Adsorption and Desorption of Bile Salts at Air–Water and Oil–Water Interfaces

Bile Salts (BS) adsorb onto emulsified oil droplets to promote lipolysis and then desorb, solubilizing lipolytic products, a process which plays a crucial role in lipid digestion. Hence, investigating the mechanism of adsorption and desorption of BS onto the oil–water interface is of major importance to understand and control BS functionality. This can have implications in the rational design of products with tailored digestibility. This study shows the adsorption and desorption curves of BS at air–water and oil–water interfaces obtained by pendant drop tensiometry. Three BS have been chosen with different conjugation and hydroxyl groups: Sodium Taurocholate (NaTC), Glycodeoxycholate (NaGDC) and Sodium Glycochenodeoxycholate (NaGCDC). Experimental results show important differences between the type of BS and the nature of the interface (air/oil–water). At the air–water interface, Glycine conjugates (NaGDC and NaGCDC) are more surface active than Taurine (NaTC), and they also display lower surface tension of saturated films. The position of hydroxyl groups in Glycine conjugates, possibly favors a more vertical orientation of BS at the surface and an improved lateral packing. These differences diminish at the oil–water interface owing to hydrophobic interactions of BS with the oil, preventing intermolecular associations. Desorption studies reveal the presence of irreversibly adsorbed layers at the oil–water interface in all cases, while at the air–water interface, the reversibility of adsorption depends strongly on the type of BS. Finally, dilatational rheology shows that the dilatational response of BS is again influenced by hydrophobic interactions of BS with the oil; thus, adsorbed films of different BS at the oil–water interface are very similar, while larger differences arise between BS adsorbed at the air–water interface. Results presented here highlight new features of the characteristics of adsorption layers of BS on the oil–water interface, which are more relevant to lipid digestion than characteristics of BS adsorbed at air–water interfaces.MCIN/AEI/10.13039/501100011033Project PID2020-116615RAI00Biocolloid and Fluid Physics Group (ref. PAIFQM115) of the University of Granada (Spain)MDPI and University of Granada

Condensation of Model Lipid Films by Cholesterol: Specific Ion Effects

The condensing effect and the ability of cholesterol (CHOL) to induce ordering in lipid films is a question of relevance in biological membranes such as the milk fat globule membrane (MFGM) in which the amount of CHOL influences the phase separation and mechanical resistance to rupture of coexisting phases relevant to emulsified food systems. Here, we study the effect of different salts (NaCl, CaCl2, MgCl2, LaCl3) on monolayers made of a model mixture of lipids (DPPC:DPPS 4:1) and CHOL. To this end, we apply Langmuir Film Balance to report a combined analysis of surface pressure-area (pi-A) and surface potential-area (DV–A) isotherms along with Micro-Brewster Angle Microscopy (Micro-BAM) images of the monolayers in the presence of the different electrolytes. We show that the condensation of lipid by CHOL depends strongly on the nature of the ions by altering the shape and features of the pi-A isotherms. DV–A isotherms provide further detail on the ion specific interactions with CHOL. Our results show that the condensation of lipids in the presence of CHOL depends on the combined action of ions and CHOL, which can alter the physical state of the monolayer.This research was funded by “Ministerio de Economía y Competitividad (MINECO), Plan Nacional de Investigación, Desarrollo e Innovación Tecnológica (I + D + i)”: Grant RYC-2012-10556, Projects MAT2015-63644-C2-1-R, RTI2018-101309-B-C21 and FIS2016-80087-C2-1-P, and European Regional Development Fund (ERDF). “Universidad de Granada” CEI-BIOTIC-BS14.2015. This study was also partially supported by “Consejería de Conocimiento, Investigación y Universidad, Junta de Andalucía”, ref. SOMM17/6105/UGR and SOMM17/6109/UGR

Complexation of DNA with Thermoresponsive Charged Microgels: Role of Swelling State and Electrostatics

