Metal Ions Can Modulate the Self-Assembly and Activity of Catalytic Peptide Amyloids.

Rational design of peptides has become a powerful tool to produce self-assembled nanostructures with the ability to catalyze different chemical reactions, paving the way to develop minimalistic enzyme-like nanomaterials. Catalytic amyloid-like assemblies have emerged among the most versatile and active, but they often require additional factors for activity. Elucidating how these factors influence the structure and activity is key for the design. Here, we showed that biologically relevant metal ions can guide and modulate the self-assembly of a small peptide into diverse amyloid architectures. The morphology and catalytic activity of the resulting fibrils were tuned by the specific metal ion decorating the surface, whereas X-ray structural analysis of the amyloids showed ion-dependent shape sizes. Molecular dynamics simulations showed that the metals can strongly affect the local conformational space, which can trigger major rearrangements of the fibrils. Our results demonstrate that the conformational landscape of catalytic amyloids is broad and tunable by external factors, which can be critical for future design strategies.

Influence of the crystallinity on the physicochemical properties of spray-dried quercetin-inulin microparticles and their performance during in vitro digestion.

Encapsulation of quercetin (Q) with inulin (In) by spray-drying was performed applying a Box-Behnken design where the effect of the inlet air temperature, percentage of inulin crystallite dispersion and Q content were studied on the crystallinity index (CI). Three microparticle systems with CI between 2 % and 20 % (Q-In-2 %, Q-In-12 % and Q-In-20 %) were selected to study the CI effect on Q release during an in vitro digestion. The higher the CI of microparticles, the higher the encapsulation efficiency (76.4 %, Q-In-20 %). Surface quercetin was steadily released during the oral, gastric, and intestinal phases of the digestion. The CI of the microparticles did not influence the Q bioaccessibility values (23.1-29.7 %). The highest Q delivery occurred during the simulated colonic phase (44.4-66.4 %) due to the action of the inulinase. The controlled crystallization in spray-dried microparticles is a promising strategy for the designing of polyphenol-based microparticles with specific delivery properties.

Incorporation of hydroxytyrosol alkyl esters of different chain length as antioxidant strategy in walnut oil spray-dried microparticles with a sodium alginate outer layer.

Omega-3 rich vegetable oils, such as walnut oil, are gaining interest because of their health benefits. Synthetized homologous series of hydroxytyrosol alkyl esters (HTEs) with different alkyl chain lengths (C4-C18) were incorporated in purified walnut oil (PWO) spray-dried microparticles, designed with Capsul® (C) as encapsulating agent and sodium alginate (SA) as outer layer (PWO-C/SA). The encapsulation efficiency (>87%) and Tg of PWO-C/SA microparticles were not affected by the HTEs. The incorporation of HTE-C10 increased the melting point (185.0 ± 1.3 °C), decreasing the formation of Dimers + Polymers (1.12 ± 0.05% at day 35 of storage) and the crystallinity of the microparticles (>170 °C). The highest stability of PWO-C(HTE-C10)/SA suggests a specific location of HTE-C10 at the oil:water interface. The SA layer delayed the release of fatty acids during in vitro digestion. The incorporation of HTEs of medium chain length can be a suitable strategy to protect unsaturated oils encapsulated by spray-drying.

Soybean oil organogelled emulsions as oral delivery systems of hydroxytyrosol and hydroxytyrosol alkyl esters.

Water-in-soybean oil organogelled emulsions (OGEs) were formulated as fat replacers and evaluated as delivery systems of hydroxytyrosol (HT, hydrophilic compound), hydroxytyrosol octanoate (HTC18, hydrophobic compound) and hydroxytyrosol decanoate (HTC10, with intermediate hydrophobicity and the highest antioxidant activity measured by conjugated autoxidizable triene assay). OGEs formulated with 55% of water and a ternary blend of candelilla wax, fully hydrogenated palm oil and monoacylglycerols showed mechanical properties similar to lard and solid-like behavior. The increase in the water content, together with a higher concentration of structuring agents in the oil phase, led to an increase in oil retention capacity and texture parameters. A slight desesterification of HTC10 and HTC18 was found during in vitro gastrointestinal digestion. The three bioactive compounds loaded in OGEs showed high bioaccessibility values (∼84%) at the end of digestion, regardless their chain length and hydrophobicity. These OGEs designed as fat replacers showed a great potential for vehiculation of both hydrophilic and lipophilic compounds.

Influence of the Location of Ascorbic Acid in Walnut Oil Spray-Dried Microparticles with Outer Layer on the Physical Characteristics and Oxidative Stability.

Purified walnut oil (PWO) microparticles with Capsul® (C, encapsulating agent), sodium alginate (SA) as outer layer and ascorbic acid (AA) as oxygen scavenger were obtained by spray drying using a three-fluid nozzle. AA was incorporated in the inner infeed (PWO-C(AA)/SA), in the outer infeed (PWO-C/SA(AA)) and in both infeed (PWO-C(AA)/SA(AA)). PWO-C(AA)/SA (4.56 h) and POW-C(AA)/SA(AA) (2.60 h) microparticles showed higher induction period than POW-C/SA(AA) (1.17 h), and lower formation of triacylglycerol dimers and polymers during storage (40 °C). Therefore, AA located in the inner infeed improved the oxidative stability of encapsulated PWO by removing the residual oxygen. AA in the SA outer layer did not improve the oxidative stability of encapsulated PWO since oxygen diffusion through the microparticles was limited and/or AA weakened the SA layer structure. The specific-location of AA (inner infeed) is a strategy to obtain stable spray-dried polyunsaturated oil-based microparticles for the design of foods enriched with omega-3 fatty acids.

