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.

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.

Regulating the structural polymorphism and protein corona composition of phytantriol-based lipid nanoparticles using choline ionic liquids.

Lipid-based lyotropic liquid crystalline nanoparticles (LCNPs) face stability challenges in biological fluids during clinical translation. Ionic Liquids (ILs) have emerged as effective solvent additives for tuning the structure of LCNP's and enhancing their stability. We investigated the effect of a library of 21 choline-based biocompatible ILs with 9 amino acid anions as well as 10 other organic/inorganic anions during the preparation of phytantriol (PHY)-based LCNPs, followed by incubation in human serum and serum proteins. Small angle X-ray scattering (SAXS) results show that the phase behaviour of the LCNPs depends on the IL concentration and anion structure. Incubation with human serum led to a phase transition from the inverse bicontinuous cubic (Q2) to the inverse hexagonal (H2) mesophase, influenced by the specific IL present. Liquid chromatography-mass spectrometry (LC-MS) and proteomics analysis of selected samples, including PHY control and those with choline glutamate, choline hexanoate, and choline geranate, identified abundant proteins in the protein corona, including albumin, apolipoproteins, and serotransferrin. The composition of the protein corona varied among samples, shedding light on the intricate interplay between ILs, internal structure and surface chemistry of LCNPs, and biological fluids.

Evaluating human milk as a drug delivery vehicle for clofazimine to premature infants.

Human milk is proposed as a drug delivery vehicle suitable for use in neonatal patients. Clofazimine, traditionally used for the treatment of leprosy and tuberculosis, is emerging as a treatment for cryptosporidiosis in infants, however its poor aqueous solubility has led to its commercial formulation as a waxy lipid formulation in a capsule, a format that is not suitable for infants. In this study, the evaluation of pasteurised human milk for the delivery of clofazimine was investigated using an in vitro lipolysis model to simulate gastric and intestinal digestion. The total lipid composition of the human milk was characterised alongside the liberated fatty acid species following digestion for comparison to alternative lipid-based delivery systems. Small-angle X-ray scattering was used to measure the presence of crystalline clofazimine during digestion and hence the extent of drug solubilisation. High-performance liquid chromatography was used to quantify the mass of clofazimine solubilised per gram of human milk fat (drug-to-fat ratio) in digested and undigested human milk. The digestion process was essential for the solubilisation of clofazimine, with digested human milk solubilising a sufficient dose of clofazimine for treatment of a premature infant. Human milk solubilised the clofazimine to a greater extent than bovine milk and infant formula during digestion, most likely as a result of differing lipid composition and increased long-chain fatty acid concentrations. These findings show that human milk enhances the solubility of clofazimine as a model drug and may be a suitable drug delivery vehicle for infant populations requiring therapeutic treatment.

Construction of a Synthetic Colostrum Substitute and Its Protection of Intestinal Cells against Inflammation in an In Vitro Model of Necrotizing Enterocolitis.

Colostrum provides bioactive components that are essential for the colonization of microbiota in the infant gut, while preventing infectious diseases such as necrotizing enterocolitis. As colostrum is not always available from the mother, particularly for premature infants, effective and safe substitutes are keenly sought after by neonatologists. The benefits of bioactive factors in colostrum are recognized; however, there have been no accounts of human colostrum being studied during digestion of the lipid components or their self-assembly in gastrointestinal environments. Due to the weaker bile pool in infants than adults, evaluating the lipid composition of human colostrum and linking it to structural self-assembly behavior is important in these settings and thus enabling the formulation of substitutes for colostrum. This study is aimed at the rational design of an appropriate lipid component for a colostrum substitute and determining the ability of this formulation to reduce inflammation in intestinal cells. Gas chromatography was utilized to map lipid composition. The self-assembly of lipid components occurring during digestion of colostrum was monitored using small-angle X-ray scattering for comparison with substitute mixtures containing pure triglyceride lipids based on their abundance in colostrum. The digestion profiles of human colostrum and the substitute mixtures were similar. Subtle differences in lipid self-assembly were evident, with the substitute mixtures exhibiting additional non-lamellar phases, which were not seen for human colostrum. The difference is attributable to the distribution of free fatty acids released during digestion. The biological markers of necrotizing enterocolitis were modulated in cells that were treated with bifidobacteria cultured on colostrum substitute mixtures, compared to those treated with infant formula. These findings provide an insight into a colostrum substitute mixture that resembles human colostrum in terms of composition and structural behavior during digestion and potentially reduces some of the characteristics associated with necrotizing enterocolitis.

