NMR chromatog. is a promising and superior alternative to NMR spectroscopy for analyzing mixts. since it simultaneously separates the spectra of the compds. and supplies information about their structure. This implies that there is no need for extn., purifn. or synthesis of stds., that are expensive, time consuming and usually impractical. The main aim of NMR chromatog. is to increase the differences in the diffusivities of different analytes in a mixt., allowing them to be more easily and reliably identified. The selection of surfactants and other components of microemulsions for the best performance as NMR chromatog. media was studied. Attention was focused on the selection of the proper cosolvent in three types of water-dilutable microemulsions: two anionic (deuterated ionic and the previously published fluorinated ionic) and one nonionic (undeuterated Tween-based). The diffusivities of several analytes are compared. The study also examines the effect of diln. and dets. the best compns. for the NMR chromatog. performance. For the anionic microemulsions, 1-butanol was found to be the most promising cosurfactant in the deuterated system 1-butanol-d10:toluene-d8:SDS-d25 in a 6:3:1 wt.-ratio dild. by D2O. This compn., dild. with a 85 wt% D2O, formed a microemulsion that was even stable at relatively elevated temps. (70 °C) and can serve as good medium for chromatog. NMR. Another possibility that was studied consists of nonionic-based microemulsions of iso-Pr alc. (IPA) in IPA:toluene:Tween 20 that could also be easily dild. indefinitely with water. IPA was found to be a very efficient cosurfactant at resolving diffusivities of all the components. However, the lack of availability of deuterated Tween makes it impractical for use as an NMR chromatog. formulation. [on SciFinder(R)]

Omega fatty acids, mainly the triglyceride of docosahexaenoic acid (TG-DHA), are considered important nutraceuticals. These compds. are water-insol. and their transport across membranes depends on their carriers. Dendrimers are known as drug carriers across cell membranes and also as permeation enhancers. The solubilization of TG-DHA and dendrimer into a microemulsion (ME) system serving as a carrier could be used for a targeted delivery in the future. The interactions between TG-DHA and second generation poly(propyleneimine) dendrimers (PPI-G2) and their effect on structural transitions of ME were explored along the water diln. line using ESR and pulsed-gradient spin-echo NMR along with other anal. techniques. The microviscosity, order parameter, and micropolarity of all studied systems decrease upon water diln. Incorporation of TG-DHA reduces the microviscosity, order, and micropolarity, whereas PPI-G2 leads to an increase in these parameters. The effect of PPI-G2 is more pronounced at relative high contents (1 and 5 wt%) where PPI-G2 interacts with the hydrophilic headgroups of the surfactants. In the macroscale, the effects of TG-DHA and PPI-G2 differ mostly in the bicontinuous region, where macroviscosity increases upon TG-DHA incorporation and decreases upon solubilization of 5 wt% PPI-G2. From DSC measurements it was concluded that in the presence of TG-DHA the PPI-G2 is intercalated easily at the interface. [on SciFinder(R)]

Double emulsions are emulsions in which an emulsion [water/oil (W/O) or oil/water] is dispersed in a continuous phase (water or oil, resp.), producing W/O/W or O/W/O. These systems have considerable potential in food systems, cosmetics, and pharmaceuticals. This entry reviews some studies and discusses the different approaches that have been introduced. The studies provide better understanding of the stabilizing mechanisms and pathways and a better control of the release patterns from double emulsions. [on SciFinder(R)]

In microemulsions, changes in droplet size and shape and possible transformations occur under various conditions. They are difficult to characterize by most analytical tools because of their nano-sized structure and dynamic nature. Several methods are usually combined to obtain reliable information, guiding the scientist in understanding their physical behavior. We felt that there is a need for a technique that complements those in use today in order to provide more information on the microemulsion behavior, mainly as a function of dilution with water. The improvement of NMR chemical shift measurements independent of bulk magnetization effects makes it possible to study the very weak intermolecular chemical shift effects. In the present study, we used NMR high resolution magic angle spinning to measure the chemical shift very accurately, free of bulk magnetization effects. The chemical shift of microemulsion components is measured as a function of the water content in order to validate the method in an interesting and promising, U-type dilutable microemulsion, which had been previously studied by a variety of techniques. Phase transition points of the microemulsion (O/W, bicontinuous, W/O) and changes in droplet shape were successfully detected using high-accuracy chemical shift measurements. We analyzed the results and found them to be compatible with the previous studies, paving the way for high-accuracy chemical shifts to be used for the study of other microemulsion systems. We detected two transition points along the water dilution line of the concentrate (reverse micelles) corresponding to the transition from swollen W/O nano-droplets to bicontinuous to the O/W droplets along with the changes in the droplets' sizes and shapes. The method seems to be in excellent agreement with other previously studied techniques and shows the advantage of this easy and valid technique. (C) 2014 Elsevier Inc. All rights reserved.

