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Botulinum neurotoxins (BoNTs), produced by the spore-forming bacterium Clostridium botulinum, cause botulism, a rare but fatal illness affecting humans and animals. Despite causing a life-threatening disease, BoNT is a multipurpose therapeutic. Nevertheless, as the most potent natural toxin, BoNT is classified as a Select Agent in the US, placing C. botulinum research under stringent governmental regulations. The extreme toxicity of BoNT, its impact on public safety, and its diverse therapeutic applications urge to devise safe solutions to expand C. botulinum research. Accordingly, we exploited CRISPR/Cas9-mediated genome editing to introduce inactivating point mutations into chromosomal bont/e gene of C. botulinum Beluga E. The resulting Beluga Ei strain displays unchanged physiology and produces inactive BoNT (BoNT/Ei) recognized in serological assays, but lacking biological activity detectable ex- and in vivo. Neither native single-chain, nor trypsinized di-chain form of BoNT/Ei show in vivo toxicity, even if isolated from Beluga Ei sub-cultured for 25 generations. Beluga Ei strain constitutes a safe alternative for the BoNT research necessary for public health risk management, the development of food preservation strategies, understanding toxinogenesis, and for structural BoNT studies. The example of Beluga Ei generation serves as template for future development of C. botulinum producing different inactive BoNT serotypes. [ABSTRACT FROM AUTHOR]

The review presents recent developments in the synthesis of polymeric photosensitizers and hybrid photocatalysts of various physicochemical and photochemical properties and their possible application for the degradation of water pollutants. The mechanisms of their action were presented. Photoactive amphiphilic polymers are selective and mild reagents acting as singlet oxygen generators or via photoinduced electron transfer. They can function independently as nano/micro heterogeneous photosensitizers or as components of the hybrid systems. The hybrid materials are usually dispersed in water and are involved in the generation of very reactive oxygen species, mostly superoxide and hydroxyl radical ions, which can oxidize organic compounds present in water. These systems are generally more photostable than photoactive polymers therefore they may function as photocatalysts. Polymeric and hybrid photocatalysts are especially well-suited for removal of chemical compounds which, although present at low concentrations in water resources, are dangerous due to their bioaccumulation in the food chain and often cannot be removed with the use of currently available technologies. Both photoactive polymeric and hybrid materials can be easily removed from the aqueous media thus the secondary contamination is avoided. [ABSTRACT FROM AUTHOR]

Abstract: The heterogeneous bis(cyclopentadienyl)zirconium(IV) dichloride catalyst of the composition MgCl2(THF)/(AlEt2Cl)0.34/(Cp2ZrCl2)0.01 as determined by FTIR, XRD, and AAS analyses was synthesised and, after activation by MAO, applied for ethylene polymerisation. The catalyst turned out to be stable and more active than those magnesium supported catalysts already known from the literature. The polyethylene produced has a relatively high molecular weight (M w >200,000g/mol), a narrow and monomodal molecular weight distribution (MWD=2.4), a bulk density of about 180g/dm3, and monomodal particle size distribution. Application of a ternary Al(i-Bu)3/MAO/B(C6F5)3 activator decreased the amount of MAO needed and increased catalyst activity, but did not change the reaction mechanism. [Copyright &y& Elsevier]

Abstract: The photosensitized oxidation of parathion-ethyl (PTE) pesticide in the aqueous solution of anthracene substituted dextran (DXA) was investigated. The phototransformation of PTE was found to be significantly enhanced in the presence of DXA. The suggested mechanisms of reactions involve photoinduced electron transfer process as a primary photophysical step. DXA polymer plays a role of environmentally friendly photosensitizer since after the reaction it undergoes decomposition. [Copyright &y& Elsevier]

This work describes the influence of the modification of the MgCl2(THF)2 and MgCl2 magnesium supports with the AlEt2Cl, MAO, AlEt3, AlMe3, and AlEt2Cl alkylaluminium compounds on heterogenisation of the bis(cyclopentadienyl) zirconium(IV) dichloride Cp2ZrCl2 catalyst. It was found that only the MgCl2(THF)2 support modified with AlEt2Cl gave the heterogeneous catalyst. On the contrary, application of a magnesium carrier modified by AlEt3, AlMe3, and MAO compounds only results in a homogeneous zirconocene catalyst. [Copyright &y& Elsevier]

The interactions of temperature-responsive copolymers of sodium 2-acrylamido-2-methyl-1-propanesulfonate (AMPS) and N-isopropylacrylamide (NIPAM) with a cationic surfactant, dodecyltrimethylammonium chloride (DTAC), have been studied. The content of AMPS in the copolymers ranged from 1.1 to 9.6 mol%. The surface activity was higher for the polymers with lower AMPS content. It was found that DTAC undergoes association with the polymer chain, forming mixed polymer–surfactant micelles. The values of cac for the polymers were found in fluorescence studies using pyrene as the fluorescent probe. They were in the range 0.9–3.6×10−3 M and were lower for polymers with higher AMPS content. An increase in DTAC concentration up to about its cmc results in a decrease of the LCST (lower critical solution temperature) of the copolymers, while further increase above the cmc results in an increase of the LCST. The minimum value of LCST in the presence of the surfactant is lower than the LCST of NIPAM homopolymer. [Copyright &y& Elsevier]

A series of novel terpolymers of sodium 2-acrylamido-2-methyl-1-propanesulfonate (AMPS), N-isopropylacrylamide (NIPAM) and cinnamoyloxyethylmethacrylate (CEMA) have been synthesized in a radical polymerization process using AIBN as an initiator in DMF at 60 °C. Five terpolymers were obtained by copolymerization of the monomer mixtures containing a fixed amount of 10 mol% of AMPS while the content of CEMA ranged from 5 to 25 mol% and was changed in 5 mol% increments. The terpolymers obtained are soluble in water. Due to their amphiphilic nature the terpolymers undergo self-organization in the aqueous solution with the formation of micelles. The terpolymers are sensitive to three stimuli, i.e. temperature, UV light and ionic strength. Terpolymers with small and medium content of CEMA formed both small (Rh=8–11 nm) and large (Rh=22–51 nm) micelles, while the terpolymer with the highest content of CEMA formed only large and relatively monodisperse micelles (Rh=28 nm), as found in the DLS measurements. The size of the micelles increases in response to both temperature and irradiation with UV light at λ=280 nm. The sensitivity to temperature is due to the presence of NIPAM which imposes the occurrence of lower critical solution temperature (LCST) while the sensitivity to UV light is due to the content of cinnamoyl chromophores which undergo photodimerization resulting in the photocrosslinking of the micelles. Irradiation of the micelles in aqueous solution of relatively high ionic strength results in the loss of their temperature-sensitivity. [Copyright &y& Elsevier]

The authors begin with a reflection upon the role of science in the life of modern society. Then, they cite and describe the science and technology (S&T) efforts and programmes of the European Union, particularly those directed towards the countries of Central and Eastern Europe, as well as programmes and activities targeted at developing co-operation between the countries of the region, including initiatives that are not those of the European Union. Finally, they conclude with a description of possible ways to enhance collaboration. [ABSTRACT FROM AUTHOR]

Examines the constraints in formalizing linguistic dialogue interaction. Linearity of logarithms of voice allocation in discussions; Interpretation of dialogues and verbal communication; Formal analogy between semantics and language.

