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Poly(ester amide)s (PEAs) are lacking in structural and spectroscopic information. This paper reports a structural and spectroscopic characterization of Nα-benzoyl-L-argininate ethyl ester chloride (BAEEH+·Cl-), an important amino acid derivative and an adequate PEAs' model compound. Crystals of BAEEH+·Cl- obtained by slow evaporation in an ethanol/water mixture were studied by different complementary techniques. X-ray analysis shows that BAEEH+·Cl- crystallizes in the chiral space group P21. There are two symmetry independent cations (and anions) in the unit cell. The two cations have different conformations: in one of them, the angle between the least-squares planes of the phenyl ring and the guanidyl group is 5.1(2)º, and in the other the corresponding angle is 13.3(2)º. There is an extensive network of H-bonds that assembles the ions in layers parallel to the ab plane. Experimental FT-IR and Raman spectra of BAEEH+·Cl- were recorded at room temperature in the 3750-600 cm-1 and 3380-100 cm-1 regions, respectively, and fully assigned. Both structural and spectroscopic analysis were supported by quantum chemistry calculations based on different models (in vacuo and solid-state DFT simulations). [ABSTRACT FROM AUTHOR]

Abstract: This work reports and discusses the influence of four phosphonium-based ionic liquids (PhILs), namely trihexyl(tetradecyl) phosphonium dicyanamide, [P6,6,6,14][dca]; trihexyl(tetradecyl) phosphonium bis(trifluoromethylsulfonyl)imide, [P6,6,6,14][Tf2N]; tetrabutyl phosphonium bromide, [P4,4,4,4][Br]; and tetrabutyl phosphonium chloride, [P4,4,4,4][Cl], on some of the chemical, physical and biological properties of a biomedical-grade suspension of poly(vinyl chloride) (PVC). The main goal of this work was to evaluate the capacity of these PhILs to modify some of the properties of neat PVC, in particular those that may allow their use as potential alternatives to traditional phthalate-based plasticizers in PVC biomedical applications. PVC films having different PhIL compositions (0, 5, 10 and 20wt.%) were prepared (by solvent film casting) and characterised by Fourier transform infrared, thermogravimetric analysis, differential scanning calorimetry, dynamical mechanical thermal analysis, scanning electron microscopy/energy-dispersive X-ray/electron probe microanalysis, X-ray diffraction, transmittance, permeability towards oxygen and carbon dioxide, thermal degradation, contact angle measurement, water and vapour uptake, leachability and biocompatibility (haemolytic potential, thrombogenicity and cytotoxicity). A conventional organic plasticizer (di-isononyl phthalate) was used for comparison purposes. The results obtained showed that it was possible to change the neat PVC hydrophobicity, and consequently its water uptake capacity and plasticizer leachability, just by changing the PhIL employed and its composition. It was also possible to significantly change the thermal and mechanical properties of PVC films by choosing appropriate PhIL cation/anion combinations. However, a specific PhIL may not always be capable of simultaneously keeping and/or improving both physical properties. In addition, ionic halide salts were found to promote PVC dehydrochlorination. Finally, none of the prepared materials presented toxicity against Caco-2 cells, though pure [P6,6,6,14][dca] decreased HepG2 cells viability. Moreover, PVC films with [P6,6,6,14][dca] and [P4,4,4,4][Cl] were found to be haemolytic and thus these PhILs must be avoided as PVC modifiers if biomedical applications are envisaged. In conclusion, from all the PhILs tested, [P6,6,6,14][Tf2N] showed the most promising results regarding blood compatibility, leaching and permeability to gases of PVC films. The results presented are a strong indicator that adequate PhILs may be successfully employed as PVC multi-functional plasticizers for a wide range of potential applications, including those in the biomedical field. [Copyright &y& Elsevier]

