Whey Protein Isolate as a Substrate to Design Calendula officinalis Flower Extract Controlled-Release Materials.

The use of natural active substances and the development of new formulations are promising directions in the cosmetic and pharmacy industries. The primary purpose of this research was the production of microparticles based on whey protein isolate (WPI) and calcium alginate (ALG) containing Calendula officinalis flower extract and their incorporation into films composed of gelatin, WPI, and glycerol. Both swollen and dry microparticles were studied by optical microscopy and their sizes were measured. Water absorption by the microparticles, their loading capacity, and the release profile of flower extract were also characterized. The films were analyzed by mechanical tests (Young's modulus, tensile strength, elongation at break), swelling capacity, contact angle, and moisture content measurements. The presented data showed that the active ingredient was successfully enclosed in spherical microparticles and completely released after 75 min of incubation at 37 °C. The incorporation of the microparticles into polymer films caused a decrease in stiffness and tensile strength, simultaneously increasing the ductility of the samples. Moreover, the films containing microparticles displayed higher swelling ability and moisture content compared to those without them. Hence, the materials prepared in this study with Calendula officinalis flower extract encapsulated into polymeric microspheres can be a starting point for the development of new products intended for skin application; advantages include protection of the extract against external factors and a controlled release profile.

From Supramolecular Hydrogels to Multifunctional Carriers for Biologically Active Substances.

Supramolecular hydrogels are 3D, elastic, water-swelled materials that are held together by reversible, non-covalent interactions, such as hydrogen bonds, hydrophobic, ionic, host-guest interactions, and metal-ligand coordination. These interactions determine the hydrogels' unique properties: mechanical strength; stretchability; injectability; ability to self-heal; shear-thinning; and sensitivity to stimuli, e.g., pH, temperature, the presence of ions, and other chemical substances. For this reason, supramolecular hydrogels have attracted considerable attention as carriers for active substance delivery systems. In this paper, we focused on the various types of non-covalent interactions. The hydrogen bonds, hydrophobic, ionic, coordination, and host-guest interactions between hydrogel components have been described. We also provided an overview of the recent studies on supramolecular hydrogel applications, such as cancer therapy, anti-inflammatory gels, antimicrobial activity, controlled gene drug delivery, and tissue engineering.

Evaluation of Polymeric Matrix Loaded with Melatonin for Wound Dressing.

The development of scaffolds mimicking the extracellular matrix containing bioactive substances has great potential in tissue engineering and wound healing applications. This study investigates melatonin-a methoxyindole present in almost all biological systems. Melatonin is a bioregulator in terms of its potential clinical importance for future therapies of cutaneous diseases. Mammalian skin is not only a prominent melatonin target, but also produces and rapidly metabolizes the multifunctional methoxyindole to biologically active metabolites. In our methodology, chitosan/collagen (CTS/Coll)-contained biomaterials are blended with melatonin at different doses to fabricate biomimetic hybrid scaffolds. We use rat tail tendon- and Salmo salar fish skin-derived collagens to assess biophysical and cellular properties by (i) Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), (ii) thermogravimetric analysis (TG), (iii) scanning electron microscope (SEM), and (iv) proliferation ratio of cutaneous cells in vitro. Our results indicate that melatonin itself does not negatively affect biophysical properties of melatonin-immobilized hybrid scaffolds, but it induces a pronounced elevation of cell viability within human epidermal keratinocytes (NHEK), dermal fibroblasts (NHDF), and reference melanoma cells. These results demonstrate that this indoleamine accelerates re-epithelialization. This delivery is a promising technique for additional explorations in future dermatotherapy and protective skin medicine.

A Look at the Spatial Confining Effect on the Molecular Electrostatic Potential (MEP)-A Case Study of the HF and BrCN Molecules.

