pH-triggered release of drugs from OVP-loaded PEG10PCL10 micelles within hours, with higher OVP loadings providing faster and more complete release. In comparison, no triggered release was observed for the OVP-loaded PEG4PCL4 micelles, implying a strong molecular weight dependency. In metabolic assays the drug- and OVP-loaded PEG10PCL10 micelles were found to result in significant enhancement of the cytotoxicity compared to drug-loaded micelles (no OVP) or other controls. Importantly, micelles with low OVP loadings were found to be nearly as effective as those with high OVP loadings. These results provide key insights into the tunability of the oligoelectrolyte-mediated approach for the effective formulation of pH-responsive micelles and pH-triggered drug release.

Recent advances in studying crystallisation of mono- and di-glycerides at oil-water interfaces.

This review focuses on the current understanding regarding lipid crystallisation at oil-water interfaces. The main aspects of crystallisation in bulk lipids will be introduced, allowing for a more comprehensive overview of the crystallisation processes within emulsions. Additionally, the properties of an emulsion and the impact of lipid crystallisation on emulsion stability will be discussed. The effect of different emulsifiers on lipid crystallisation at oil-water interfaces will also be reviewed, however, this will be limited to their impact on the interfacial crystallisation of monoglycerides and diglycerides. The final part of the review highlights the recent methodologies used to study crystallisation at oil-water interfaces.

Increasing surface hydrophilicity with biopolymers: a combined single bubble collision, QCM-D and AFM study.

HYPOTHESIS: Naturally extracted polysaccharides, such as guar gum, are promising candidates for environmentally friendly flotation reagents. It is hypothesized that the kinetics of collision of sub- to millimeter gas bubbles with a hydrophobic graphite surface, and the stability of thin liquid film formed between the bubble and surface is affected by an adsorbed layer of guar gum. EXPERIMENTS: A combination of gravimetric (quartz crystal microbalance with dissipation) and imaging (atomic force microscopy) techniques was used to investigate the adsorption of guar gum on graphite surface, while high-speed camera imaging allowed for direct observation of the bubble collision process with guar gum-modified graphite surfaces with millisecond resolution. FINDINGS: Atomic force microscope topography images revealed a guar gum concentration-dependent interconnected network of guar gum molecules adsorbed at graphite surface. These adsorbed molecules at low surface coverage, changed the wettability of the graphite surface, resulting in a film drainage time longer by an order of magnitude, while at higher surface coverage successfully prevented bubble attachment to the graphite surface. Most importantly, the adsorbed layer changed the strength of the bubble's bouncing off the graphite surface. This enhanced bubble bouncing can be correlated with the film drainage time and used to predict a successful bubble-particle attachment.

Teaching an Old Dog New Tricks: A Global Approach to Enhancing the Cytotoxicity of Drug-Loaded, Non-responsive Micelles Using Oligoelectrolytes.

Polymeric micelles have been extensively studied as vectors for the delivery of hydrophobic drugs for the treatment of cancers and other diseases. Despite intensive research, few formulations provide significant benefits, and even fewer have been clinically approved. While many traditional non-responsive micelles have excellent safety profiles, they lack the ability to respond to the intracellular environment and release their cargo in a spatiotemporally defined manner to effectively deliver large doses of cytotoxic drugs into the cytosol of cells that overwhelm efflux pumps. As a novel and adaptable strategy, we hypothesized that well-established non-responsive polymeric micelles could be augmented with a pH-trigger via the co-encapsulation of cytocompatible oligoelectrolytes, which would allow rapid cargo release in the endosome, leading to increased cytotoxicity. Herein, we demonstrate how this strategy can be applied to render non-responsive micelles pH-responsive, resulting in abrupt cargo release at specific and tunable pH values compatible with endosomal delivery, which significantly increased their cytotoxicity up to 3-fold in an ovarian adenocarcinoma (SKOV-3) cell line compared to non-responsive micelles. In comparison, the oligoelectrolyte-loaded micelles were significantly less toxic to healthy 3T3 fibroblasts, indicating a selective cargo release in cancer cell lines. Oligoelectrolytes can be co-encapsulated in the micelles along with drugs at high encapsulation efficiency percentages, which are both ejected from the micelle core upon oligoelectrolyte ionization. Mechanistically, the increase in cytotoxicity appears to also result from the accelerated endosomal escape of the cargo caused by disruption of the endosomal membrane by the simultaneous release of the oligoelectrolytes from the micelles. Furthermore, we show how this approach is broadly applicable to non-responsive micelles regardless of their composition and various classes of hydrophobic chemotherapeutics. The preliminary studies presented here reveal the versatility and wide scope of oligoelectrolyte-mediated, pH-triggered drug release as a compelling and powerful strategy to enhance the cytotoxicity of non-responsive polymeric micelles.