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.

Implications of the Digestion of Milk-Based Formulations for the Solubilization of Lopinavir/Ritonavir in a Combination Therapy.

The development of formulation approaches to coadminister lopinavir and ritonavir antiretroviral drugs to children is necessary to ensure optimal treatment of human immunodeficiency virus (HIV) infection. It was previously shown that milk-based lipid formulations show promise as vehicles to deliver antimalarial drugs by enhancing their solubilization during the digestion of the milk lipids under intestinal conditions. In this study, we investigate the role of digestion of milk and infant formula on the solubilization behavior of lopinavir and ritonavir to understand the fate of drugs in the gastrointestinal (GI) tract after oral administration. Small angle X-ray scattering (SAXS) was used to probe the presence of crystalline drugs in suspension during digestion. In particular, the impact of one drug on the solubilization of the other was elucidated to reveal potential drug-drug interactions in a drug combination therapy. Our results showed that lopinavir and ritonavir affected the solubilization of each other during digestion in lipid-based formulations. While addition of ritonavir to lopinavir improved the overall solubilization of lopinavir, the impact of lopinavir was to reduce ritonavir solubilization as digestion progressed. These findings highlight the importance of assessing the solubilization of individual drugs in a combined matrix in order to dictate the state of drugs available for subsequent absorption and metabolism. Enhancement in the solubilization of lopinavir and ritonavir in a drug combination setting in vitro also supported the potential for food effects on drug exposure.

Cholesterol stabilization of phospholipid vesicles against bile-induced solubilization.

Sphingomyelin (SM) and cholesterol complex to form functional liquid-ordered (Lo) domains. It has been suggested that the detergent resistance of these domains plays a key role during gastrointestinal digestion of the milk fat globule membrane (MFGM), which is rich in both SM and cholesterol. Small-angle X-ray scattering was employed to determine the structural alterations that occur when milk sphingomyelin (MSM)/cholesterol, egg sphingomyelin (ESM)/cholesterol, soy phosphatidylcholine (SPC)/cholesterol, and milk fat globule membrane (MFGM) phospholipid/cholesterol model bilayer systems were incubated with bovine bile under physiological conditions. The persistence of diffraction peaks was indicative of multilamellar vesicles of MSM with cholesterol concentrations > 20 % mol, and also for ESM with or without cholesterol. The complexation of ESM with cholesterol is therefore capable of inhibiting the resulting vesicles from disruption by bile at lower cholesterol concentrations than MSM/cholesterol. After subtraction of background scattering by large aggregates in the bile, a Guinier fitting was used to determine changes in the radii of gyration (Rgs) over time for the biliary mixed micelles after mixing the vesicle dispersions with bile. Swelling of the micelles by phospholipid solubilization from vesicles was a function of cholesterol concentration, with less swelling of the micelles occurring as the cholesterol concentration was increased. With 40% mol cholesterol, the Rgs of the bile micelles mixed with MSM/cholesterol, ESM/cholesterol, and MFGM phospholipid/cholesterol were equal to the control (PIPES buffer + bovine bile), indicating negligible swelling of the biliary mixed micelles.

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.

Revisiting the Dissolution of Praziquantel in Biorelevant Media and the Impact of Digestion of Milk on Drug Dissolution.

Praziquantel is a poorly water-soluble drug used to treat parasitic infections. Previous studies have suggested that its rate and extent of dissolution in milk and biorelevant media are slow and limited compared to dissolution in the pharmacopoeial-recommended medium, despite being reported as displaying a positive food effect upon administration. This study aimed to revisit the dissolution of praziquantel in biorelevant media and milk to better understand this apparent dichotomy. The context of digestion was introduced to better understand drug solubilisation under more relevant gastrointestinal conditions. The amount of praziquantel solubilised in the various media during digestion was quantified using high performance liquid chromatography (HPLC) and the kinetics of dissolution were confirmed by tracking the disappearance of solid crystalline drug using in situ small angle X-ray scattering (SAXS). For the dissolution media, where sodium lauryl sulfate (SLS) is typically included as a wetting agent, a prominent effect of SLS on drug dissolution was also apparent where >2.5 fold more drug was solubilised in SLS-containing dissolution medium compared to that without (0.1 M HCl only). In milk, significant dissolution of praziquantel was observed only during digestion and not during dispersion, hence suggesting that (1) milk can be potentially administered with praziquantel to improve oral bioavailability and (2) incorporating a digestion step into existing in vitro dissolution testing can better reflect the potential for a positive food effect when lipids are present.