Cholesterol (CH) is a vital mol. for mammalian life. It functions as a precursor for a variety of biol. active mols. and as a moderator of membrane mobility, and has many other essential functions. However, a high blood CH level can cause development of cardiovascular diseases. The soln. for high CH level is an intake of CH-lowering drugs such as statins. Another option for lowering excess CH is intake of phytosterols (PS) as a nutraceutical, which reduces CH absorption in mammals. PS are sterols synthesized only in plants and are structurally similar to CH but with an extra hydrophobic carbon chain at the C-24 position. PS and CH both have low soly. in oil and even lower soly. in water. To improve the efficiency of PS in lowering CH level, it is important to develop suitable vehicles that will improve their solubilization and absorption. In this entry, we examine sterol-solubilization vehicles, which include micelles, emulsions, microemulsions, and bile salt (BS) systems. The discussion focuses on the solubilization capacity (SC) of the vehicles and their effect on the extent of CH absorption/inhibition. It can be concluded that the solubilized PS in these various vehicles enables a significant decrease in CH absorption in comparison to the intake of PS in its solid form. In addn., we shall review the competitive solubilization of CH and PS in microemulsion systems to understand the competitive solubilization mechanism, which has been proposed as one of the mechanisms for PS activity as a CH-lowering agent. [on SciFinder(R)]

This chapter summarizes the authors' efforts to develop modified microemulsions as nano-sized self-assembled liq. vehicles for the solubilization of nutraceuticals and to improve transmembrane transport for addnl. health benefits. Construction of U-type phase diagrams is essential for formulations of water-dilutable microemulsions. The solubilized active mols. are compds. with nutritional value to human health that are used in food applications. The chapter mentions a few such examples, such as lycopene, phytosterols, lutein, toco-pherols, CoQ10 , and essential oils. Some nutraceuticals are known to be practically insol. in water and, therefore, tablets or capsules that are taken orally tend to ppt. once the active ingredient is dild. with water. As a result, the bioavailability is very limited, and the adsorption from the intestine to the blood serum is poorly controlled. Water entrapped at the core of a w/o microemulsion can be bound to the surfactant head group that will restrict the water activity. [on SciFinder(R)]

Docosahexaenoic acid (DHA) promotes synthesis of anti-inflammatory prostaglandins and relief of dry eye symptoms. However, topical ophthalmic application of DHA is difficult because of its lipophilic property. Therefore, it is important to develop aqueous-based formulation with enhanced capabilities. Novel, unique water-dilutable microemulsions (MEs) were constructed to allow loading of naturally occurring rigid long-chain triglyceride of DHA (TG-DHA). The TG-DHA serves as solubilizate and as the oil phase, therefore preparation is poor in oil. The structural transformations of MEs upon water dilution were studied by SAXS, viscosity, electrical conductivity, self-diffusion NMR, DSC, cryo-TEM, and DLS techniques. At low water content a new type of water-in-oil (W/O) structure is formed. The glycerol/water phase hydrates the headgroups of surfactants, and the oil solvates their tails, forming ``ill-defined bicontinuous domains\''\. Upon further water dilution more structured bicontinuous domains of high viscosity are formed. After additional dilution, the mesophases invert to oil-in-water (O/W) droplets of similar to 8 nm. In the structures composed of up to 25 wt% water, the TG-DHA spaces and de-entangles the surfactant tails. Once the bicontinuous structures are formed, the surfactants and TG-DHA content decrease and their interfacial layer shrinks, leading to entanglement and buildup of viscous non-Newtonian mesophase. Above 70 wt% water TG-DHA is embedded in the core of the O/W droplets, and its effect on the droplets' structure is minimal. This new dilutable ill-defined microemulsion can be a potential delivery vehicle for ophthalmic TG-DHA transport. (C) 2015 Elsevier Inc. All rights reserved.