Studies the photochemical step in the synthesis of vitamin D3 using solar light. Medium consisting of antenna polyelectrolyte poly(sodium styrenesulfonate-co-2-vinylnaphthalene); Application of photozymes as microphotoreactors; Use of solar energy to drive syntheses of organic compounds in water solution.

Studies the synthesis of a novel antenna cyclodextrin. Consideration of the ability of cyclodextrin to form inclusion complexes with a variety of guest molecules; Influence of cyclodextrin on the outcome of photochemical reactions; Selective formation of two possible coupling products.

The botulinum neurotoxin (BoNT) has been extensively researched over the years in regard to its structure, mode of action, and applications. Nevertheless, the biological roles of four proteins encoded from a number of BoNT gene clusters, i.e., OrfX1-3 and P47, are unknown. Here, we investigated the diversity of orfX-p47 gene clusters using in silico analytical tools. We show that the orfX-p47 cluster was not only present in the genomes of BoNT-producing bacteria but also in a substantially wider range of bacterial species across the bacterial phylogenetic tree. Remarkably, the orfX-p47 cluster was consistently located in proximity to genes coding for various toxins, suggesting that OrfX1-3 and P47 may have a conserved function related to toxinogenesis and/or pathogenesis, regardless of the toxin produced by the bacterium. Our work also led to the identification of a putative novel BoNT-like toxin gene cluster in a Bacillus isolate. This gene cluster shares striking similarities to the BoNT cluster, encoding a bont/ntnh-like gene and orfX-p47, but also differs from it markedly, displaying additional genes putatively encoding the components of a polymorphic ABC toxin complex. These findings provide novel insights into the biological roles of OrfX1, OrfX2, OrfX3, and P47 in toxinogenesis and pathogenesis of BoNT-producing and non-producing bacteria. [ABSTRACT FROM AUTHOR]

Human metapneumovirus (hMPV) is a widely distributed pathogen responsible for acute upper and lower respiratory infections of varying severity. Previously, we reported that N-sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) efficiently inhibit replication of the influenza virus in vitro and ex vivo. Here, we show a dose dependent inhibition of hMPV infection by NSPAHs in LLC-MK2 cells. The results showed strong antiviral properties of NSPAHs. While the activity of NSPAHs is comparable to those of carrageenans, they show better physicochemical properties and may be delivered at high concentrations. The functional assays showed that tested polymers block hMPV release from infected cells and, consequently, constrain virus spread. Moreover, further studies on viruses utilizing different egress mechanisms suggest that observed antiviral effect depend on selective inhibition of viruses budding from the cell surface. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxins (BoNTs) are among the most lethal toxins known to humans, comprising seven established serotypes termed BoNT/A–G encoded in two types of gene clusters (ha and orfX) in BoNT‐producing clostridia. The ha cluster encodes four non‐toxic neurotoxin‐associated proteins (NAPs) that assemble with BoNTs to protect and enhance their oral toxicity. However, the structure and function of the orfX‐type NAPs remain largely unknown. Here, we report the crystal structures for OrfX1, OrfX2, and an OrfX1–OrfX3 complex, which are encoded in the orfX cluster of a BoNT/E1‐producing Clostridium botulinum strain associated with human foodborne botulism. These structures lay the foundation for future studies on the potential roles of OrfX proteins in oral intoxication and pathogenesis of BoNTs. [ABSTRACT FROM AUTHOR]

A novel biopolymeric material in the form of nano/microspheres was developed which was capable of adsorbing coronaviruses. The biopolymer was obtained by crosslinking of chitosan (CHIT) with genipin, a nontoxic compound of plant origin, in inverted emulsion and reacting the chitosan nano/microspheres obtained (CHIT-NS/MS) with glycidyltrimethyl-ammonium chloride (GTMAC). As a result the nano/microspheres of N-(2-hydroxypropyl)-3-trimethyl chitosan (HTCC-NS/MS) were obtained. HTCC-NS/MS were studied as the adsorbents of human coronavirus NL63 (HCoV-NL63), mouse hepatitis virus (MHV), and human coronavirus HCoV-OC43 particles in aqueous virus suspensions. By studying cytopathic effect (CPE) caused by these viruses and performing PCR analyses it was found HTCC-NS/MS strongly adsorb the particles of HCoV-NL63 virus, moderately adsorb mouse hepatitis virus (MHV) particles, but do not adsorb HCoV-OC43 coronavirus. The adsorption capacity of HTCC-NS/MS well correlated with the antiviral activity of soluble HTCC against a given virus. Importantly, it was shown that HCoV-NL63 particles could be desorbed from the HTCC-NS/MS surface with a salt solution of high ionic strength with retention of virus virulence. The obtained material may be applied for the removal of coronaviruses, purification and concentration of virus samples obtained from biological matrices and for purification of water from pathogenic coronaviruses. [ABSTRACT FROM AUTHOR]

Perfluorophthalocyanines incorporating three-valent metals, namely In(Cl), Ga(Cl), and Al(Cl), have been synthesized and characterized. Thermogravimetric analysis revealed that these compounds exhibit outstanding thermal stability and a tendency to sublime at a temperature exceeding around 350 °C without thermal decomposition. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used to probe the frontier orbital energy levels of these compounds in THF solution. All three compounds undergo three quasi-reversible reductions with the first one leading to the formation of an anion radical, namely MPc−., as confirmed by spectroelectrochemistry. The compounds studied were intrinsically resistive to oxidation, which indicates that they are very good electron acceptors (n-type materials). The HOMO-LUMO energy gaps ( Eg) of the three compounds determined by UV/Vis spectroscopy were relatively unaffected by the three-valent metals incorporated into the phthalocyanine macrocycle. Similarly, the energies of the HOMO ( EHOMO) and LUMO ( ELUMO) orbitals remained virtually unaffected by the three-valent metals in the perfluorophthalocyanine. Importantly, all the perfluorophthalocyanines studied possess LUMO levels between −4.76 and −4.85 eV, which makes their reduced forms resistant to electron trapping by O2 and H2O. This property opens up the possibility for the fabrication of electronic devices operating under ambient conditions. All three compounds demonstrated very good photostability as solid thin films. [ABSTRACT FROM AUTHOR]