Microstructure-Thermal Property Relationships of Poly (Ethylene Glycol-b-Caprolactone) Copolymers and Their Micelles.

The crystallinity of polymers strongly affects their properties. For block copolymers, whereby two crystallisable blocks are covalently tethered to one another, the molecular weight of the individual blocks and their relative weight fraction are important structural parameters that control their crystallisation. In the case of block copolymer micelles, these parameters can influence the crystallinity of the core, which has implications for drug encapsulation and release. Therefore, in this study, we aimed to determine how the microstructure of poly(ethylene glycol-b-caprolactone) (PEG-b-PCL) copolymers contributes to the crystallinity of their hydrophobic PCL micelle cores. Using a library of PEG-b-PCL copolymers with PEG number-average molecular weight (Mn) values of 2, 5, and 10 kDa and weight fractions of PCL (fPCL) ranging from 0.11 to 0.67, the thermal behaviour and morphology were studied in blends, bulk, and micelles using differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WXRD), and Synchrotron wide-angle X-ray scattering (WAXS). Compared to PEG and PCL homopolymers, the block copolymers displayed reduced crystallinity in the bulk phase and the individual blocks had a large influence on the crystallisation of one another. The fPCL was determined to be the dominant contributor to the extent and order of crystallisation of the two blocks. When fPCL < 0.35, the initial crystallisation of PEG led to an amorphous PCL phase. At fPCL values between 0.35 and 0.65, PEG crystallisation was followed by PCL crystallisation, whereas this behaviour was reversed when fPCL > 0.65. For lyophilised PEG-b-PCL micelles, the crystallinity of the core increased with increasing fPCL, although the core was predominately amorphous for micelles with fPCL < 0.35. These findings contribute to understanding the relationships between copolymer microstructure and micelle core crystallinity that are important for the design and performance of micellar drug delivery systems, and the broader application of polymer micelles.

Small-volume in vitro lipid digestion measurements for assessing drug dissolution in lipid-based formulations using SAXS.

Lipid-based formulations improve the absorption capacity of poorly-water-soluble drugs and digestion of the formulation is a critical step in that absorption process. A recent approach to understanding the propensity for drug to dissolve in digesting lipid-based formulations couples an in vitro pH-stat lipolysis model to small-angle X-ray scattering (SAXS) by means of a flow-through capillary. However, the conventional pH-stat apparatus used to measure the extent of lipid digestion during such experiments requires digest volumes of 15-30 mL and drug doses of 50-200 mg, which is problematic for scarce compounds and can require excessive amounts of formulation reagents. This manuscript describes an approach to reduce the amount of material required for in vitro lipolysis experiments coupled to SAXS, for use in instances where the amount of drug or formulation medium is limited. Importantly, this was achieved while maintaining the pH stat conditions, which is critical for maintaining biorelevance and driving digestion to completion. The digestibility of infant formula with the poorly-water-soluble drugs halofantrine and clofazimine dispersed into it was measured as an exemplar paediatric-friendly lipid formulation. Halofantrine was incorporated in its powdered free base form and clofazimine was incorporated both as unformulated drug powder and as drug in nanoparticulate form prepared using Flash NanoPrecipitation. The fraction of triglyceride digested was found to be independent of vessel size and the incorporation of drug. The dissolution of the two forms of clofazimine during the digestion of infant formula were then measured using synchrotron SAXS, which revealed complete and partial solubilisation over 30 min of digestion for the powdered drug and nanoparticle formulations, respectively. The main challenge in reducing the volume of the measurements was in ensuring that thorough mixing was occurring in the smaller digestion vessel to provide uniform sampling of the dispersion medium.

Impact of pasteurization on the self-assembly of human milk lipids during digestion.