In this study we characterized a new and improved transport vehicle for 2,6-diisopropylphenol (propofol), a hydrophobic anesthesia drug, in the absence and presence of dendrimers being a transporting agents across cells, polypropylenimine (PPI) dendrimer generation 2 (PPI-G2) into a microemulsion (ME). Three unique systems of water-dilutable compositions capable of inverting from W/O to bicontinuous and to O/W structures upon water dilutions were studied by means of electrical conductivity, electron paramagnetic resonance (EPR), and self-diffusion nuclear magnetic resonance (SD-NMR). The microviscosity, as well as the order parameter (from EPR results) increase with the increase in the dendrimer content, while inverting the structures from W/O to bicontinuous ME. Inversion from the bicontinuous mesophase to the O/W nanodroplets caused a very minor increase in the order parameter. Self-diffusion NMR measurements provided information on the diffusivity and the interactions of the different components of the ME. It was found that propofol has no effect on the diffusivity of the components since it is embedded within the core of the ME droplets. However, the dendrimer increases the diffusivity of water. In addition, we learned that at high dendrimer content, it remains solubilized; however its location at the ME/water interface moves to the water continuous phase. The study demonstrates the ability of water dilutable MEs to act as drug carriers hosting both propofol and dendrimer. (C) 2016 Elsevier B.V. All rights reserved.

Molecular dynamics (MD) was employed by means of a specific simulation protocol to investigate the equilibrium structure at 25 A degrees C of the hexagonal inverted (H-II) mesophase composed from water, 1-monoolein (GMO), and tricaprylin, with or without entrapped lysozyme. Based on robust and fast MD simulations, the study provides a comprehensive analysis and visualization of the local structure of H-II mesophase containing admixtures. The most important physical insight is the possibility to observe the strong self-recovery capacity of the GMO layer, which allows the H-II mesophase tubes to reorganize and host lysozyme molecules with a size bigger than the diameter of the water channel. This is a direct message to the experimenters that the H-II mesophase has the potential to host molecules larger than the diameter of the water channel. Collective character of the interlipid interactions is outlined, which is not affected by the presence of the cargo and may be the reason for the efficient GMO reorganization. Another important result is the possible explanation of the role of triacylglycerols on the low-temperature stabilization of the H-II mesophase. The analysis shows that despite the low amount of tricaprylin, its molecules prevent the extreme inclination of the lipid tails and thus optimize the alignment capacity of the lipid tails layer. The study also reveals that the packing frustration does not depend on the temperature and the presence of admixtures. Hence, it might be numerically defined as a universal invariant parameter of a stable H-II mesophase composed of a certain lipid.

Riboflavin phosphate (RFP) is an essential compound in the treatment of keratoconus - a degenerative, non-inflammatory disease of the cornea. Currently, the quantitative and efficient transport of riboflavin to the cornea is possible after mechanical removal of the epithelium. To avoid surgical intervention, it is therefore important to develop a method for quantitatively transporting riboflavin across the intact epithelium. In the present study, an RFP-loaded microemulsion was prepared, which could potentially function as an ocular drug delivery system crossing the eye epithelium. The specially designed water-dilutable microemulsion was based on a mixture of nonionic surfactants. Propylene glycol and glycerol acted as cosurfactant and cosolvent assisting in the solubilization of the RFP. The glycerol-rich water-free concentrate consisted of direct micelles for which glycerol served as the hydrophilic phase. In formulations with up to 40 wt% water, the hydrophilic surfactant headgroups and glycerol strongly bind water molecules (DSC and SD-NMR). Above 60 wt% water, globular, O/W nanodroplets, 14 nm in diameter, are formed (SAXS, cryo-TEM, and SD-NMR). The structure of microemulsions loaded with 0.14-4.25 wt% RFP (0.29-8.89 mmol per 100 g formulation) is not significantly influenced by the presence of the RFP. However, in the microemulsions containing 10-80 wt% water, the mobility of RFP in the microemulsion is constrained by strong interactions with the surfactants and cosurfactant, and therefore free transport of the molecule can be achieved only upon higher (\textgreater80 wt%) water dilutions. (C) 2015 Elsevier Inc. All rights reserved.