Modified adenosine nucleosides have been proposed to be potential DNA-based biomarkers for early diagnosis of tumor and a promising tool for the development of noninvasive prediction systems. However, the low concentration of modified adenosine nucleosides in physiological fluids makes them challenging for both quantitative and qualitative determination. Therefore, materials, which are potentially useful for selective adsorption of nucleobase-containing compounds, were obtained. To obtain the adsorbents, the silica gel particles were coated layer-by-layer with films of the polymers with different combinations of polymers containing thymine groups. Next, the microspheres were irradiated with UV light in the presence of 2'-deoxyadenosine or 5'-deoxy-5'-(methylthio)adenosine, as template molecules, which resulted in the photodimerization of thymine moieties and molecular imprinting of adsorbed modified adenosine compounds. The selectivity of the adsorption was significantly enhanced by the photoimprinting process. Eventually, the imprinted particles have shown an improved ability to recognize mainly 2'-deoxyadenosine and 5'-deoxy-5'-(methylthio)adenosine molecules. The best performing adsorbent was obtained using modified natural polysaccharides. The studied materials could serve as promising adsorbents of biomarkers for tumor diagnostics. [ABSTRACT FROM AUTHOR]

Highlights: [•] We examine the morphological changes of liposomes exposed to the serum environment. [•] Bare liposomes are disintegrated by serum as a result of high osmotic shock. [•] Polymer coating prevents the destruction of liposome vehicles by serum. [•] Polymer structure is crucial to the interactions of coated liposomes with serum. [•] Lipid membranes become more fluid after the addition of serum. [ABSTRACT FROM AUTHOR]

Abstract: Glucocorticoids (GCs) are broadly used in the treatment of inflammation and in suppressing hyperactivity of the immune system expressed in allergies, asthma, autoimmune diseases and sepsis. They are pleiotropic in nature, showing a wide range of diverse effects, including those which are harmful for the organism. Dexamethasone (DEX) is one of the most frequently used GCs and is considered as one of the safest. Still serious side-effects have been observed for this drug, mostly due to its hydrophobicity and low bioavailability. The potentially promising polymeric carrier systems to deliver DEX effectively are revised. [Copyright &y& Elsevier]

Abstract: The synthesis and spectroscopic characterization of the new phthalonitrile 5-tert-butyl-3-(trifluoromethyl)phthalonitrile is reported. A six-step route, which started with a regiospecific iodination, followed by CuI-catalyzed trifluoromethylation, is discussed. The title compound is also converted into the more reactive compound 6-tert-butyl-4-trifluoromethyl-1,3-diiminoisoindoline. [Copyright &y& Elsevier]

new bilayer-coated microbeads for oral delivery of 5-aminosalicylic acid (5-ASA) were prepared from naturally occurring polysaccharides via emulsification method. 5-ASA was successfully encapsulated in chitosan-λ-carrageenan-coated alginate microbeads. The morphology and sizes of microparticles were studied using optical microscopy and dynamic light scattering. Drug release profiles were followed using high-performance liquid chromatography (HPLC) with spectrophotometric detection. The effect of chitosan thin layer and chitosan-λ-carrageenan bilayer on the drug release was studied at pH values simulating these characteristic for stomach (pH = 1.2) and intestine (pH = 7.4). Chitosan layer slightly increased 5-ASA release at pH = 1.2, whereas double-layer external coating decreased the release rates. Due to the bilayer properties, the micro-carriers were additionally protected against acidic conditions of the stomach and drug release in the intestine could be better controlled. [ABSTRACT FROM AUTHOR]

Abstract: A new type of hybrid photosensitizers was obtained by efficient adsorption of a photoactive polymer by an organically modified nanoclay. The polymer bore naphthyl and rose bengal chromophores, which absorbed light both in the ultraviolet and visible spectral region. Adsorption of the polymer on nanoclay prevented aggregation of chromophores. The obtained hybrid photosensitizer efficiently adsorbs hydrophobic compounds. It was also found to be an efficient photosensitizer in singlet oxygen generation. The hybrid photosensitizers combine the advantages of both component systems, i.e. possibility to attach a wide range of chromophores to the polymeric chain and resulting ability to photosensitize reactions, on one hand, and the ability to adsorb hydrophobic pollutants and easy separation from water characteristic of nanoclays, on the other. [ABSTRACT FROM AUTHOR]

Abstract: Photooxidation of phenol sensitized by Aldrich humic acid (AHA) has been studied in an aqueous solution at neutral and basic pH. Solutions containing phenol and AHA of various concentrations were irradiated with monochromatic light at 253.7nm or with polychromatic light within the wavelength range of 310–420nm. The quantum yields of phenol photodegradation under these conditions were determined. At the wavelength of 253.7nm direct degradation of phenol was much more effective than that sensitized by AHA. With polychromatic light the photooxidation was found to be strongly dependent on pH of aqueous solution and independent on AHA concentration. [Copyright &y& Elsevier]

• The biological in vitro studies of silicone-stabilized liposomes are presented. • Biocompatibility of developed stabilized liposomes was demonstrated. • AFM investigation revealed better elastomechanical features of resulted liposomes. • Silicone layer brought substantial increase in elastic modulus of obtained liposomes. • Developed silicone-stabilized liposomes are promising candidates for drug nanocariers. The liposomes are among the most promising types of drug delivery systems but low stability significantly limits their application. Some approaches proposed to overcome this drawback may affect the liposomes toxicity profile. It is assumed that developed by us and presented here stabilization method involving formation of silicone network within the liposomal bilayer will improve elastomechanical properties of vesicles while not deteriorating their biocompatibility. The silicone-stabilized liposomes were prepared by base-catalyzed polycondensation process of the 1,3,5,7-tetramethylcyclotetrasiloxane (D 4 H) within the liposomal bilayer. The systematic biological in vitro studies of vesicles obtained were carried out. Moreover, the elastomechanical features investigation employing atomic force microscopy (AFM) measurements was performed. These properties of the liposome membrane are of great importance since they define the nanocarriers' stability as well as play a significant role in their cellular uptake via endocytosis. Applying the Derjaguin–Muller–Toporov (DMT) model, the elastic modulus of the silicone-stabilized liposomes was determined and compared to that characteristic for the pristine liposomes. The in vitro biological evaluation of silicone-stabilized liposomes demonstrated that these vesicles are not toxic for blood cells isolated from healthy donors and they do not induce oxidative stress in HepG2 cells. AFM results confirmed the stabilizing effect of silicone and revealed that the silicone network improves the elastomechanical properties of the resulted liposomes. This is the first report demonstrating that the silicone-stabilized liposomes retain biocompatibility of pristine liposomes' while acquire significantly better elastomechanical features. [ABSTRACT FROM AUTHOR]