In this theoretical study, we report on the molecular electrostatic potential (MEP) of titled molecules confined by repulsive potentials of cylindrical symmetry mimicking a topology. Our calculations show that the spatial restriction significantly changes the picture of the MEP of molecules in a quantitative and qualitative sense. In particular, the drastic changes in the MEP as a function of the strength of spatial confinement are observed for the BrCN molecule. This preliminary study is the first step in the investigation of the behavior of the MEP of molecular systems under orbital compression.

DFT and spatial confinement: a benchmark study on the structural and electrical properties of hydrogen bonded complexes.

An extended set of 37 exchange correlation functionals, representing different DFT approximations, has been evaluated on a difficult playground represented by the dipole moment (µz), polarizability (αzz), first hyperpolarizability (ßzzz), and the corresponding interaction-induced electrical properties (Δµz, Δαzz, Δßzzz) of spatially confined hydrogen bonded (HB) dimers. A two-dimensional harmonic oscillator potential was used to exert the effect of spatial restriction. The performance of DFT methods in predicting hydrogen bond lengths in the studied molecular complexes upon confinement has also been examined. The data determined using a high-level CCSD(T) method serve as a reference. The conducted analyses allow us to conclude that methods rooted in DFT constitute a precise tool for the calculation of µz and αzz as well as Δµz and Δαzz, as most of the tested functionals provide results affected by rather small relative errors. On the other hand, an accurate description of the nonlinear optical response of the studied HB systems remains a great challenge for most of the analyzed DFT functionals, both in vacuum and in the presence of an analytical confining potential. Some of the tested DFT methods are found to be prone to catastrophic failure in the prediction of ßzzz as well as Δßzzz. The obtained results indicate that there is no great chasm in performance between functionals belonging to different DFT approximations or functionals including different amount of Hartree-Fock exchange when the values of dipole moment and first hyperpolarizability as well as the corresponding interaction-induced electrical properties are considered. However, a higher fraction of Hartree-Fock exchange improves the quality of predictions of αzz and Δαzz. Additionally, it has been shown that only three functionals from the examined set, namely B2PLYP, B3LYP and ωB97X-D, provide highly accurate structural parameters for the investigated systems. Of significant importance is the conclusion that the ωB97X-D functional, representing a modern and highly parametrized range-separated hybrid, demonstrates the most coherent behavior, showing rather small deviations from the reference data in the case of µz, αzz, Δµz and Δαzz as well as the structural parameters of the studied HB dimers. Moreover, our results indicate that the presence of spatial confinement has a rather small effect on the performance of DFT methods.

Assessment of DFT for endohedral complexes' dipole moment: PNO-LCCSD-F12 as a reference method.

We present a systematic evaluation of the performance of a wide range of exchange-correlation functionals and related dispersion correction schemes for the computation of dipole moments of endohedral complexes, formed through the encapsulation of an AB molecule (AB = LiF, HCl) inside carbon nanotubes (CNTs) of different diameter. The consistency and accuracy of (i) generalized gradient approximation, (ii) meta GGA, (iii) global hybrid, and (iv) range-separated hybrid density functionals are assessed. In total, 37 density functionals are tested. The results obtained using the highly accurate pair natural orbitals based explicitly correlated local coupled cluster singles doubles (PNO-LCCSD-F12) method of Werner and co-workers [Schwilk et al., J. Chem. Theory Comput., 2017, 13, 3650; Ma et al., J. Chem. Theory Comput., 2017, 13, 4871] with the aug-cc-pVTZ basis set serve as a reference. The static electric dipole moment is computed via the finite field response or, when possible, as the expectation value of the dipole operator. Among others, it is shown that functionals belonging to the class of range-separated hybrids, provide results closest to the coupled cluster reference data. In particular, the ωB97X as well as the M11 functional may be considered as a promising choice for computing electric properties of noncovalent endohedral complexes. On the other hand, the worst performance was found for the functionals which do not include the Hartree-Fock exchange. The analysis of both the coupled cluster and the DFT results indicates a strong coupling of dispersion and polarization that may also explain why lower level DFT methods, as well as Hartree-Fock and MP2, cannot yield dipole moments beyond a qualitative agreement with the higher order reference data. Interestingly, the much smaller and less systematically constructed basis sets of Pople of moderate size provide results of accuracy at least comparable with the extended Dunning's aug-cc-pVTZ basis set.