Human milk is critical for the survival and development of infants. This source of nutrition contains components that protect against infections while stimulating immune maturation. In cases where the mother's own milk is unavailable, pasteurized donor milk is the preferred option. Although pasteurization has been shown to have minimal impact on the lipid and FA composition before digestion, no correlation has been made between the impact of pasteurization on the FFA composition and the self-assembly of lipids during digestion, which could act as delivery mechanisms for poorly water-soluble components. Pooled nonpasteurized and pasteurized human milk from a single donor was used in this study. The evolving FFA composition during digestion was determined using GC coupled to a flame ionization detector. In vitro digestion coupled to small-angle X-ray scattering was utilized to investigate the influence of different calcium levels, fat content, and the presence of bile salts on the extent of digestion and structural behavior of human milk lipids. Almost complete digestion was achieved when bile salts were added to the systems containing high calcium to milk fat ratio, with similar structural behavior of lipids during digestion of both types of human milk being apparent. In contrast, differences in the colloidal structures were formed during digestion in the absence of bile salt because of a greater amount of FFAs being released from the nonpasteurized than pasteurized milks. This difference in FFAs released from both types of human milk could result in varying nutritional implications for infants.

Towards mesoporous silica as a pharmaceutical treatment for obesity - impact on lipid digestion and absorption.

Mesoporous silica particles (MSPs) are emerging as an interesting option to reduce calorific uptake as a treatment for obesity and other metabolic conditions. However, their further development under the pharmaceutical regulatory framework is hindered by poor understanding of the mechanisms by which they exert their effects. In the current study the interaction of MSPs with the lipid digestion process is investigated, specifically interactions with lipase enzymes and lipid digestion products as a key contributing factor to lipid absorption and calorific intake. The impact of exposing lipase to MSPs on the enzyme activity was assessed directly using the tributyrin digestion test. The extent of interaction of digestion products with MSPs was studied using selectively radiolabeled bile components and lipids, while the impact on in vivo absorption of lipids was studied by incorporation of radiolabelled lipid (triolein) into milk and administration with and without particles. The studies showed that particles that inhibited lipase activity also tended to interact more extensively with lipid digestion products. In vitro X-ray scattering studies revealed the interaction of some MSPs with lipid digestion products through changes in lipid self-assembly during digestion. The MSPs led to reduced lipid absorption in vivo compared to the control particles and MSP-free milk. While the specific properties of the MSPs that drive the differences between the behavior of MSPs during lipid digestion remain elusive, the studies highlight that interactions with the lipid digestion and absorption pathways are a likely mechanism for reducing calorific uptake.

Thiol-responsive lyotropic liquid crystals exhibit triggered phase re-arrangement and hydrogen sulfide (H2S) release.

Hydrogen sulfide (H2S) is an important signalling molecule with potential pharmaceutical applications. In pursuit of a suitable delivery system for H2S, herein we apply an amphiphilic trisulfide to concomitantly alter the mesophase behaviour of dispersed lipid particles and enable triggered H2S release. Amperometric release studies indicate the trisulfide acts as a sustained H2S donor, with inclusion into the mesophase attenuating release vs neat dispersed trisulfide. Taken together the results highlight the potential for including trisulfide-based additives in stimuli-responsive drug delivery vehicles.

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.

The effect of emulsifier type on the secondary crystallisation of monoacylglycerol and triacylglycerols in model dairy emulsions.

Dairy emulsions contain an intrinsically heterogeneous lipid phase, whose components undergo crystallisation in a manner that is critical to dairy product formulation, storage, and sensory perception. Further complexity is engendered by the diverse array of interfacially-active molecules naturally present within the serum of dairy systems, and those that are added for specific formulation purposes, all of which interact at the lipid-serum interface and modify the impact of lipid crystals on dairy emulsion stability. The work described in this article addresses this complexity, with a specific focus on the impact of temperature cycling and the effect of emulsifier type on the formation and persistence of lipid crystals at lipid-solution interfaces. Profile analysis tensiometry experiments were performed using single droplets of the low melting fraction of dairy lipids, in the presence and absence of emulsifiers (Tween 80 and whey protein isolate, WPI) and during the temperature cycling, to study the formation of monoacylglycerol (MAG) crystals at the lipid-solution interface. Companion experiments on the same lipid systems, and at the same cooling and heating rates, were undertaken with synchrotron small angle X-ray scattering, to specifically analyse the effect of emulsifier type on the formation of triacylglycerol (TAG) crystals at the lipid-solution interface of a model dairy emulsion. These two complementary techniques have revealed that Tween 80 molecules delay MAG and TAG crystal formation by lowering the temperature at which the crystallisation occurs during two cooling cycles. WPI molecules delay the crystallisation of MAGs and TAGs during the first cooling cycle, while MAG crystals form without delay during the second cooling cycle at the same temperature as MAG crystals in an emulsifier free system. The crystallisation of TAGs is inhibited during the second cooling cycle. The observed differences in crystallisation behaviour at the interface upon temperature cycling can provide further insight into the impact of emulsifiers on the long-term stability of emulsion-based dairy systems during storage.