Abstract: An improved six-step synthesis of 5-tert-butyl-3-nitrophthalonitrile (1) is described. The title compound and all the intermediates are fully characterized spectroscopically (FT–IR, 1H NMR, 13C NMR, MS). In addition, single-crystal X-ray diffraction further confirmed the structure of the title compound. [Copyright &y& Elsevier]

Novel, biocompatible, multifunctional, injectable genipin crosslinked collagen/chitosan/lysine-modified hyaluronic acid based hydrogels (ColChHA mod) were prepared in a facile, one-step procedure. The novelty of the current approach lies in the functionalization of hyaluronic acid (HA) with primary amine groups by lysine attachment, and its further use as a component of the injectable sol. The obtained derivative, HA mod , could form, upon crosslinking with genipin, covalent bonds with other components of the hydrogel network, resulting in structurally stable, better-defined hydrogels. We have demonstrated that, by adjusting HA mod content and genipin concentration, hydrogels with tunable physicochemical characteristics (swelling, wettability, tendency for enzymatic degradation) and properties adequate for the potential bone tissue regeneration can be prepared. Storage modulus measurements indicated that HA mod has positive effect on mechanical characteristics of hydrogels prepared. It was also revealed that the ColChHA mod -based hydrogels are characterized by a high porosity (85–95%). The in situ rheological measurements confirmed the injectability of the obtained hydrogels. The in vitro cell culture studies showed that the surface of all materials prepared was biocompatible, as they supported proliferation and adhesion of osteoblast-like cells followed by ALP expression. The intrinsic antibacterial activity of the hydrogels against Escherichia coli was also demonstrated in in vitro experiment. Unlabelled Image • Novel collagen/chitosan/modified hyaluronic acid based hydrogels were obtained. • Hyaluronic acid was functionalized with amine groups by reacting it with lysine. • Physicochemical features of the developed injectable hydrogels are tunable. • Biocompatibility and antibacterial activity of resulting materials was confirmed. • Hydrogels exhibit promising properties as a potential multifunctional scaffolds. [ABSTRACT FROM AUTHOR]

Synthesis of tetraphenyl‐pyrrole‐2‐yl squaraines is introduced for the first time. An improved, reproducible and straightforward method for the preparation of 2,4‐diphenylpyrrole‐a key structural synthon for the preparation of the squaraines in question‐is reported. Both, squaraine dyes and all intermediates were fully characterized using spectroscopic methods, viz. 1H NMR, 13C NMR, 2D NMR (COSY, HSQC, HMBC), FT‐ATR‐IR, ESI‐HRMS. The structures of tetraphenyl‐pyrrol‐2‐yl squaraines were unambiguously confirmed by single X‐ray analysis. The squaraines studied exhibit an intense absorption bands spanning from ca. 600 to 700 nm, entering to the spectral region, which is highly sought after for biomedical applications and advanced material technologies. [ABSTRACT FROM AUTHOR]

Phenomena that occur between an insulin and four different positively charged polymers (protamine, cationic dextran, chitosan, and poliallylamine derivatives) were studied by dynamic light scattering and fluorescence measurements (using fluorescein-labeled polymers). These processes were compared to the reaction of polycations with heparin that is responsible for the neutralization of anticoagulant activity in blood stream.The nature of polycations interaction with heparin is electrostatic, while the interaction with insulin is more complicated.We observed that the presence of zinc atoms (and its complexing by nitrogen from macromolecules) is critical for insulin suspensions formation and stability. The differences between the nature of these two reactions were revealed. The highly immunogenic action of protamine present in long-acting insulin products makes it reasonable to develop similar systems based on the nonprotein polycations. [ABSTRACT FROM AUTHOR]

Collagen, chitosan and hyaluronic acid based multicomponent injectable and in situ gellating biomimetic hybrid materials for bone tissue engineering applications were prepared in one-step procedure. The bioactive phase in the form of surface-modified silica particles was introduced to the solutions of biopolymers and simultaneously crosslinked with genipin both the biopolymer matrix and dispersed particles at 37 °C. The novel approach presented here involved the use of silica particles which surfaces were priory functionalized with amino groups. That modification makes possible the covalent attachment of silica particles to the polymeric hydrogel network on crosslinking with genipin. That methodology is especially important as it makes possible to obtain the hybrid materials (biopolymer-silica particles) in which the problems related to the potential phase separation of mineral particles, hindering their in vivo application can be eliminated. The hybrids of various compositions were obtained and their physicochemical and biological properties were determined. The in vitro experiments performed under simulated body fluid conditions revealed that the amino-functionalized silica particles covalently attached to the biopolymeric network are still bioactive. Finally, the in vitro cell culture studies shown that the materials developed are biocompatible as they supported MG-63 cells adhesion, proliferation as well as Alkaline phosphatase (ALP) expression. Unlabelled Image [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract A cationic derivative of γ-cyclodextrin (GCD) modified with propylenediamine (PDA) was synthesized. It was shown that the derivative (GCD–PDA) is mucoadhesive and resistant to the digestion with ∝-amylase indicating that it may constitute an efficient oral delivery vehicle. GCD-PDA formed an inclusion complex with berberine (BBR), an alkaloid displaying a multitude of beneficial physiological effects. The complexed BBR penetrates a lipid membrane easier than the free one. Both uncomplexed BBR and that complexed with GCD-PDA was delivered to normal (NMuMG) and cancerous (4T1) murine mammary gland cells. In the normal cells both free and complexed BBR was homogeneously dispersed in the cytoplasm and was nontoxic up to 131 μM. In the cancerous cells uncomplexed BBR was also homogeneously dispersed but it was toxic to about 25% of cells at 131 μM, while the GCD-PDA/BBR complex was preferably localized in lysosomes and its toxicity doubled at this concentration compared to that of free BBR. Moreover, free BBR and GCD-PDA/BBR showed even more efficient inhibitory effect against murine melanoma (B16-F10) cells than against 4T1 cells. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Conjugate of sodium alginate and curcumin was synthesized in easy one-step process. • Conjugate forms micelles already at the concentration slightly above 0.2 mg/ml. • Prolonged release of curcumin was achieved for physically cross-linked micelles. • Conjugate did not induce red cells aggregation, hemolysis or significant toxicity. • Dose dependent sensitivity of tested cancer cells to the conjugate was observed. Abstract The bioconjugate of alginate and curcumin (AA-CUR) was synthesized in a simple, one-step process and used to prepare the stable calcium cross-linked spherical micelles serving as a delivery vehicle for curcumin. Above its critical micelle concentration (0.6 mg/ml) AA-CUR forms colloidally stable micelles of ca. 200 nm. Prolonged, well controlled release of curcumin was observed from the AA-CUR micelles cross-linked with calcium ions for 5 h under the physiological conditions. To assess the safety of applying the bioconjugate into the bloodstream for possible anti-cancer applications, the interaction between AA-CUR and cells isolated from human blood was analyzed. No red cells aggregation or hemolysis was observed. AA-CUR was also shown to have no significant cytotoxicity to the human Peripheral Blood Mononuclear Cells (PBMC) isolated from peripheral blood of healthy donors and to the mouse primary brain endothelial cells. To evaluate the efficiency of the obtained bioconjugate in the anti-cancer therapy, the micellar solution of AA-CUR was tested against various cancer cells lines: mammary carcinoma 4T1, melanoma B16F10 and colon carcinoma CT26-CEA and MC38-CEA. The bioconjugate at the concentration of 0.7 mg/ml decreased the viability of cancer cells by ca. 80%. The cellular uptake of AA-CUR was rapid and the highest micelles accumulation was detected within 1 h after treatment. The AA-CUR micellar system can serve as an effective and safe delivery vehicle for curcumin. [ABSTRACT FROM AUTHOR]