Vibrational nonlinear optical properties of spatially confined weakly bound complexes.

This study focuses on the theoretical description of the influence of spatial confinement on the electronic and vibrational contributions to (hyper)polarizabilities of two dimeric hydrogen bonded systems, namely HCNHCN and HCNHNC. A two-dimensional analytical potential is employed to render the confining environment (e.g. carbon nanotube). Based on the results of the state-of-the-art calculations, performed at the CCSD(T)/aug-cc-pVTZ level of theory, we established that: (i) the influence of spatial confinement increases with increasing order of the electrical properties, (ii) the effect of spatial confinement is much larger in the case of the electronic than vibrational contribution (this holds for each order of the electrical properties) and (iii) the decrease in the static nuclear relaxation first hyperpolarizability upon the increase of confinement strength is mainly due to changes in the harmonic term, however, in the case of nuclear relaxation second hyperpolarizability the anharmonic terms contribute more to the drop of this property.

Two-photon absorption of the spatially confined LiH molecule.

In the present contribution we study the influence of spatial restriction on the two-photon dipole transitions between the X1Σ+ and A1Σ+ states of lithium hydride. The bond-length dependence of the two-photon absorption strength is also analyzed for the first time in the literature. The highly accurate multiconfiguration self-consistent field (MCSCF) method and response theory are used to characterize the electronic structure of the studied molecule. In order to render the effect of orbital compression we apply a two-dimensional harmonic oscillator potential, mimicking the topology of cylindrical confining environments (e.g. carbon nanotubes, quantum wires). Among others, the obtained results provide evidence that at large internuclear distances the TPA response of lithium hydride may be significantly enhanced and this effect is much more pronounced upon embedding of the LiH molecule in an external confining potential. To understand the origin of the observed variation in the two-photon absorption response a two-level approximation is employed.

About the nature of halogen bond interaction under the spatial confinement.

Nowadays, much attention is put toward the description of noncovalent complexes exposed to the high pressure or embedded in confining environments. Such conditions may strongly modify the physical and chemical properties of molecular systems. This study focuses on the theoretical description of the confinement induced changes in geometry and energetic parameters of the halogen bonded FCl⋯CNF complex. A model analytical potential is applied to render the effect of orbital compression. In order to analyze the nature of halogen bond interaction, in the presence of spatial confinement, the supermolecular approach together with the symmetry-adapted perturbation theory is used. Furthermore, a thorough analysis of topological parameters, characterizing the halogen bond upon orbital compression, is performed within the quantum theory of atoms in molecules. The calculations are carried out using the ωB97x and CCSD(T) methods in connection with the aug-cc-pVTZ basis set. Among others, the obtained results indicate that the spatial confinement not only modifies the nature of halogen bond interaction but also induces the appearance of a completely new form of the studied FCl⋯CNF system.

Combined systems approaches reveal highly plastic responses to antimicrobial peptide challenge in Escherichia coli.

Obtaining an in-depth understanding of the arms races between peptides comprising the innate immune response and bacterial pathogens is of fundamental interest and will inform the development of new antibacterial therapeutics. We investigated whether a whole organism view of antimicrobial peptide (AMP) challenge on Escherichia coli would provide a suitably sophisticated bacterial perspective on AMP mechanism of action. Selecting structurally and physically related AMPs but with expected differences in bactericidal strategy, we monitored changes in bacterial metabolomes, morphological features and gene expression following AMP challenge at sub-lethal concentrations. For each technique, the vast majority of changes were specific to each AMP, with such a plastic response indicating E. coli is highly capable of discriminating between specific antibiotic challenges. Analysis of the ontological profiles generated from the transcriptomic analyses suggests this approach can accurately predict the antibacterial mode of action, providing a fresh, novel perspective for previous functional and biophysical studies.

