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.

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 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)]

In this paper the cosolubilization of 2nd, 3rd, and 4th generations of polypropyleneimine (PPI: PPI-G2, -G3, and -G4) dendrimers with sodium diclofenac (Na-DFC) into reverse gyroid cubic (QG) liq. crystals is reported. Structural properties and interactions of PPI dendrimers with and without the drug were studied using small-angle X-ray scattering, attenuated total reflected Fourier transform IR (ATR-FTIR) spectroscopy, and differential scanning calorimetry (DSC) measurements. Incorporation of PPI-G2 (without Na-DFC) into QG mesophase led to a decrease of 78 \AA in the lattice parameter. Solubilization of higher PPI generations, G3 and G4, led to increases in the lattice parameter to 57 \AA and 64 \AA, resp. At 25 wt%, each of the dendrimers caused a phase transition QG → reverse hexagonal (HII). According to ATR-FTIR and DSC, the large lattice parameter values of G3 and G4 (relative to G2) embedment were assigned to their interactions with the carboxyl groups of GMO at the interface in comparison to the strong interaction of PPI-G2 with the water. Cosolubilization of Na-DFC with PPI-G2 revealed enlargement of the lattice parameter (of the new HII mesophase), while in the case of G3 and G4 systems no significant influence was seen with Na-DFC. The release of Na-DFC from QG and HII systems was followed by UV-vis spectroscopy and revealed generation-dependence on drug release. As dendrimer generation increased, the cumulative drug release decreased. [on SciFinder(R)]

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 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)]

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.

The study investigates the unit cell structure of inverted hexagonal (HII) mesophase composed of monoolein (1-monoolein, GMO) and water using atomistic mol. dynamics methods without imposing any restraints on lipid and water mols. Statistically meaningful and very contrast images of the radial mass d. distribution, scrutinizing also the sep. components water, monoolein, the polar headgroups of the lipids, the double bond, and the termini of the hydrocarbon chain (the tail), are obtained. The lipid/water interface structure is analyzed based on the obtained water d. distribution, on the estd. no. of hydrogen bonds per monoolein headgroup, and on the headgroup-water radial distribution functions. The headgroup mass d. distribution demonstrates hexagonal shape of the monoolein/water interface that is well-defined at higher water/monoolein ratios. Water interacts with the headgroups by forming a three-layer diffusive mass d. distribution, and each layer's shape is close to hexagonal, which is an indication of long-range structural interactions. It is found that the monoolein headgroups form a const. no. of hydrogen bonds leaving an excessive amt. of water mols. outside the first lipid coordination sphere. Furthermore, the quantity of water at the monoolein/water interface increases steadily upon extension of the unit cell, so the interface should have a very dynamic structure. Investigation of the hydrocarbon residues reveals high compression and well-expressed structuring of the tails. The tails form a very compressed and constrained structure of defined layers across the unit cell with properties corresponding to a more densely packed nonpolar liq. (oil). Due to the hexagonal shape the 2D packing frustration is const. and does not depend on the water content. All reported structural features are based on averaging of the at. coordinates over the time-length of the simulation trajectories. That kind of processing allows the observation of the water/GMO interface shape and its stability and mobility at a time scale close to the ones of the intermol. interactions. [on SciFinder(R)]

Cartilage and/or bone tissue engineering is a very challenging area in modern medicine. Since cartilage is an avascular tissue with limited capacity for self-repair, using scaffolds provides a promising option for the repair of severe cartilage damage caused by trauma, age-related degeneration, and/or diseases. Our aim in this study was to design a model for a functional biomedical membrane to form the interface between a cartilage-forming scaffold and bone. To realize such a membrane gelatin gels contg. calcium or phosphate ions were exposed from one side to a soln. of the other constituent ion (i.e., a sodium phosphate soln. was allowed to diffuse into a calcium-contg. gel and vice versa). The partially calcified gels were analyzed by XRD, ATR-FTIR spectra, E-SEM, and EDX. Thus, we confirmed the existence of a gradient of crystals, with a dense top layer, extending several micrometers into the gel. XRD spectra and Ca/P at. ratios confirmed the existence of calcium deficient apatites. The effect of different exptl. parameters on the calcification process within the gelatin membranes has been elucidated. It was shown that increasing the gelatin concn. from 5 wt % to 10 wt. % retards calcification. A similar effect was obsd. when glycerol, which is frequently used as plasticizer, was added to the system. With increasing calcium concn. within the org. matrix, the quantity and d. of calcium phosphate crystals over/within the gel increased. The possible explanations for the above phenomena are discussed. [on SciFinder(R)]