Abstract Lactobacillus rhamnosus GG is an environmentally and human-friendly bacteria that can be found in probiotics. However, it is incapable of forming a biofilm on metal surfaces, what limits the possibility of using it in bioelectrochemical systems (BESs) as promising and green alternatives. Hence, we propose a simple and cost-effective modification of metal surface with cationic dextran derivative (DEX-G) by using the electrostatically driven self-assembly procedure resulting in the formation of a polymeric monolayer. Modification of metal electrodes was confirmed by using infrared spectroscopy (IR) and atomic force microscopy (AFM). Synthesized metal/polycation electrodes provided a bioactive environment for L. rhamnosus GG enhancing its proliferation and formation of the biofilm as confirmed by SEM imaging. Moreover, using cyclic voltammetry (CV) and chronoamperometry measurements, it was proven that metal/polycation/ L. rhamnosus bioelectrodes are electrochemically active in the glucose-rich medium. The electrochemical activity of fabricated bioanodes allows to consider them for their potential use in the bioelectrochemical systems. Graphical abstract Image 1 Highlights • Metal surface modification method facilitating the biofilm formation is proposed. • Use of lactic acid bacteria for bioelectrochemical systems is examined. • Cationic dextran coating enhanced bacteria colonization of gold. • The electroactivity of proposed bioanodes was confirmed by cyclic voltammetry. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Alkaline phosphatase was successfully incorporated into the halloysite nanoclay. • The halloysite-bound enzyme exhibits increased thermal stability. • The activity of the encapsulated enzyme was pH-independent in a wide range of pH (3–10). • Alkaline phosphatase-halloysite nanocomposite effectively promoted biomineralization. • The proposed nanocomposite may constitute an attractive biocomponent of bone scaffolds. Abstract Alkaline phosphatase (ALP) was sucessfully incorporated into the halloysite (HAL) nanotubes, as confirmed by FTIR-ATR and XRD analyses. The loading efficiency (LE) of ALP was found to be 13.5%, while its encapsulation efficiency (EE) was estimated to be around 27%, as determined using the Bradford test. The influence of the immobilization in HAL on the enzyme activity was measured using standard ALP activity assay. Immobilized ALP effectively induced the bomineralization process, as showed by SEM, EDS, and XRD studies. As a result, calcium phosphate was produced in the form of hydroxyapatite cauliflower-like structures, with a slight content of calcium hydroxide. Interestingly, the encapsulation of ALP guest molecules in the HAL nanotubes considerably increased its thermal stability, most probably due to the heat sink effect. The activity of HAL-bound ALP was also found to be pH-independent in the wide range of pH values (3–10) due to the amphoteric nature of the aluminum oxide lining the HAL nanotube internal surface. Due to an increased resistance to the unfavorable conditions, which are often encountered during scaffold preparation or sterilization, ALP-HAL nanocomposite material may constitute an attractive bioactive component of the scaffolds for bone regeneration. [ABSTRACT FROM AUTHOR]

The interaction between oppositely charged membranes and polycations causes cell aggregation, loss of membrane fluidity, and membrane degeneration and may cause an increase of its permeability. Unfortunately, the interaction is the reason why the use of polycations in medicine is severely limited. Therefore, in this paper, we share our observations related to the action of 40-kDa dextran modified using glycidyltrimethylammonium chloride, resulting in increased fibroblast cell proliferation. Using viability and proliferation tests [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, crystal violet, 3H-thymidine incorporation], we have observed that cationic dextran derivatives exert a positive impact on nonepithelial cell proliferation in vitro. This phenomenon has been noted for human and mouse fibroblasts and several other nonepithelial cell lines. However, the effect seems to be most pronounced for fibroblast cell lines. The presented studies allow to examine the impact of the polymer structure and the methods of its cationic modification on this newly observed phenomenon. The observation is unique because positively charged macromolecules usually exhibit high toxicity in all cell types in vitro. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Novel bionanocellulose blend with covalently bounded silicone layer was developed. • Silicone modified blend exhibits lower tendency to swell compared to pure material. • Developed silicone layers extended the drying time of bionanocellulose membranes. • The silicone covered membranes are promising materials for new wound dressing. Abstract Modification of membrane surface fabricated from bionanocellulose (BNC) carboxymethylcellulose (CMC) blend (BNC-CMC) with covalently bounded silicone layer was carried out in view of developing the novel, moist wound dressing material. The procedure was initiated with the reaction of aminopropyltriethoxysilane (APS) with carboxymethyl groups of CMC resulting with amide bound formation. The thickness of the silicone layer was further increased in the base-catalyzed polycondensation of silicone precursors: vinyltriethoxysilane (VES) or allyltrimethoxysilane (ATMS) initiated by N -(3-dimethylaminopropyl)- N ′-ethylcarbodiimide hydrochloride (EDC). Surface modification was confirmed using various physicochemical methods such as FTIR, SEM, XPS and contact angle measurements. Swelling and drying tests confirmed that silicone-modified materials have considerable better water storage properties than the pristine BNC-CMC nanocomposite. The fabricated silicone modified BNC-CMC membranes are promising materials for wound dressing ensuring improved hydrobalance as the protective layer slows the evaporation of water. [ABSTRACT FROM AUTHOR]