Hydrogen bonding inside and outside carbon nanotubes: HF dimer as a case study.

In this theoretical work we analyze the noncovalent interactions of molecular complexes formed between the hydrogen bonded HF dimer and single-walled carbon nanotubes (SWCNTs) of different diameters. In particular, the interaction energies of: (i) spatially confined hydrogen fluoride molecules and (ii) HF dimer and the exterior or interior of SWCNTs are investigated. The computations are carried out in a supermolecular manner using the M06-2X exchange-correlation functional. In order to establish the influence of mutual orientation of the hydrogen fluoride dimer and molecular carbon cages on the analyzed energetic parameters energy scans are performed. Furthermore, changes in the charge distribution of the investigated endo- and exohedral complexes are studied employing the Natural Bond Orbital analysis. Among others, the position of the HF dimer with respect to the carbon cages proves to have a significant influence on the analyzed quantities. The results of our study also indicate that the HF dimer interacts stronger with the interior rather than the exterior of SWCNTs. Moreover, a substantial enhancement of the basis set superposition error is disclosed.

Hydrogen-bonded complexes upon spatial confinement: structural and energetic aspects.

In the present study we consider structural and energetic aspects of spatial confinement of the H-bonded systems. The model dimeric systems: HF···HF, HCN···HCN and HCN···HCCH have been chosen for a case study. Two-dimensional harmonic oscillator potential, mimicking a cylindrical confinement, was applied in order to render the impact of orbital compression on the analyzed molecular complexes. The calculations have been performed employing the MP2 method as well as the Kohn-Sham formulation of density functional theory. In the latter case, two exchange-correlation potentials have been used, namely B3LYP and M06-2X. The geometries of studied complexes have been optimized (without any constraints) in the presence of the applied model confining potential. A thorough analysis of topological parameters characterizing hydrogen bonds upon orbital compression has been performed within the Quantum Theory of Atoms in Molecules (QTAIM). Furthermore, an energetic analysis performed for the confined H-bonded complexes has shown a different trend in the interaction energy changes. Additionally, a variational-perturbational decomposition scheme was applied to study the interaction energy components in the presence of spatial confinement.

Unveiling new genetic insights in rheumatoid arthritis for drug discovery through Taxonomy3 analysis.

Genetic support for a drug target has been shown to increase the probability of success in drug development, with the potential to reduce attrition in the pharmaceutical industry alongside discovering novel therapeutic targets. It is therefore important to maximise the detection of genetic associations that affect disease susceptibility. Conventional statistical methods such as genome-wide association studies (GWAS) only identify some of the genetic contribution to disease, so novel analytical approaches are required to extract additional insights. C4X Discovery has developed Taxonomy3, a unique method for analysing genetic datasets based on mathematics that is novel in drug discovery. When applied to a previously published rheumatoid arthritis GWAS dataset, Taxonomy3 identified many additional novel genetic signals associated with this autoimmune disease. Follow-up studies using tool compounds support the utility of the method in identifying novel biology and tractable drug targets with genetic support for further investigation.

Conformational flexibility determines selectivity and antibacterial, antiplasmodial, and anticancer potency of cationic α-helical peptides.