This research was funded by projects RTI2018-101309-B-C21 and PID2020-631-116615RA-I00, funded by MCIN/AEI/10.13039/501100011033 and by "ERDF A way of making Europe" and by project PY20_00138, funded by Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades (PAIDI2020).Micro- and nanogels are being increasingly used to encapsulate bioactive compounds. Their soft structure allows large loading capacity while their stimuli responsiveness makes them extremely versatile. In this work, the complexation of DNA with thermoresponsive microgels is presented. To this end, PEGylated charged microgels based on poly-N-isopropylacrylamide have been synthesized, allowing one to explore the electrostatics of the complexation. Cationic microgels complexate spontaneously by electrostatic attraction to oppositely charged DNA as demonstrated by electrophoretic mobility of the complexes. Then, Langmuir monolayers reveal an increased interaction of DNA with swollen microgels (20 degrees C). Anionic microgels require the presence of multivalent cations (Ca2+) to promote the complexation, overcoming the electrostatic repulsion with negatively charged DNA. Then again, Langmuir monolayers evidence their complexation at the surface. However, the presence of Ca2+ seems to induce profound changes in the interaction and surface conformation of anionic microgels. These alterations are further explored by measuring adsorbed films with the pendant drop technique. Conformational changes induced by Ca2+ on the structure of the microgel can ultimately affect the complexation with DNA and should be considered in the design. The combination of microstructural and surface properties for microgels offers a new perspective into complexation of DNA with soft particles with biomedical applications.MCIN/AEI RTI2018-101309-B-C21 PID2020-631-116615RA-I00Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades PY20_0013

Specific Ion Effects in Cholesterol Monolayers

The interaction of ions with interfaces and, in particular, the high specificity of these interactions to the particular ions considered, are central questions in the field of surface forces. Here we study the effect of different salts (NaI, NaCl, CaCl2 and MgCl2) on monolayers made of cholesterol molecules, both experimentally (surface area vs. lateral pressure isotherms measured by a Langmuir Film Balance) and theoretically (molecular dynamics (MD) all-atomic simulations). We found that surface isotherms depend, both quantitatively and qualitatively, on the nature of the ions by altering the shape and features of the isotherm. In line with the experiments, MD simulations show clear evidences of specific ionic effects and also provide molecular level details on ion specific interactions with cholesterol. More importantly, MD simulations show that the interaction of a particular ion with the surface depends strongly on its counterion, a feature ignored so far in most theories of specific ionic effects in surface forces

Identification of the thistle milk component Silibinin(A) and Glutathione-disulphide as potential inhibitors of the pancreatic lipase: Potential implications on weight loss

This work has been supported by Ministerio de Ciencia e Innovacion de Espana (under project RTI2018101309BC21) , by the Fundacion Seneca del Centro de Coordinacion de la Investigacion de la Region de Murcia (under Project 20988/PI/18) and by a grant from Ministerio de Economia y Competitividad de Espana (CTQ201787974R) . This research was partially supported by the supercomputing infrastructure of Poznan Supercomputing Centre, and by the einfrastructure program of the Research Council of Norway, and the supercomputer centre of UiTthe Arctic University of Norway. The authors also thankfully acknowledge the computer resources and the technical support provided by the Plataforma Andaluza de Bioinformatica of the University of Malaga. Powered@NLHPC: This research was partially supported by the supercomputing infrastructure of the NLHPC (ECM02)Peripheral targets like pancreatic-lipase appear to be the most suitable pharmacological alternative for obesity, as with orlistat, although its adverse effects limit its use. Therefore, the aim of this work was to identify new natural compounds able to inhibit pancreatic-lipase in an in vitro model. The DrugBank database was used to perform docking calculations. The best fitting-score compounds were further evaluated in vitro. Our data revealed that glutathione-disulphide (GSSG) and silibinin(A) inhibit pancreatic-lipase. This was confirmed by measuring hydrolysis in an emulsion model, obtaining that the suppression of lipid digestion by silibinin(A) was higher than that of GSSG and close to the effect of orlistat. Combined analysis established the existence of different inhibition mechanisms for each compound. In summary, silibinin(A) and GSSG inhibited pancreatic-lipase and, therefore, may be served as promise natural compounds to face with obesity. Further studies comprise the next step to fully validate the suitability of these compounds.Spanish Government RTI2018-101309-B-C21Fundacion Seneca 20988/PI/18Ministerio de Economia y Competitividad de Espana CTQ2017-87974-RSupercomputing infrastructure of Poznan Supercomputing CentreEinfrastructure program of the Research Council of NorwaySupercomputer centre of UiTthe Arctic University of NorwaySupercomputer centre of UiTthe Arctic University of Norwa

pH influences the interfacial properties of blue whiting (M. poutassou) and whey protein hydrolysates determining the physical stability of fish oil-in-water emulsions