In view of the ever‐growing demand for efficient triplet photosensitizers and photoactive components of various optoelectronic devices, we herein report the synthesis and properties of hexaiodo‐subphthalocyanines (I6SubPcs). The improved five‐step route to 4,5‐diiodophthalonitrile, which serves as precursor for the synthesis of the I6SubPcs, is reported. The improved synthesis merely required one chromatographic separation to afford the high‐purity target product. Highly desirable photophysical and photochemical properties were induced in the I6SubPcs due to the presence of six heavy iodine atoms. In particular, high values of the singlet‐oxygen quantum yields (ΦΔ) ranging from 0.83 to 0.9 were measured. The I6SubPcs investigated proved to be phosphorescent at 77 K in 2‐MeTHF with emission band maxima (λP) located at λ=957 and 970 nm. The excited‐triplet‐state energies (ET) were estimated to be approximately 1.30 eV, whereas the triplet lifetimes (τT) were found to be 27.7 and 30.1 μs. The CV/DPV measurements indicated that both I6SubPcs exhibited one irreversible oxidation and one quasi‐reversible reduction. The spectroelectrochemical measurements pointed to a relative stability and reversibility of the electrochemically formed anion radical, that is, I6SubPc.−, and an instability of the species formed upon one‐electron oxidation, that is, I6SubPc.+. Estimation of EHOMO gave a value of approximately −5.8 eV whereas ELUMO was found to be located at around −3.8 eV. Heavy atoms: Highly desirable photophysical/photochemical properties were induced in subphthalocyanine by iodination of the peripheral aromatic rings. In particular, exceptionally high singlet oxygen quantum yields were obtained for this compound which place this subphthalocyanine among the best photosensitizers described thus far and recommend it as photocatalysts and photosensitizers for biomedical applications. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Biopolymeric chemically crosslinked hydrogels were obtained and characterized. • Hydrogels’ properties can be tuned by changing hyaluronic acid and genipin content. • The in vitro cell culture study show that the hydrogels’ surfaces are biocompatible. • Obtained hydrogels can serve as a novel promising biomimetic injectable scaffolds. Abstract Studies on synthesis, physico-chemical and biological properties of novel biomimetic materials, potentially useful as injectable hydrogels are presented. These materials are in situ prepared chemically crosslinked collagen/chitosan/hyaluronic acid-based hydrogels exhibiting potential for tissue regeneration. Optimization of hydrogels involved testing the effect of various concentration of crosslinking agent (genipin) as well as different ratios of biopolymers used on their properties. The changes in the content of hyaluronic acid and in the genipin concentration used have been shown to be crucial. Employing the highest concentration of crosslinking agent studied (20 mM) the hydrogels of compact structure, characterized by good mechanical properties and prolonged degradation profile can be obtained. Changing the HA content in sol mixture the hydrogel of various wettability; more or less hydrophilic when compared to pure collagen/chitosan hydrogels can be fabricated. The in vitro cell culture study has shown that the surface of the prepared materials ensures suitable biocompatibility. These hydrogels can support the proliferation and adhesion of MG-63 cell line as it was demonstrated using Alamar Blue assay and SEM observations. It is believed that the collagen/chitosan/hyaluronic acid hydrogels crosslinked with genipin are particularly promising materials for bone regeneration procedures, especially attractive for regeneration of small bone losses. This is the first paper in the litearature presenting results of studies on that type of biopolymeric injectable hydrogels chemically crosslinked with genipin. [ABSTRACT FROM AUTHOR]

When designing materials for tissue engineering applications various parameters characterizing both materials and tissue have to be taken into account. The characteristics such as chemistry, elasticity, wettability, roughness and morphology of the substrate’s surface have significant impact on cell behavior. The paper presents biopolymer (collagen/chitosan) based hydrogel materials with tunable elasticity and surface properties useful for fabrication of substrates for cell culture. Using simple chemical approach involving the change in concentration of crosslinking agent (genipin) and composition of the reaction mixture the hydrogels characterized with various features were obtained. Detailed analysis of morphology, topography, roughness and elasticity of surface performed using Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM) and rheological measurements has shown that the topographical aspects and roughness parameter can be modulated in nanoscale regime (13–47 nm). Substrate’s elasticity could be modified in a wide range (0.2–270 kPa). Biological in vitro studies on fibroblasts behavior revealed that the materials prepared provide satisfactory conditions for cell culture, ensuring their high viability, good adhesion and normal morphology. The genipin crosslinked collagen-chitosan hydrogels characterized by denser fiber structure, higher elasticity and lower surface roughness are the most attractive supports for fibroblasts cultivation. The results obtained indicate that the properties of the materials developed can be easily tailored to the needs of the given type of cells. [ABSTRACT FROM AUTHOR]

Herpes simplex virus type 1 (HSV-1) is a widespread human pathogen known to cause infections of diverse severity, ranging from mild ulceration of mucosal and dermal tissues to life-threatening viral encephalitis. In most cases, standard treatment with acyclovir is sufficient to manage the disease progression. However, the emergence of ACV-resistant strains drives the need for new therapeutics and molecular targets. HSV-1 VP24 is a protease indispensable for the assembly of mature virions and, as such, constitutes an interesting target for the therapy. In this study, we present novel compounds, KI207M and EWDI/39/55BF, that block the activity of VP24 protease and consequently inhibit HSV-1 infection in vitro and in vivo. The inhibitors were shown to prevent the egress of viral capsids from the cell nucleus and suppress the cell-to-cell spread of the infection. They were also proven effective against ACV-resistant HSV-1 strains. Considering their low toxicity and high antiviral potency, the novel VP24 inhibitors could provide an alternative for treating ACV-resistant infections or a drug to be used in combined, highly effective therapy. [Display omitted] • A library of compounds was designed to target HSV-1 capsid protease. • Two compounds inhibited the protease, hindering virus replication. • VP24 protease inhibitors block viral capsid egress from the cell nucleus. • The compounds were effective against acyclovir-resistant HSV-1. • Protease inhibitors protected mice from lethal HSV-1 challenge. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess osteogenic potential of three groups of biopolymeric hydrogel-based surfaces made of plain collagen, chitosan or collagen/chitosan, crosslinked with genipin or all three biopolymers modified with silica particles of two sizes (S1 = 240 nm and S2 = 450 nm). Biocompatibility and osteoinductive properties of the resulting composites were analyzed in the human bone marrow-derived mesenchymal stromal cells (hBMSCs) in vitro cultures. It was revealed that all tested materials are biocompatible and significantly enhance ALP activity in hBMSCs which was particularly pronounced for collagen/chitosan based hybrids. Gene expression ( RUNX-2 , COL-I , OC and VEGF mRNA) analyses performed in hBMSCs cultured at collagen/chitosan materials showed that ColChS1 hybrid the most effectively promotes osteogenic differentiation of hBMSCs. SEM and EDS analyses of materials carried out after 20 days of hBMSCs culturing on ColCh-based hydrogels revealed that the hybrid materials enhanced hBMSCs-mediated mineralization of ECM. Our studies revealed that collagen/chitosan hydrogels modified with silica particles of smaller sizes (ColChS1) exhibit high pro-osteogenic properties without the need of applying any additional osteogenic inducers. That suggests that ColChS1 having the intrinsic osteoinductive activity holds great potential as material of choice for bone regeneration procedures, especially in regeneration of small bone losses. [ABSTRACT FROM AUTHOR]