Delivery of ionizable hydrophilic drugs based on pharmaceutical formulation of ion pairs and ionic liquids.

New therapeutics such as antisense oligonucleotides, small interfering RNA and peptide-drug conjugates are taking great relevance in the pharmaceutical industry due to their specificity of action and their improved safety profile. However, they could present bioavailability issues due to their hydrophilic nature, such as BCS class III drugs. Therefore, the formation of ion pairs of these type of molecules allows modifying their physicochemical characteristics such as polarity and lipophilicity leading to improved permeability. By carrying out a tailored synthesis, it is possible to obtain complexes with greater stability and better performance in vitro and in vivo, where their correlation with physicochemical properties continues to be a growing field of research. Moreover, ionic liquids (IL), which are substances that melt below 100 °C, have enabled modifying various drug properties, showing promising results in vitro-in vivo, especially when they are included in suitable drug delivery systems, such as nanoparticles, microparticles, self-emulsifying drug delivery systems, and transdermal patches, among others. The drug-IL is formed from the therapeutic agent and a counterion, mainly by ionic interactions, and resulting in a wide variety of derivatives with different properties. However, the pharmaceutical field is limited to the use of some excipients or GRAS (generally recognized as safe) substances, so the search for new counterions is of great interest. In this article, we have compiled key indexes that can be obtained from databases to guide the search for suitable counterions, together with different drug delivery system strategies to choose the most appropriate formulation according to the non-parenteral route of administration selected. Intellectual property advancements in the field are also presented and analyzed.

Effect of Adding Curcumin on the Properties of Linseed Oil Organogels Used as Fat Replacers in Pâtés.

Beeswax-based organogels were formulated with linseed oil and curcumin according to a statistical design to increase the oxidative stability of spreadable meat products (pâté) where these organogels (OGCur) were incorporated as fat substitutes. The organogels obtained under optimal conditions (9.12% beeswax, 0.54% curcumin) showed a mechanical strength similar to pork backfat determined by back extrusion and high oil binding capacity (OBC; over 90%). The incorporation of curcumin at this concentration did not lead to any change in the arrangement of the crystal network, OBC, and mechanical, thermal, or rheological properties of the organogels. Beeswax organogels with and without curcumin, with a ß' orthorhombic subcell structure, showed a predominant elastic behavior and a melting event wider and shifted to lower temperatures than pure beeswax, suggesting a plasticizer effect of the oil in the wax crystals. The oxidative stability of the organogels under accelerated oxidation conditions increased due to the incorporation of curcumin. A decrease in the curcumin content was found from day 4 at 60 °C, together with a significantly lower formation of both peroxides and malonaldehyde. When pork backfat was partially or totally replaced by OGCur in pâtés, a noticeable protective effect of curcumin against lipid oxidation was found during chilled storage.

Influence of the Physical State of Spray-Dried Flavonoid-Inulin Microparticles on Oxidative Stability of Lipid Matrices.

The effect of the physical state of flavonoid-inulin microparticles (semi-crystalline/amorphous) on the oxidative stability of lipid matrices was studied. Epicatechin (E) and quercetin (Q) microparticles with inulin were formulated at two infeed temperatures (15 °C and 90 °C) by spray drying. X-ray diffraction analyses showed that flavonoid-inulin microparticles obtained at feed temperature of 15 °C were semi-crystalline (E-In-15, 61.2% and Q-In-15, 60%), whereas those at 90 °C were amorphous (Q-In-90, 1.73 and Q-In-90 2.30%). Semi-crystalline state of flavonoid-inulin microparticles enhanced the EE (68.8 and 67.8% for E and Q, respectively) compared to amorphous state (41.6 and 51.1% for E and Q, respectively). However, amorphous Q-microparticles showed the highest antioxidant activity both in methyl linoleate and sunflower oil, increasing the induction period and decreasing the polar compounds and polymer triglyceride formation during long-term oxidation study. Therefore, the physical state of spray-dried flavonoid-inulin microparticles may determine their antioxidant activity in lipid matrices.

Er-Doped Nanostructured BaTiO3 for NIR to Visible Upconversion.

Photoluminescent mechanisms in erbium-doped barium titanate nanoparticle systems were studied. Er3+ ions were introduced into the BaTiO3 lattice by the sol-gel method. The resulting Er3+ concentration was between 0% and 5%, with Ba/Ti ratios of 1.008 and 0.993. The stoichiometry of Ba and Ti concentrations in the lattice influenced the doping mechanism and placement of erbium ions in the lattice structure. Our research shows the existence of a strong correlation between Ba/Ti ratios, erbium concentration, phase structure and doping site location on the upconversion photoluminescence mechanisms. Competing upconversion emissions ²H11/2/4S3/2→4I15/2 at 523 and 548 nm respectively and other photoluminescent mechanisms as 4I9/2→4I11/2 around 4000 nm (2500 cm-1) were studied using Raman and emission spectroscopy. The upconversion process is predominant over other photoluminescent decay when the material presents high distortion in the surrounding activator.