Iron deficiency is the most common nutritional deficit worldwide. The goal of this work was to obtain iron-pectin beads by ionic gelation and evaluate their physiological behavior to support their potential application in the food industry. The beads were firstly analyzed by scanning electronic microscopy, and then physical-chemically characterized by performing swelling, thermogravimetric, porosimetry, Mössbauer spectroscopy and X-ray fluorescence analyses, as well as by determining the particle size. Then, physiological assays were carried out by exposing the beads to simulated gastric and intestinal environments, and determining the iron absorption and transepithelial transport into Caco-2/TC7 cells. Iron-pectin beads were spherical (diameter 1-2 mm), with high density (1.29 g/mL) and porosity (93.28%) at low pressure, indicating their high permeability even when exposed to low pressure. Swelling in simulated intestinal medium (pH 8) was higher than in simulated gastric medium. The source of iron [FeSO 4 (control) or iron-pectin beads] did not have any significant effect on the mineral absorption. Regarding transport, the iron added to the apical pole of Caco-2/TC7 monolayers was recovered in the basal compartment, and this was proportional with the exposure time. After 4 h of incubation, the transport of iron arising from the beads was significantly higher than that of the iron from the control (FeSO 4 ). For this reason, iron-pectin beads appear as an interesting system to overcome the low efficiency of iron transport, being a potential strategy to enrich food products with iron, without altering the sensory properties., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Liposomes are exceptional carriers for therapeutic drug delivery. However, they generally suffer from poor cell penetration, low half-life in bloodstream and loss of functionality during storage. To overcome these problems some strategies can be applied, such as functionalization with polymers and the use of protective molecules during dehydration processes. This work reports a complete study about the stability, including freeze-drying in the presence of trehalose, storage and internalization into HEp-2 cells, of stable formulations of pH sensitive polymer-liposome complexes (PLC) composed of soybean lecithin and crosslinked/non-crosslinked poly(acrylic acid) with a cholesterol end-group (CHO-PAA). The results showed that the average hydrodynamic particle size of the complexes persisted unaffected for approximately 75 days after freeze-drying in the presence of 10% w/v trehalose. The efficiency of calcein encapsulation and release profiles in physiologic conditions exhibited no significant alterations when stored for 0 and 1 month, and for 2 and 3 months of storage the calcein release increased with time. The stored complexes were efficiently uptaken into HEp-2-cells, as determined by confocal microscopy. In all cases, the percentage of viable cells was above 90%, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, indicating no potential toxicity. Finally, transepithelial transport assays demonstrated that both fresh and 2 months-stored complexes could transport their calcein content through HEp-2 monolayers over time., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Liposomes are generally used as delivery systems, as they are capable of encapsulating a wide variety of molecules (i.e. plasmids, recombinant proteins, therapeutic drugs). However, liposomal drug delivery have to fulfill different requirements, such as the effective internalization by the target cells and avoidance of the degradative activity of the intracellular compartments. The use of polymer lipid complexes (PLCs), by including different polymers in the liposome formulation, could improve internalization and intracellular release of drugs. The aim of the present work is to study the mechanisms of cellular uptaking and the intracellular trafficking of PLCs formed with cholesterol-poly(2-(dimethylamino)ethyl methacrylate) CHO-PDMAEMA and lecithin (LC CHO-PD). Calcein-loaded liposomes were used to determine cellular uptake and intracellular localization by flow cytometry and confocal microscopy. Incorporation of CHO-PDMAEMA to lecithin liposomes enhanced the internalization capacity of PLCs. Internalization of PLCs by human epithelial-like cells (HEK-293) diminished at 4°C, suggesting uptake by endocytosis. PLCs showed no co-localization with acidic compartments after internalization. Experiments with endocytosis inhibitors and co-localization of liposomes and albumin, suggested the caveolae endocytic pathway as the most probable route for intracellular