Influence of n-octanol and α-terpineol on thin film stability and bubble attachment to hydrophobic surface.

We have investigated the influence of concentration of surfactants typically used as flotation frothers (α-terpineol and n-octanol) and roughness of the solid surface on phenomena occurring during rising bubble collisions with a model hydrophobic Teflon surface. The time of three-phase contact (TPC) formation (t(TPC)) and the time of drainage (t(D)) of the film formed between the colliding bubble and Teflon surfaces were determined using a high-speed camera working with a frequency 1040 Hz. The Teflon surface roughness was varied on a microscopic scale, within a roughness ranging between 1 and 100 µm. We have found that the roughness of the Teflon surface is a crucial factor of the kinetics of the TPC formation, both in the absence and in the presence of the surfactants. With the surface roughness increasing from ca. 1 to 80 µm the t(TPC) can be shortened by an order of magnitude, i.e. from 105 ms down to a few milliseconds. We have demonstrated that bouncing of the colliding bubble is responsible for the large differences in the times of TPC formation at the Teflon surfaces of different roughness. Low concentrations of α-terpineol and n-octanol caused a decrease in the t(TPC) with respect to distilled water. However, at high concentrations the t(TPC) was prolonged. The prolongation of the time of the TPC formation was dependent on the Teflon surface roughness and we have attributed this effect to different amounts of air present in the cavities and scratches of hydrophobic surfaces of different roughness. The mechanism of prolongation of the t(TPC) at high concentration of surface-active substances (frother overdosage) is proposed.

Influence of Lyophilization and Cryoprotection on the Stability and Morphology of Drug-Loaded Poly(ethylene glycol-b-ε-caprolactone) Micelles.

Polymeric micelles are promising carriers for the delivery of poorly water-soluble drugs, providing enhanced drug solubility, blood circulation times, and bioavailability. Nevertheless, the storage and long-term stability of micelles in solution present challenges requiring the lyophilization and storage of formulations in the solid state, with reconstitution immediately prior to application. Therefore, it is important to understand the effects of lyophilization/reconstitution on micelles, particularly their drug-loaded counterparts. Herein, we investigated the use of ß-cyclodextrin (ß-CD) as a cryoprotectant for the lyophilization/reconstitution of a library of poly(ethylene glycol-b-ε-caprolactone) (PEG-b-PCL) copolymer micelles and their drug-loaded counterparts, as well as the effect of the physiochemical properties of different drugs (phloretin and gossypol). The critical aggregation concentration (CAC) of the copolymers decreased with increasing weight fraction of the PCL block (fPCL), plateauing at ~1 mg/L when the fPCL was >0.45. The blank (empty) and drug-loaded micelles were lyophilized/reconstituted in the absence and presence of ß-CD (9% w/w) and analyzed via dynamic light scattering (DLS) and synchrotron small-angle X-ray scattering (SAXS) to assess for changes in aggregate size (hydrodynamic diameter, Dh) and morphology, respectively. Regardless of the PEG-b-PCL copolymer or the use of ß-CD, the blank micelles displayed poor redispersibility (<10% relative to the initial concentration), while the fraction that redispersed displayed similar Dh to the as-prepared micelles, increasing in Dh as the fPCL of the PEG-b-PCL copolymer increased. While most blank micelles displayed discrete morphologies, the addition of ß-CD or lyophilization/reconstitution generally resulted in the formation of poorly defined aggregates. Similar results were also obtained for drug-loaded micelles, with the exception of several that retained their primary morphology following lyophilization/reconstitution, although no obvious trends were noted between the microstructure of the copolymers or the physicochemical properties of the drugs and their successful redispersion.

Isolating the interface of an emulsion using X-ray scattering and tensiometry to understand protein-modulated alkylglyceride crystallisation.