This work was funded by the project CTQ2017-87076-R from the Spanish Ministry of Science and Innovation. Julia Maldonado-Valderrama and Teresa del Castillo-Santaella acknowledge financialsupport from project RTI2018-101309-B-C21. The authors are also very grateful to F. Javier Espejo-Carpio and Marta Padial-Dominguez for providing the whey and blue whiting protein hydrolysates. Funding for open access charge: Universidad de Granada/CBUA.This work investigates the influence of the interfacial properties of whey protein (WPH) and blue whiting protein (BPH) hydrolysates on the physical stability of fish oil-in-water emulsions stabilized with these hydrolysates at pH 2 or 8. Measurements of interfacial tension and dilatational rheology confirmed that pH is a key factor affecting these interfacial properties of WPH and BPH. WPH, when tested at 1 and 10 mg/mL, showed a higher interfacial activity at pH 8 when compared to pH 2 or to BPH at pH 8 or 2, despite having a lower protein content. Moreover, when tested at 0.1 and 1 mg/mL, the dilatational modulus of WPH was significantly higher at pH 8 than at pH 2. These findings correlate with the formation of smaller oil droplets and a more resistant interfacial peptide layer for WPH at pH 8, hence explaining the improved physical stability of the 5% fish oil-in water emulsion stabilized with WPH at pH 8. BPH did not show significant differences in interfacial activity with pH but exhibited significantly higher dilatational elasticity and viscosity at pH 2 compared to pH 8 (when measured at 0.1 mg/mL and 0.01 or 0.1 Hz). This correlates with the formation of stable 5% fish oil-in-water emulsions with BPH at pH 2 but not at pH 8.Spanish Government CTQ2017-87076-

Formulation, Colloidal Characterization, and In Vitro Biological Effect of BMP-2 Loaded PLGA Nanoparticles for Bone Regeneration

The following are available online at https://www.mdpi.com/1999-4923/11/8/388/s1, Figure S1. Scheme of the formulation of NP-BMP2; Figure S2: Scheme of the protein adsorption process for NP-BSA-BMP2; Video S1. NTA experiments for NP-BMP2; Video S2. NTA experiments for empty NPs.Nanoparticles (NPs) based on the polymer poly (lactide-co-glycolide) acid (PLGA) have been widely studied in developing delivery systems for drugs and therapeutic biomolecules, due to the biocompatible and biodegradable properties of the PLGA. In this work, a synthesis method for bone morphogenetic protein (BMP-2)-loaded PLGA NPs was developed and optimized, in order to carry out and control the release of BMP-2, based on the double-emulsion (water/oil/water, W/O/W) solvent evaporation technique. The polymeric surfactant Pluronic F68 was used in the synthesis procedure, as it is known to have an effect on the reduction of the size of the NPs, the enhancement of their stability, and the protection of the encapsulated biomolecule. Spherical solid polymeric NPs were synthesized, showing a reproducible multimodal size distribution, with diameters between 100 and 500 nm. This size range appears to allow the protein to act on the cell surface and at the cytoplasm level. The effect of carrying BMP-2 co-adsorbed with bovine serum albumin on the NP surface was analyzed. The colloidal properties of these systems (morphology by SEM, hydrodynamic size, electrophoretic mobility, temporal stability, protein encapsulation, and short-term release profile) were studied. The effect of both BMP2-loaded NPs on the proliferation, migration, and osteogenic differentiation of mesenchymal stromal cells from human alveolar bone (ABSC) was also analyzed in vitro.This research was funded by the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía (Spain) through research groups FQM-115 and CTS-1028, by the following research project: MAT2013-43922-R—European FEDER support included—(MICINN, Spain) and by MIS Ibérica S.L

Effect of Hyaluronic Acid and Pluronic-F68 on the Surface Properties of Foam as a Delivery System for Polidocanol in Sclerotherapy