Silicone micromaterials were synthesized using two surfactant-free methods: the Stöber synthesis or solidification in spontaneously formed emulsions (the Ouzo effect) and their physicochemical properties were evaluated. The effect of the chemical structure of a silicone precursor on the morphology of formed microstructures was considered. For that purpose, various organosilicon compounds containing in their structure T-units and D-units, methyl groups, ethylene linkages, and cyclotetrasiloxane rings were used as silicone precursors. All materials existed as sub-micron sized particles, although they differed considerably in morphology and dispersity (spherical particles with a diameter of about 490 and 740 nm, cauliflower-like structures, large rough-surfaced aggregates). The chemical composition of the microstructure surface was examined using XPS. The porosity of silicone materials was assessed on the basis of nitrogen adsorption isotherms. The specific surface area (S BET ) varied substantially and ranged from 5 to 379 m 2 /g. For the first time the microelastic modulus of the silicone materials was determined using AFM measurements. We found that the structure of the organic part had a large impact on the microelasticity of the material. The microelastic modulus of the silicone materials (11–33 GPa) was significantly lower compared to silica (59 GPa). [ABSTRACT FROM AUTHOR]

Phthalocyanines are promising photosensitizers for photodynamic therapy (PDT). A novel zinc 1,8(11),15(18),22(25)-tetraiodo-3,10(9),17(16),24(23)-tetra- tert -butylphthalocyanine has been synthesized and characterized. The synthesis of iodinated phthalocyanine was achieved through templated cyclotetramerization of 6- tert -butyl-4-iodo-1,3-diiminoisoindoline around zinc ions (Zn 2+ ). A six step route leading to 6- tert -butyl-4-iodo-1,3-diiminoisoindoline was proposed. The synthesis started with a regiospecific iodination of 4- tert -butyl- o -xylene to 5- tert -butyl-2,3-dimethyl-iodobenzene, followed by oxidation of the methyl groups to phthalic acid, conversion of phthalic acid to phthalimide, hydrolysis of phthalimide to phthalamide, conversion of phthalamide to phthalonitrile, followed by conversion of phthalonitrile to a more reactive 6- tert -butyl-4-iodo-1,3-diiminoisoindoline. Highly desirable photophysical and photochemical properties were induced in zinc phthalocyanine by iodination of the aromatic rings, while the presence of tert -butyl groups rendered the compound non-aggregating in solution. The photosensitizer studied exhibits absorption band within the so-called “therapeutic window”, with λ max at 689 nm and very high molar absorption coefficient of 295 000 [M −1  cm −1 ] in DMF. Transient absorption experiment revealed T 1  → T n absorption spanning from ca. 400 nm to ca. 600 nm and allowed determination of the excited triplet state lifetime ( τ T ). The estimated τ T in THF equaled 3.3 μs. The phosphorescence maximum was found to be located at λ P 1103 nm and the excited triplet state energy ( E T ) equaled 1.12 eV in 2-methyltetrahydrofuran at 77 K. The photosensitizer studied is characterized by a high value of singlet oxygen quantum yield (Φ Δ ) of ca. 0.76 and the photooxygenation process proceeds via Type II mechanism under the experimental conditions applied. The photodegradation studies revealed that the iodinated phthalocyanine was moderately stable in the presence of oxygen with quantum yield of photodegradation (Φ d ) equaled 4.01 × 10 −4 . Moderate photostability of photosensitizer is advantageous from a PDT point of view where rapid breakdown and fast clearance from the patient’s system is necessary to avoid prolonged skin photosensitivity following treatment. [ABSTRACT FROM AUTHOR]

Fluorescence resonance energy transfer (FRET) system based on functionalized CdTe-guanine and AuNPs-cytosine bioconjugates for the model nucleobase - guanine detection was developed. Thioglycolic acid coated cadmium telluride quantum dots (QDs) conjugated with guanine and sodium 3-mercapto-1-propanesulfonate stabilized gold nanoparticles (AuNPs) capped by cytosine were obtained and fully characterized. Successful formation of the materials was confirmed by UV–Vis, fluorescence and FTIR spectroscopies. Composition of the conjugates was also characterized with elemental analysis and XPS. By employing a guanine-cytosine interaction the bonding between these complementary nucleobases attached to the nanoparticles leads to the formation of QDs-guanine-AuNPs-cytosine assembly, with the size about 7 nm as demonstrated using atomic force microscopy. That enables an effective FRET from functionalized QDs to AuNPs since both, the required distance and the spectral characteristics of donor-acceptor pair were secured. However, it was shown that in the presence of guanine-model molecule which inhibits the interaction between conjugated QDs and AuNPs the FRET is efficiently hampered. Thus monitoring the changes in the restoring fluorescence signal allows to assay the free guanine concentration. Importantly, we have demonstrated the sensitivity and selectivity of the obtained FRET-based system towards guanine. Moreover, in order to confirm the feasibility of the proposed material for nucleobase detection in the real biological samples the developed nanoparticles were also evaluated under simulated urine conditions. The presented strategy of FRET-based conjugated system preparation might be easily used for the development of another nucleobases selective detection and thus opens many possibilities for the determination of biomolecules in the real samples. [ABSTRACT FROM AUTHOR]

A series of novel iodinated NO2-substituted aza-BODIPYs have been synthesized and characterized. Highly desirable photophysical and photochemical properties were induced in NO2-substituted aza-BODIPYs by iodination of the pyrrole rings. In particular, high values of singlet oxygen quantum yields ( ΦΔ) ranging from 0.79 to 0.85 were measured. The photooxygenation process proceeds via a Type II mechanism under the experimental conditions applied. The compounds studied exhibited an absorption band within the so-called 'therapeutic window', with λmax located between 645 nm to 672 nm. They were non-fluorescent at room temperature with excited singlet-state lifetimes within the picosecond range as measured by femtosecond transient absorption. Nanosecond laser flash photolysis experiments revealed T1→T n absorption spanning from ca. 400 nm to ca. 500 nm and allowed determination of the triplet-state lifetimes. The estimated triplet lifetimes ( τT) in deaerated acetonitrile ranged between 2.74 μs and 3.50 μs. As estimated by CV/DPV measurements, all iodinated aza-BODIPYs studied exhibited one irreversible oxidation and two quasi-reversible reductions processes. Estimation of the EHOMO gave the value of −6.06 to −6.26 eV while the ELUMO was found to be located at ca. −4.6 eV. Thermogravimetric (TGA) analysis revealed that iodinated aza-BODIPYs were stable up to approximately 300 °C. All compounds studied exhibit high photostability in toluene solution. [ABSTRACT FROM AUTHOR]