The influence of lipid digestion on the fate of orally administered drug delivery vehicles.

This review will focus on orally administered lipid-based drug delivery vehicles and specifically the influence of lipid digestion on the structure of the carrier lipids and their entrained drug cargoes. Digestion of the formulation lipids, which are typically apolar triglycerides, generates amphiphilic monoglycerides and fatty acids that can self-assemble into a diverse array of liquid crystalline structures. Tracking the dynamic changes in self-assembly of the lipid digestion products during digestion has recently been made possible using synchrotron-based small angle X-ray scattering. The influence of lipid chain length and degree of unsaturation on the resulting lipid structuring will be described in the context of the critical packing parameter theory. The chemical and structural transformation of the formulation lipids can also have a dramatic impact on the physical state of drugs co-administered with the formulation. It is often assumed that the best strategy for drug development is to maximise drug solubility in the undigested formulation lipids and to incorporate additives to maintain drug solubility during digestion. However, it is possible to improve drug absorption using lipid digestion in cases where the solubility of the dosed drug or one of its polymorphic forms is greater in the digested lipids. Three different fates for drugs administered with digestible lipid-based formulations will be discussed: (1) where the drug is more soluble in the undigested formulation lipids; (2) where the drug undergoes a polymorphic transformation during lipid digestion; and (3) where the drug is more soluble in the digested formulation lipids.

Formation of Self-Assembled Mesophases During Lipid Digestion.

Lipids play an important role in regulating bodily functions and providing a source of energy. Lipids enter the body primarily in the form of triglycerides in our diet. The gastrointestinal digestion of certain types of lipids has been shown to promote the self-assembly of lipid digestion products into highly ordered colloidal structures. The formation of these ordered colloidal structures, which often possess well-recognized liquid crystalline morphologies (or "mesophases"), is currently understood to impact the way nutrients are transported in the gut and absorbed. The formation of these liquid crystalline structures has also been of interest within the field of drug delivery, as it enables the encapsulation or solubilization of poorly water-soluble drugs in the aqueous environment of the gut enabling a means of absorption. This review summarizes the evidence for structure formation during the digestion of different lipid systems associated with foods, the techniques used to characterize them and provides areas of focus for advancing our understanding of this emerging field.

Diffusion in Organic Film Stacks Containing Solution-Processed Phosphorescent Poly(dendrimer) Dopants.

Efficient organic light-emitting diodes (OLEDs) consist of an emissive layer comprising a blend of a light-emitting and host material in contact with one or more charge transporting layers. The distribution of the active material in the guest-host emissive layer blend and the changes that may occur upon thermal annealing are two important factors in determining the stability and efficiency of OLEDs. We have combined neutron reflectometry and photoluminescence measurements to investigate the structures of films comprising an emissive layer containing a phosphorescent poly(dendrimer) material blended with 4,4'-N,N'-di(carbazolyl)biphenyl. This combination has been shown to give rise to highly efficient OLEDs. Here, we show that the emissive poly(dendrimer) material was not uniformly distributed in the host, but formed a concentration gradient within the emissive layer. Upon heating, the adjacent electron transport layer was found to intermix with the emissive layer, accompanied by changes in the material distribution in the emissive layer. The intermixing of the materials led to a decrease in the photoluminescence from the poly(dendrimer) within the film. The decrease in the photoluminescence was ascribed to an increase in interchromophore interactions that could arise from a conformational change of the poly(dendrimer) or phase separation leading to aggregation. The results indicate that, while uniform mixing of the guest and host is not essential for efficiency, the thermal stabilities of both host and charge transport materials are important for device durability.