trafficking of PLCs. In this work, we demonstrated an efficient uptake of LC CHO-PDs by human epithelial-like cells (HEK-293) through the non-degradative caveolae endocytic pathway. The mode of internalization and the intracellular fate of liposomes under study, suggest a promising use of LC CHO-PDs as drug delivery systems., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The development of polymer-liposome complexes (PLCs), in particular for biomedical applications, has grown significantly in the last decades. The importance of these studies comes from the emerging need in finding intelligent controlled release systems, more predictable, effective and selective, for applications in several areas, such as treatment and/or diagnosis of cancer, neurological, dermatological, ophthalmic and orthopedic diseases, gene therapy, cosmetic treatments, and food engineering. This work reports the development and characterization of a pH sensitive system for controlled release based on PLCs. The selected hydrophilic polymer was poly(acrylic acid) (PAA) synthesized by atom transfer radical polymerization (ATRP) with a cholesterol (CHO) end-group to improve the anchoring of the polymer into the lipid bilayer. The polymer was incorporated into liposomes formulated from soybean lecithin and stearylamine, with different stearylamine/phospholipid and polymer/phospholipid ratios (5, 10 and 20%). The developed PLCs were characterized in terms of particle size, polydispersity, zeta potential, release profiles, and encapsulation efficiency. Cell viability studies were performed to assess the cytotoxic potential of PLCs. The results showed that the liposomal formulation with 5% of stearylamine and 10% of polymer positively contribute to the stabilization of the complexes. Afterwards, the carboxylic acid groups of the polymer present at the surface of the liposomes were crosslinked and the same parameters analyzed. The crosslinked complexes showed to be more stable at physiologic conditions. In addition, the release profiles at different pHs (2-12) revealed that the obtained complexes released all their content at acidic conditions. In summary, the main accomplishments of this work are: (i) innovative synthesis of cholesterol-poly(acrylic acid) (CHO-PAA) by ATRP; (ii) stabilization of the liposomal formulation by incorporation of stearylamine and CHO-PAA; (iii) new approach for CHO-PAA crosslinking, resulting in more stable PLCs at physiological conditions; (iv) destabilization of PLCs upon slight changes of pH, showing their pH sensitivity; and (v) the PLCs do not exhibit cellular toxicity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The physicochemical characterization of polymer liposome complexes (PLCs) prepared with lipids of lactic acid bacteria and poly(N,N-dimethylaminoethyl methacrylate) covalently bound to cholesterol (CHO-PDMAEMA) was carried out in an integrated approach, including their stability upon preservation and incorporation into eukaryotic cells. PLCs were prepared with different polymer:lipid molar ratios (0, 0.05 and 0.10). Zeta potential, particle size distribution and polydispersity index were determined. The optimal polymer:lipid ratio and the stability of both bare liposomes and PLCs were evaluated at 37 °C and at different pHs, as well as after storage at 4 °C, -80 °C and freeze-drying in the presence or absence of trehalose 250 mM. Internalization of PLCs by eukaryotic cells was assessed to give a complete picture of the system. Incorporation of CHO-PDMAEMA onto bacterial lipids (ratio 0.05 and 0.10) led to stabilization at 37 °C and pH 7. A slight decrease of pH led to their strong destabilization. Bacteria PLCs showed to be more stable than lecithin (LEC) PLCs (used for comparison) upon preservation at 4 and -80 °C. The harmful nature of the preservation processes led to a strong decrease in the stability of PLCs, bacterial formulations being more stable than LEC PLCs. The addition of trehalose to the suspension of liposomes stabilized LEC PLC and did not have effect on bacterial PLCs. In vitro studies on Raw 264.7 and Caco-2/TC7 cells demonstrated an efficient incorporation of PLCs into the cells. Preparations with higher stability were the ones that showed a better cell-uptake. The nature of the lipid composition is determinant for the stability of