The role of 2nd generation polypropyleneimine (PPIG2) dendrimer in controlling the release of gallic acid (GA) as a model drug from lyotropic liq. crystal was explored. GA (0.2 wt%) was solubilized in three types of mesophases: lamellar (L$\alpha$), cubic (space group of Ia3d, QG), and reverse hexagonal (HII), composed of GMO and water (and D-$\alpha$-tocopherol, or tricaprylin in the case of HII mesophases). Small angle X-ray scattering (SAXS) and attenuated total reflectance Fourier transform IR (ATR-FTIR) along with UV spectrophotometry were utilized to elucidate the structure modifications and release resulting from the cosolubilization of GA and PPIG2. Solubilization of PPIG2 into L$\alpha$ and QG phases caused transformation of both structures to HII. The diffusion of GA out of the mesophases was found to be dependent on water content and PPIG2 concn. Rapid release from L$\alpha$ + PPIG2 and QG + PPIG2 mesophases was recorded. The release from both HII mixts. (with D-$\alpha$-tocopherol and tricaprylin) was shown to be dependent on the type of oil. Release studies conducted for 72 h showed that GA release can be modulated and sustained by the presence of PPIG2, supposedly due to the electrostatic interactions between the dendrimer and the drug mol. [on SciFinder(R)]

Pure satd. triacylglycerols (TAGs) in canola oil were used as model systems to analyze oil loss in structured oil both from thermodn. and kinetic perspectives. Two important parameters which effectively and predictively measure the relative propensity of a solid network to lose/hold oil were defined: (1) the rate of oil loss, K, which is a quantified representation of the kinetics of oil loss and (2) the initial amt. of oil susceptible to be lost, i.e., the propensity for oil loss (POL), which is a representation of the thermodn. of oil binding. It was found that the POL and K values do not always trend in the same fashion, suggesting that the mechanism of oil binding is complex, depending on the structurant's cryst. form locked within the oil network. The two parameters were, however, correlated to the melting and thermal behavior of the structurants, to the polymorphic structures that are obtained during the cooling process and to the habit (shape, size and morphol.) of the cryst. phase in the oil. Both POL and K had a strong correlation to the oil loss. [on SciFinder(R)]

The usual treatment of hypercholesterolemia includes a class of drugs known as statins (simvastatin among them), which inhibit the prodn. of cholesterol. Another way of reducing cholesterol levels is with the use of phytosterols, which reduce the transport of exogenic cholesterol from the intestine into the blood stream. The 2 treatments can be combined, achieving an additive effect. However, both simvastatin and phytosterols are practically insol. in water, and therefore their absorption and activity are low. Nanosized self-assembled structured liq. systems are modified microemulsions that present an alternative pathway for improving the bioavailability of poorly water-sol. drugs. The goal of this study was to solubilize the maximal quantity of both simvastatin and phytosterols in a single, fully dilutable microemulsion system. The authors constructed a water-dilutable liq. drug delivery system that includes sucrose monolaurate, propylene glycol, and oleyl lactate. This system exhibits high solubilization capacity for both simvastatin (7.0 wt%) and phytosterols (3.5 wt%) when each is solubilized sep. in a water-free conc. When simvastatin and phytosterols were solubilized together at a wt ratio of 2.5:1, max. solubilization was obtained with 4.7 wt% simvastatin and 1.9 wt% phytosterols. Structural and anal. methods were applied including rheol., DSC, SD-NMR, SAXS, and cryo-TEM. The water-free "conc." consisted of direct micelles for which propylene glycol served as the hydrophilic phase. Upon water diln., the direct micelles appear to form "lipophilic compds. dispersed in hydrophilic continuous phase". The solubilizates are located in the droplet core and/or at the interface. [on SciFinder(R)]

A review. This article reviews the creation of advanced drug delivery nano systems (aDDnSs) comprised of liposomes and polymers focusing on the interactions of the structural components and their biomedical applications. ADDnSs have been shown to significantly: (a) increase the load of the bioactive substance into the system, which is very important both for manufg.-economic reasons and for toxicity reasons (as less quantity of carrier is used for the same amt. of drug), (b) lower the release rate of the encapsulate drug, a fact that could create a more controlled and/or sustained release profile of the drug in the bloodstream, leading to lower toxicity and higher effectiveness (c) advanced pharmacol. toxicity compared to the free drug and at least equal toxicity compared to the resp. conventional liposomal formulation. A plethora of physicochem. data has begun to shed light to the interactions of the components of these complicate systems that seem to be responsible for the advantages presented by the aDDnSs. [on SciFinder(R)]