HYPOTHESIS: Dairy proteins and mono- and diglycerides (MDG) are often used in unison to tailor the properties of dairy-based emulsions. However, there are significant gaps in our understanding of how proteins affect lipid crystallisation at the oil-water interface. We have used a unique combination of interfacially-sensitive techniques to elucidate the impact of dairy proteins on interfacial MDG crystal formation. EXPERIMENTS: The formation temperature of interfacial MDG crystals was assessed through interfacial tension studies via drop shape analysis. Small and Wide-Angle X-ray Scattering measurements were performed on isolated oil-water interfaces, allowing for in-situ interrogation of MDG crystal structure and concentration at and near the interface. FINDINGS: Dairy proteins are seen to reduce the temperature at which MDG crystals form at the oil-water interface. The displacement of proteins upon interfacial crystal formation was also clearly observed in interfacial tension measurements. For the first time, lipid crystals formed at the oil-water interface have been characterised using X-ray scattering. All scattering studies showed no change to the MDG crystal structures at the oil-water interface in the presence of adsorbed proteins. The results demonstrate that informed selection of emulsifier components is critical to controlling interfacial crystallisation with concomitant impact on emulsion stability.

Injectable Diels-Alder cycloaddition hydrogels with tuneable gelation, stiffness and degradation for the sustained release of T-lymphocytes.

Engineered T-cell therapies have proven highly efficacious for the treatment of haematological cancers, but translation of this success to solid tumours has been limited, in part, due to difficulties in maintaining high doses at specific target sites. Hydrogel delivery systems that provide a sustained release of T-cells at the target site are emerging as a promising strategy. Therefore, in this study we aimed to develop an injectable hydrogel that gels in situ via efficient Diels-Alder cycloaddition (DAC) chemistry and provides a sustained release of T-cells through gradual hydrolysis of the hydrogel matrix. Hydrogels were prepared via the DAC between fulvene and maleimide functionalised poly(ethylene glycol) (PEG) derivatives. By adjusting the concentration and molecular weight of the functionalised PEGs in the hydrogel formulation the in vitro gelation time (Tgel), initial Young's modulus (E) and degradation time (Td) could be tailored from 15-150 min, 5-179 kPa and 7-114 h, respectively. Prior to gelation, the formulations could be readily injected through narrow gauge (26 G) needles with the working time correlating closely with the Tgel. A 5 wt% hydrogel formation with conjugated cyclic RGD motif was found to be optimal for the encapsulation and release of CD3+ T-cells with a near linear release profile and >70% cell viability over the first 4 d and release continuing out to 7 d. With their tuneable Tgel, Td and stiffness, the DAC hydrogels provide the opportunity to control the release period and profile of encapsulated cells.

Interrogating the relationship between the microstructure of amphiphilic poly(ethylene glycol-b-caprolactone) copolymers and their colloidal assemblies using non-interfering techniques.

Understanding the microstructural parameters of amphiphilic copolymers that control the formation and structure of aggregated colloids (e.g., micelles) is essential for the rational design of hierarchically structured systems for applications in nanomedicine, personal care and food formulations. Although many analytical techniques have been employed to study such systems, in this investigation we adopted an integrated approach using non-interfering techniques - diffusion nuclear magnetic resonance (NMR) spectroscopy, dynamic light scattering (DLS) and synchrotron small-angle X-ray scattering (SAXS) - to probe the relationship between the microstructure of poly(ethylene glycol-b-caprolactone) (PEG-b-PCL) copolymers [e.g., block molecular weight (MW) and the mass fraction of PCL (fPCL)] and the structure of their aggregates. Systematic trends in the self-assembly behaviour were determined using a large family of well-defined block copolymers with variable PEG and PCL block lengths (number-average molecular weights (Mn) between 2 and 10 and 0.5-15 kDa, respectively) and narrow dispersity (Ð < 1.12). For all of the copolymers, a clear transition in the aggregate structure was observed when the hydrophobic fPCL was increased at a constant PEG block Mn, although the nature of this transition is also dependent on the PEG block Mn. Copolymers with low Mn PEG blocks (2 kDa) were observed to transition from unimers and loosely associated unimers to metastable aggregates and finally, to cylindrical micelles as the fPCL was increased. In comparison, copolymers with PEG block Mn of between 5 and 10 kDa transitioned from heterogenous metastable aggregates to cylindrical micelles and finally, well-defined ellipsoidal micelles (of decreasing aspect ratios) as the fPCL was increased. In all cases, the diffusion NMR spectroscopy, DLS and synchrotron SAXS results provided complementary information and the grounds for a phase diagram relating copolymer microstructure to aggregation behaviour and structure. Importantly, the absence of commonly depicted spherical micelles has implications for applications where properties may be governed by shape, such as, cellular uptake of nanomedicine formulations.