Novel system based on bionanocellulose modified with carboxymethyl groups (mBNC) and covalently attached hydrogel submicron particles with encapsulated curcumin was prepared and its usefulness for the preparation of bioactive wound dressing materials was demonstrated. In order to obtain a well-controlled delivery system, curcumin was first encapsulated in Pluronic ® P103 micelles and subsequently entrapped in the particles prepared by the extrusion method using commercially available, relatively inexpensive and biocompatible polymers: sodium alginate (ALG) and hydroxypropyl cellulose (HPC). The size of the particles and the feed ratio of curcumin and ALG were optimized during the synthesis in respect with the curcumin loading and release profile. The particles were coated with chitosan and successfully immobilized on the surface of mBNC using EDC/NHC chemistry. The particles attached to the mBNC surface released the curcumin in a sustain, well controlled manner, resembling that of the unbounded particles. Their presence allows for prolonged bioactivity of the potential wound dressing material. [ABSTRACT FROM AUTHOR]

Human herpesviruses are among the most prevalent pathogens and currently there are no drugs available that could cure diseases induced by them. The most widely utilized antiherpes drugs, acyclovir and its derivatives, have serious limitations, such as low bioavailability and severe side effects. The current paper reports on the synthesis and characterization of cationic dextran derivatives (DEXxDSy) of various molecular weights and various degrees of substitution with ammonium groups, which were tested as antiherpes agents. DEXxDSy showed high effectiveness against HSV-1 and HSV-2 viruses, as found using a variety of techniques. Importantly, no toxicity was observed for these compounds in the range of active concentrations, demonstrating their potential as antivirals. The mechanism of action of DEXxDSy was assessed. We hypothesize that they may limit virus transmission, as extensive examination showed that they hamper the interaction between the virus and the cellular attachment receptor. [ABSTRACT FROM AUTHOR]

The optical and electrochemical properties are compared for aza-BODIPY dyes that differ by virtue of the substituents at 1,7- and 3,5-positions of the aza-BODIPY backbone. In particular, the impact of highly electron-withdrawing nitro substituents on these properties is of consideration. The aza-BODIPYs studied exhibit a broad absorption band spanning from ca. 600 nm to ca. 700 nm – a spectral region that is highly sought after for biomedical applications – and possess high molar absorption coefficients (ε) ranging from 64 000 [M−1 cm−1] to 85 000 [M−1 cm−1] in THF. The compounds studied are weakly emissive as non-radiative decay is the predominant way of the excited state energy dissipation. Exemplarily, the fluorescence quantum yields (Φfl) measured in THF were in the range of 0.03 to 0.06 for the aza-BODIPYs studied. Transient absorption experiments revealed T1→ Tn absorption spanning from ca. 400 nm to ca. 600 nm and allowed determination of the triplet state lifetimes. The estimated triplet lifetimes (τT) in deaerated THF ranged from 77 µs to 130 µs. As estimated by the CV/DPV measurements, all aza-BODIPYs studied exhibited one irreversible oxidation and two quasi-reversible reductions. Estimation of the EHOMO gave a value of ca.−5.8 eV while the ELUMO was found to be located at ca.−4.5 eV. Extremely high photostability and thermal robustness up to approximately 300 °C were found for the nitro-substituted aza-BODIPYs. [ABSTRACT FROM AUTHOR]

Polymersomes and complex coacervates have been the subject of considerable interest due to their wide application as compartments for the encapsulation of various actives. In this paper, we present for the first time that the transformation of small unilamellar vesicles (polymersomes) to coacervate microdroplets is possible by a simple adjustment of the ionic strength. We demonstrated that a pair of zwitterionic-ionic copolymers self-assembles in an aqueous medium forming small unilamellar polymersomes. Cryo-transmission electron microscopy showed that the polymersomes had a diameter of 120 ± 49 nm and a membrane thickness of 25–30 nm. The polymersomes are stable at low ionic strength including physiological conditions, but they can be transformed into the coacervate microdroplets of several µm in diameter by increasing the salt concentration. The process can be reversed by reducing the salt concentration, what leads to the spontaneous formation of giant or small polymersomes. These studies contribute to the development of polymeric materials that can self-organize into ionic strength- responsive vesicular and solid structures (without the use of organic solvents) potentially useful for compartmentalization. [ABSTRACT FROM AUTHOR]

Interaction of polycations with lipid membranes is a very important issue in many biological and medical applications such as gene delivery or antibacterial usage. In this work, we address the influence of hydrophobic substitution of strong polycations containing quaternary ammonium groups on the polymer-zwitterionic membrane interactions. In particular, we focus on the polymer tendency to adsorb on or/and incorporate into the membrane. We used complementary experimental and computational methods to enhance our understanding of the mechanism of the polycation-membrane interactions. Polycation adsorption on liposomes was assessed using dynamic light scattering (DLS) and zeta potential measurements. The ability of the polymers to form hydrophilic pores in the membrane was evaluated using a calcein-release method. The polymer-membrane interaction at the molecular scale was explored by performing atomistic molecular dynamics (MD) simulations. Our results show that the length of the alkyl side groups plays an essential role in the polycation adhesion on the zwitterionic surface, while the degree of substitution affects the polycation ability to incorporate into the membrane. Both the experimental and computational results show that the membrane permeability can be dramatically affected by the amount of alkyl side groups attached to the polycation main chain. [ABSTRACT FROM AUTHOR]

Uptake of piroxicam, a non-steroidal anti-inflammatory drug, from the intestines after oral intake is limited due to its low solubility and its wide use is associated with several side effects related to the gastrointestinal tract. In this study, all-atom molecular dynamics (MD) simulations and fluorescent spectroscopy were employed to investigate the interaction of piroxicam in neutral, zwitterionic, and cationic forms with lipid bilayers composed of phosphatidylcholine, cholesterol, and PEGylated lipids. Our study was aimed to assess the potential for encapsulation of piroxicam in liposomal carriers and to shed more light on the process of gastrointestinal tract injury by the drug. Through both the MD simulations and laser scanning confocal microscopy, we have demonstrated that all forms of piroxicam can associate with the lipid bilayers and locate close to the water-membrane interface. Conventional liposomes used in drug delivery are usually stabilized by the addition of cholesterol and have their bloodstream lifetime extended through the inclusion of PEGylated lipids in the formulation to create a protective polymer corona. For this reason, we tested the effect of these two modifications on the behavior of piroxicam in the membrane. When the bilayer was PEGylated, piroxicam localize to the PEG layer and within the lipid headgroup region. This suggests that PEGylated liposomes are capable of carrying a larger quantity of piroxicam than the conventional ones. [ABSTRACT FROM AUTHOR]