We used a combination of fluorescence, circular dichroism (CD), and NMR spectroscopies in conjunction with size exclusion chromatography to help rationalize the relative antibacterial, antiplasmodial, and cytotoxic activities of a series of proline-free and proline-containing model antimicrobial peptides (AMPs) in terms of their structural properties. When compared with proline-free analogs, proline-containing peptides had greater activity against Gram-negative bacteria, two mammalian cancer cell lines, and intraerythrocytic Plasmodium falciparum, which they were capable of killing without causing hemolysis. In contrast, incorporation of proline did not have a consistent effect on peptide activity against Mycobacterium tuberculosis. In membrane-mimicking environments, structures with high α-helix content were adopted by both proline-free and proline-containing peptides. In solution, AMPs generally adopted disordered structures unless their sequences comprised more hydrophobic amino acids or until coordinating phosphate ions were added. Proline-containing peptides resisted ordering induced by either method. The roles of the angle subtended by positively charged amino acids and the positioning of the proline residues were also investigated. Careful positioning of proline residues in AMP sequences is required to enable the peptide to resist ordering and maintain optimal antibacterial activity, whereas varying the angle subtended by positively charged amino acids can attenuate hemolytic potential albeit with a modest reduction in potency. Maintaining conformational flexibility improves AMP potency and selectivity toward bacterial, plasmodial, and cancerous cells while enabling the targeting of intracellular pathogens.

Stability Studies, Biodegradation Tests, and Mechanical Properties of Sodium Alginate and Gellan Gum Beads Containing Surfactant.

The excessive presence of single-use plastics is rapidly degrading our natural environment on a global scale due to their inherent resistance to decomposition. Wet wipes used for personal or household purposes contribute significantly to the accumulation of plastic waste. One potential solution to address this problem involves developing eco-friendly materials that possess the ability to degrade naturally while retaining their washing capabilities. For this purpose, the beads from sodium alginate, gellan gum, and a mixture of these natural polymers containing surfactant were produced using the ionotropic gelation method. Stability studies of the beads by observing their appearance and diameter were performed after incubation in solutions of different pH values. The images showed that macroparticles were reduced in size in an acidic medium and swelled in solution of pH-neutral phosphate-buffered saline. Moreover, all the beads first swelled and then degraded in alkaline conditions. The beads based on gellan gum and combining both polymers were the least sensitive to pH changes. The compression tests revealed that the stiffness of all macroparticles decreased with the increasing pH of the solutions in which they were immersed. The studied beads were more rigid in an acidic solution than in alkaline conditions. The biodegradation of macroparticles was assessed using a respirometric method in soil and seawater. It is important to note that the macroparticles degraded more rapidly in soil than in seawater.

Gelatin and gelatin/starch-based films modified with sorbitol for wound healing.

Gelatin-based films modified with sorbitol were produced from gelatin solution or gelatin/starch blends using a simple and low-cost solvent casting method, and subsequently, their physicochemical, mechanical, and biocompatibility properties were characterized. This work focused on developing and optimizing a biopolymeric blend to improve the pure biopolymers' properties for potential biomedical applications such as wound dressing. The films were characterized in terms of morphology and transparency, mechanical, moisture and swelling properties, thermal stability, and degradation potential. Moreover, hemocompatibility, as well as cytocompatibility of prepared films, were examined. The addition of sorbitol contributed to improving mechanical properties, swelling reduction, and increasing biostability over time. The cytocompatibility of obtained films was confirmed in vitro with two different human cell lines, fibroblastic and osteoblastic, and a more favorable cellular response was received for fibroblasts. Further, in hemocompatibility studies, it was found that all films may be classified as non-hemolytic as they did not have a negative effect on the human erythrocytes. The obtained results indicate the great potential of the gelatin/starch blends modified with sorbitol as regenerative biomaterials intended for wound healing applications.

Electric dipole (hyper)polarizabilities of spatially confined LiH molecule.

In this study we report on the electronic contributions to the linear and nonlinear static electronic electric dipole properties, namely the dipole moment (µ), the polarizability (α), and the first-hyperpolarizability (ß), of spatially confined LiH molecule in its ground X (1)Σ(+) state. The finite-field technique is applied to estimate the corresponding energy and dipole moment derivatives with respect to external electric field. Various forms of confining potential, of either spherical or cylindrical symmetry, are included in the Hamiltonian in the form of one-electron operator. The computations are performed at several levels of approximation including the coupled-cluster methods as well as multi-configurational (full configuration interaction) and explicitly correlated Gaussian wavefunctions. The performance of Kohn-Sham density functional theory for the selected exchange-correlation functionals is also discussed. In general, the orbital compression effects lead to a substantial reduction in all the studied properties regardless of the symmetry of confining potential, however, the rate of this reduction varies depending on the type of applied potential. Only in the case of dipole moment under a cylindrical confinement a gradual increase of its magnitude is observed.