The dielec. behavior of the insulin-loaded HII mesophase (contg. GMO-TAG-water-glycerol-insulin) was studied using two empty ref. systems (GMO-TAG-water and GMO-TAG-water-glycerol) at a frequency range of 10-2-106 Hz, and a temp. range of 290-333 K. Three clearly defined relaxation processes were obsd. and assigned to the reorientation of GMO polar heads, the tangential movement of counterions at the interface, and the movements of TAGs through the lipid tail. Upon addn. of glycerol, a heterogeneous inner structure was formed within the HII cylinders: the water-glycerol core surrounded by a water rigid layer. Upon heating, two crit. points were detected referring to the dehydration of the GMO heads (at 304 K, similar to the water-filled HII system) and to energetic modifications (at 316 K), resulting in breaking of the water layer allowing on-demand controlled release. Insulin incorporation combined the features of both ref. HII systems. Yet, unlike the empty HII systems, insulin perturbed the GMO-water interface while decreasing the movement of the GMO headgroup, and reducing T0 (296 K). No interactions were formed between the dipole of each counterion at the interface region and the matrix (the GMO), fitting the Debye process. Dynamic behavior was obsd., pointing to mobility between the hexagonal rods themselves, enabling controlled release from the HII carrier. [on SciFinder(R)]

The flow behavior and viscosity of TAGs contg. oleic and stearic acids were examd. in the liq. phase as well as at temps. close to the onset of crystn. by means of a temp.-controlled rheometer. Gelling and crystn. transitions were unambiguously identified by singularities in the viscosity vs. temp. curves of the TAGs. An addnl. transition between the gelling and onset of crystn. temps., attributed to the reorganization of the gel, was obsd. in the sym. TAGs only. The effect of the cooling rate, ranging between 0.1 and 5°C/min, was investigated. The flow behavior of the studied TAGs was shown to be strongly detd. by structural parameters (symmetry, degree of unsatn.). The flow behavior was also affected significantly by the cooling rate, suggesting that to certain extents the flow behavior detd. by structural parameters could be changed by manipulating the cooling rate. The study confirmed that TAG crystn. was initiated by and depends, at least in part, on complex mol. short range order transformations occurring in the melt. The findings of the study may be valuable for evaluating systems and equipment that were involved in the storage, handling and processing of materials incorporating these TAGs. [on SciFinder(R)]

Propofol (2,6-diisopropylphenol) is a drug for both induction and maintenance of anesthesia. Pure propofol cannot be injected because of its lipophilic character, low water-solubility, and low bioavailability. Presently, propofol is formulated in an unstable emulsion, easily oxidized, and easily contaminated with bacteria. We are proposing new, propofol-loaded modified microemulsions, stable thermodynamically, and microbiologically safe; the microemulsions are fully dilutable with water. Structural characterization of the empty and the propofol-loaded systems as a function of water dilution was accomplished using advanced analytical tools such as SD-NMR, SAXS, cryo-TEM, DSC, electrical conductivity, and viscosity. Upon water dilution the propofol-loaded concentrate forms swollen reverse micelles that upon further dilution (40 wt% water) progressively transform into a bicontinuous mesophase and then invert (\textgreater65 wt% water) into O/W nanodroplets without ``losing\''\ the solubilized propofol. The drug exhibits strong interactions with the surfactant (DSC and SD-NMR). Propofol increases the size of the microemulsion nanodroplets, but does not modify the microemulsion behavior. Water, ethanol, and PG are essential structural components, but do not interact directly with propofol. (C) 2015 Published by Elsevier B.V.

In the course of our studies on structured reverse lyotropic liquid crystals (LLC) as oleogels, a system was designed with the desired physical and rheology properties for cosmetic and pharmaceutical applications. The aqueous phase was partially replaced by glycerol to minimize bacteriological problems and obtain specific rheology characteristics. The constructed phase diagrams are based on ternary mixtures of glycerol monooleate (GMO), decane, water, and glycerol. The main lyotropic mesophase obtained in this study was reverse hexagonal derived from dilution line 8:2 (72 wt% GMO and 18 wt% decane) and 10 wt% water; or water:glycerol (wt ratios 3:1 and 1:1) mixture. It was found that heat-cool fluctuation caused formation of new pseudo-equilibrium structures with mesomorphic transformations to more fluid and less ordered mesostructures. Replacing up to 50 wt% of the water by glycerol significantly increases the gel phase region in the phase diagram, meaning more structural compositional options. The structural parameters were determined using cross-polarized light microscopy (CPLM), differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), and small angle X-ray scattering (SAXS). Rheological measurements revealed viscoelastic properties of lyotropic liquid crystals with a decrease in the elasticity (G'), plasticity (GaEuro(3)), and complex viscosity (eta\*\), as a function of increasing the glycerol content.