The use of foams to deliver bioactive agents and drugs is increasing in pharmaceutics. One example is the use of foam as a delivery system for polidocanol (POL) in sclerotherapy, with the addition of bioactive compounds to improve the delivery system being a current subject of study. This work shows the influence of two bioactive additives on the structure and stability of POL foam: hyaluronic acid (HA) and Pluronic-F68 (F68). HA is a natural non-surface-active biopolymer present in the extracellular matrix while F68 is a surface-active poloxamer that is biocompatible with plasma-derived fluids. Both additives increase the bulk viscosity of the sample, improving foam stability. However, HA doubled and F68 quadruplicated the foam half lifetime of POL. HA reduced the size and polydispersity of the bubble size distribution and increased the surface elasticity with respect to POL. Both facts have a positive impact in terms of foam stability. F68 also altered bubble structure and increased surface elasticity, again contributing to the enhancement of foam stability. The surface characterization of these systems is important, as in foam sclerotherapy it is crucial to assure the presence of POL at the surface of the bubbles in order to deliver the sclerosant agent in the target vein.Junta de Andalucia NANOFOAM-PI12.2956Instituto de Salud Carlos III Spanish Government MAT2017-82182-R RTI2018-101309-B-C21Consejeria de Economia, Conocimiento, Empresas y UniversidadEuropean Union (EU) SOMM17/6109/UG

Applications of serum albumins in delivery systems: Differences in interfacial behaviour and interacting abilities with polysaccharides

One of the major applications of SerumAlbumins is their use as delivery systems for lipophilic compounds in biomedicine. Their biomedical application is based on the similarity with Human Serum Albumin (HSA), as a fully biocompatible protein. In general, Bovine Serum Albumin (BSA) is treated as comparable to its human homologue and used as a model protein for fundamental studies since it is available in high amounts and well understood. This protein can act as a carrier for lipophilic compounds or as protective shell in an emulsion-based vehicle. Polysaccharides are generally included in these formulations in order to increase the stability and/or applicability of the carrier. In this review, themain biomedical applications of Albumins as drug delivery systems are first presented. Secondly, the differences between BSA andHSA are highlighted, exploring the similarities and differences between these proteins and their interaction with polysaccharides, both in solution and adsorbed at interfaces. Finally, the use of Albumins as emulsifiers for emulsion-based delivery systems, concretely as Liquid Lipid Nanocapsules (LLNs), is revised and discussed in terms of the differences encountered in the molecular structure and in the interfacial properties. The specific case of Hyaluronic Acid is considered as a promising additivewith important applications in biomedicine. The literatureworks are thoroughly discussed highlighting similarities and differences between BSA and HSA and their interaction with polysaccharides encountered at different structural levels, hence providing routes to control the optimal design of delivery systems.This work has been funded by the following projects, which are gratefully acknowledged: MAT2017-82182-R and RTI2018-101309-BC21 (Ministerio de Ciencia e Innovación). The authors also acknowledge “Mancomunidad de los Pueblos de la Alpujarra Granadina” for the funds raised and supplied for this research

Macromolecular design of folic acid functionalized amylopectin- albumin core-shell nanogels for improved physiological stability and colon cancer cell targeted delivery of curcumin

Nanogels have potential for encapsulating cancer therapeutics, yet their susceptibility to physiological degradation and lack of cellular specificity hinder their use as effective oral delivery vehicles. Herein, we engineered novel albumin-core with folic acid functionalized hyperbranched amylopectin shell-type nanogels, prepared through a two-step reaction and loaded with curcumin while the proteinaceous core was undergoing thermal gelation. The nanogels had a mean hydrodynamic diameter of ca. 90 nm and ζ-potential of ca. -24 mV. Encapsulation of curcumin within the nanogels was restored, up to ca. 0.05 mg mL-1, beyond which, a gradual increase in size and a decrease in ζ-potential was observed. The core-shell structures were resilient to in vitro physiological oral-gastrointestinal digestion owing to a liquid crystalline B- and V-type polymorphism in the polysaccharide shell, the latter being driven by the shell functionalization with folic acid. Additionally, these biocompatible nanogels restored stability of the encapsulated curcumin and exhibited augmented cellular uptake and retention specifically in folate receptor-positive HT29 human colon adenocarcinoma cells, inducing early-stage apoptosis. Novel insights from this study represent a promising platform for rational designing of future oral delivery systems that can surmount physiological barriers for delivering cancer therapeutics to colon cancer cells with improved stability and specificity