Structural contributions to the intracellular targeting strategies of antimicrobial peptides.

The interactions of cationic amphipathic antimicrobial peptides (AMPs) with anionic biological membranes have been the focus of much research aimed at improving the activity of such compounds in the search for therapeutic leads. However, many of these peptides are thought to have other polyanions, such as DNA or RNA, as their ultimate target. Here a combination of fluorescence and circular dichroism (CD) spectroscopies has been used to assess the structural properties of amidated versions of buforin II, pleurocidin and magainin 2 that support their varying abilities to translocate through bacterial membranes and bind to double stranded DNA. Unlike magainin 2 amide, a prototypical membrane disruptive AMP, buforin II amide adopts a poorly helical structure in membranes closely mimicking the composition of Gram negative bacteria, such as Escherichia coli, and binds to a short duplex DNA sequence with high affinity, ultimately forming peptide-DNA condensates. The binding affinities of the peptides to duplex DNA are shown to be related to the structural changes that they induce. Furthermore, CD also reveals the conformation of the bound peptide buforin II amide. In contrast with a synthetic peptide, designed to adopt a perfect amphipathic alpha-helix, buforin II amide adopts an extended or polyproline II conformation when bound to DNA. These results show that an alpha-helix structure is not required for the DNA binding and condensation activity of buforin II amide.

Design of Sodium Alginate/Gelatin-Based Emulsion Film Fused with Polylactide Microparticles Charged with Plant Extract.

This study aimed at designing emulsion films based on sodium alginate, gelatin, and glycerol, and their modification by the addition of lipids (cottonseed oil and beeswax). Film composition with the most promising properties was further modified by the incorporation of polylactide (PLA) microparticles with Calendula officinalis flower extract. PLA microspheres were obtained by the emulsion/solvent evaporation method. The size distribution of oily particles in emulsions was investigated. Mechanical properties, moisture content, UV-Vis spectra, and the color of films were analyzed, while biophysical skin parameters were assessed after their application to the skin. Moreover, the contact angles were measured, and the surface free energy of polymeric films was determined. An investigation of the amount of Calendula officinalis flower extract which can be incorporated into PLA microparticles was performed. The modification of the composition of films significantly influenced their physicochemical properties. The selected active ingredient in the form of plant extract was successfully incorporated into polymeric microparticles that were further added into the developed emulsion film. The condition of the skin after the application of obtained emulsion films improved. The prepared materials, especially containing microparticles with plant extract, can be considered for designing new cosmetic forms, such as cosmetic masks, as well as new topical formulations for pharmaceutical delivery.

Lyophilized Emulsions in the Form of 3D Porous Matrices as a Novel Material for Topical Application.

Researchers are constantly searching for innovations that can be applied to the cosmetic industry. Production of porous materials stored in a lyophilized form and swollen directly before use may be beneficial considering their facilitated packaging, transport and storage. In this study, we propose porous materials based on sodium alginate, gelatin, glycerol and lipids (cottonseed oil and beeswax) obtained by freeze-drying and cross-linking. Material composition with the most promising properties was modified by the addition of PLA microparticles with Calendula officinalis flower extract. The structure and properties of obtained porous materials were analyzed. ATR-FTIR, mechanical properties, residual moisture content, porosity and density were assessed, as well as swelling properties and degradation after their cross-linking. The loading capacity and in vitro release of Calendula officinalis flower extract were performed for samples with incorporated PLA microparticles containing plant extract. The modification of the composition and fabrication method of materials significantly influenced their physicochemical properties. The selected plant extract was successfully incorporated into polymeric microparticles that were subsequently added into developed materials. Prepared materials may be considered during designing new cosmetic formulations.