Two non-steroidal anti-inflammatory drugs (NSAIDs), sodium diclofenac (Na-DFC) and celecoxib (CLXB) were solubilized within cubic and lamellar mesophases as carriers for transdermal drug delivery. SD-NMR, SAXS, ATR-FTIR, and EPR measurements were performed to examine the systems' characteristics and the interactions between the drugs and their hosting mesophases. The amphiphilic drug Na-DFC was found to incorporate at the interfaces of the cubic and lamellar mesophases and thus to act as a cosurfactant and a "structure stabilizer". It increased the order degree and the interactions between the GMO mols. and led the systems toward denser packing. CLXB exhibits an opposite effect on the mesophases. Its solubilization within both systems is accompanied with significant channel swelling and decrease in the order degree. The hydrophobic, rigid and bulky CLXB behaves as a "structure breaker", incorporated between the GMO tails, disturbing the mesophase packing and enhancing the repulsion at the tails region, limiting their close binding. Release expts. from Franz cells revealed that Na-DFC release is dependent on the quantity of water within the hosting mesophase as the water-rich formulation exhibits 1.5-fold enhancement in the release of the drug, compared to the lamellar phase. In contrast, CLXB release was not influenced by the water quantity, hinting that the release mechanisms of the drugs are different while Na-DFC diffuses from the water channels to the external phase, CLXB diffusion occurs through the continuous lipophilic region. The difference in the solubilization sites and interactions of each drug with the mesophases affect their release profiles and det. the preferred formulations for each drug's delivery vehicle. [on SciFinder(R)]

Sodium diclofenac (Na-DFC) and celecoxib (CLXB) are common nonsteroidal anti-inflammatory (NSAID) drugs which suffer from poor bioavailability and severe side effects when consumed orally, and their transdermal delivery might present important advantages. In this study, the drugs were solubilized in cubic and lamellar mesophases as transdermal delivery vehicles, and a cell-penetrating peptide, HIV-TAT (TAT), was examd. as a skin penetration enhancer. SD-NMR, ATR-FTIR, and EPR measurements revealed that, in the cubic mesophase (which is rich in water content), TAT populates the aq. cores and binds water, while in the dense lamellar system (with the lower water content) TAT is bound also to the glycerol monooleate (GMO) and increases the microviscosity and the order degree. TAT secondary structure in the cubic system was found to be a random coil while once it was embedded in the closely packed lamellar system it transforms to a more ordered compact state of $\beta$-turns arranged around the GMO headgroups. TAT remarkably increased the diffusion of Na-DFC and CLXB from the cubic systems by 6- and 9-fold enhancement, resp. TAT effect on drug diffusion from the lamellar systems was limited to an increase of 1.3- and 1.7-fold, resp. The dense packing and strong binding in the lamellar phase led to slow diffusion rates and slower drug release in controlled pattern. These effects of the chem. compn. and vehicle geometry on drug diffusion are demonstrated with the impacts of TAT which can be specifically utilized for controlling skin delivery of drugs as required. [on SciFinder(R)]

The phase composition of triacylglycerols (TAG) is determined by chemical structure and is greatly affected by kinetics. Positional isomerism and unsaturation are two key structural elements that govern, for a large part, the phase behavior of TAG during crystallization. Polymorphism, thermal properties, and microstructure of dioleoyl-stearoyl isomers (OSO, SOO) were investigated at different cooling rates with XRD, DSC and PLM techniques, respectively. The physical properties of the symmetrical TAG were found to predictably vary with cooling rate; whereas, the properties of the asymmetrical TAG remained relatively constant. This was explained to be mainly due to the extra steric hindrance caused by asymmetry and the disturbances introduced at the ``terrace\''\ level via methyl-end group interactions. The findings underscore the intricate contribution of saturation and symmetry to the phase trajectories of diunsaturated TAG. The knowledge gained will help understand the behavior of more complex materials and can be used for the manipulation of fat structures at different length scales and direct the manufacture of novel food systems and other relevant materials.

The prepn. of org.-inorg. composite coatings with the purpose to increase the bioactivity of bioinert metal implants was investigated. As substrates, glass plates and rough titanium surfaces (Ti-SLA) were employed. The method comprises the deposition of polyelectrolyte multilayers (PEMLs) followed by immersion of the coated substrate into a calcifying soln. of low supersatn. (MCS). Single or mixed PEMLs were constructed from poly-L-lysine (PLL) alternating with poly-L-glutamate, (PGA), poly-L-aspartate (PAA), and/or chondroitin sulfate (CS). ATR-FTIR spectra reveal that (PLL/PGA)10 multilayers and mixed multilayers with a (PLL/PGA)5 base contain intermol. $\beta$-sheet structures, which are absent in pure (PLL/PAA)10 and (PLL/CS)10 assemblies. All PEML coatings had a grainy topog. with aggregate sizes and size distributions increasing in the order: (PLL/PGA)n \textless (PLL/PAA)n \textless (PLL/CS)n. In mixed multilayers with a (PLL/PGA)n base and a (PLL/PAA)n or (PLL/CS)n top, the aggregate sizes were greatly reduced. The PEMLs promoted calcium phosphate nucleation and early crystal growth, the intensity of the effect depending on the compn. of the terminal layer(s) of the polymer. In contrast, crystal morphol. and structure depended on the supersatn., pH, and ionic strength of the MCS, rather than on the compn. of the org. matrix. Crystals grown on both uncoated and coated substrates were mostly platelets of calcium deficient carbonate apatite, with the Ca/P ratio depending on the pptn. conditions. [on SciFinder(R)]

The effect of second, third, and fifth generations of poly(propylene imine) glycodendrimers-open maltose shell (PPI-Mal) on reverse hexagonal (HII) mesophase and on the release of sodium diclofenac (Na-DFC) drug was investigated. The HII mesophase comprised glycerol monooleate (GMO)/tricaprylin (TAG) in a wt. ratio of 90/10 and 20 wt. % water (+0.5 wt. % PPI-Mal of each generation) without or with 0.25 wt. % (Na-DFC). The microstructural characteristics of these systems were detd. by small-angle X-ray scattering; attenuated total reflectance Fourier transform IR was used to characterize the mol. level interactions and the location of the PPI-Mal. Third-and fifth-generation PPI-Mal, because of their maltose groups, interact mainly with the bulk water within the cylinders of the HII and strongly bind the water mols., as manifested by the decrease in the lattice parameter and dehydration of the lipid headgroups. Co-solubilization of Na-DFC with the third and fifth generations caused competition of the two host compds. for water binding and induced relocation of the drug from the bulk water to the GMO-water interface. In vitro release of Na-DFC from the HII showed that the release process was faster in the systems with third- and fifth-generation PPI-Mal compared with the control and second-generation systems. [on SciFinder(R)]

Self-assembled lyotropic liquid crystals (LLCs) of lipids and water are interesting mesophases that can be considered among other applications as delivery vehicles due to their remarkable structural complexity. The phase behavior of mixtures of glycerol monooleate (monoolein, GMO) and phytantriol were particularly well studied in drug delivery systems, food products, and encapsulation and crystallization of proteins. We are summarizing in this chapter our contribution to modified LLCs and their structural features and recent systematic efforts to utilize them for solubilization, and potential release of drugs and biomacromolecules. Some of the most interesting applications are the implementation of peptides and proteins in the reversed cubic and hexagonal mesophases, to enhance penetrating pattern of a model drugs. LLC vehicles were shown to allow ``on demand'' targeted release, based on controlling the polymorphism of lyotropic liquid crystalline mesophases. A new pathway to responsive LLCs, enabling the controlled release of hydrophilic drugs diffusing through the water channels of the mesophases was also investigated. The system is capable of self-assembling into a reverse bicontinuous cubic phase of Im3m symmetry and transform into a reverse columnar hexagonal as a function of pH, pressure or enzymes. LLCs were shown to entrap several peptides enzymes, proteins and nucleotides into cubic and lamellar monoolein-based mesophases in order to protect them and enable their release. The main outcomes of the described research demonstrated that control of the physical properties of hexagonal LLC on different length scales is key for rational design of these systems as delivery vehicles for both low molecular weight therapeutics and biomacromolecules.