PLCs. Lipids from lactic acid bacteria are composed of glycolipids and phospholipids like cardiolipin and phosphatidylglycerol. The presence of negatively charged lipids strongly improves the interaction with the positively charged CHO-PDMAEMA, thus stabilizing liposomes. In addition, glycolipids and phosphatidylglycerol act as intrinsic protectants of PLCs upon preservation. This particular lipid composition of lactic acid bacteria makes them natural formulations potentially useful as drug delivery systems., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The development of new polymer-liposome complexes (PLCs) as delivery systems is the key issue of this work. Three main areas are dealt with: polymer synthesis/characterization, liposome formulation/characterization and evaluation of the PLCs uptake by eukaryotic cells. Poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) with low molecular weight and narrow polydispersity was synthesized by Atom Transfer Radical Polymerization (ATRP). The polymers were synthesized using two different bromide initiators (cholesteryl-2-bromoisobutyrate and ethyl 2-bromoisobutyrate) as a route to afford PDMAEMA and CHO-PDMAEMA. Both synthesized polymers (PDMAEMA and CHO-PDMAEMA) were incorporated in the preparation of lecithin liposomes (LEC) to obtain PLCs. Three polymer/lipid ratios were investigated: 5, 10 and 20%. Physicochemical characterization of PLCs was carried out by determining the zeta potential, particle size distribution, and the release of fluorescent dyes (carboxyfluorescein CF and calcein) at different temperatures and pHs. The leakage experiments showed that CHO covalently bound to PDMAEMA strongly stabilizes PLCs. The incorporation of 5% CHO-PDMAEMA to LEC (LEC_CHO-PD5) appeared to be the stablest preparation at pH 7.0 and at 37°C. LEC_CHO-PD5 destabilized upon slight changes in pH and temperature, supporting the potential use of CHO-PDMAEMA incorporated to lecithin liposomes (LEC_CHO-PDs) as stimuli-responsive systems. In vitro studies on Raw 264.7 and Caco-2/TC7 cells demonstrated an efficient incorporation of PLCs into the cells. No toxicity of the prepared PLCs was observed according to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. These results substantiate the efficiency of CHO-PDMAEMA incorporated onto LEC to assist for the release of the liposome content in mildly acidic environments, like those found in early endosomes where pH is slightly lower than the physiologic. In summary, the main achievements of this work are: (a) novel synthesis of CHO-PDMAEMA by ATRP, (b) stabilization of LEC by incorporation of CHO-PDMAEMA at neutral pH and destabilization upon slight changes of pH, (c) efficient uptake of LEC_CHO-PDs by phagocytic and non-phagocytic eukaryotic cells., (Copyright © 2012 Elsevier B.V. All rights reserved.)

L-Lactic acid (L-LA) oligomers (up to the pentamer) were studied by three complementary approaches: vibrational (IR and Raman) and NMR ((1)H and (13)C) spectroscopies and DFT calculations. Vibrational and NMR spectra of L-LA oligomers and poly(L-lactic acid) (PLLA) homopolymer were recorded at room temperature and interpreted. Further insight into the structures (conformations) of the title systems was provided by theoretical B3LYP/6-311++G(d,p) studies. Calculated energies and computed vibrational and NMR spectra of the most stable conformers of L-LA oligomers, together with the experimental vibrational and NMR spectra, enabled the characterization of the preferred conformations adopted by PLLA chains.

This paper provides an overview of recent progress on structural data on the title compound. Theoretical work based on quantum mechanical calculations was performed to gain some understanding on the heterocyclic tautomerism potentially exhibited by the compound. The computational studies encompassed a wide range of tautomers/conformers, allowing the determination of the most probable molecular structure. In the gas phase, the nitroimine tautomers are computed to be substantially more stable than the nitramine tautomers. Among three plausible nitroimine forms, special attention was given to 4,6-bis(nitroimino)-1,3,5-triazinan-2-one, whose crystal structure was unequivocally solved by X-ray diffraction. The crystals are orthorhombic, space group Pnma with a = 6.187(2)A, b = 13.252(5)A, c = 8.802(4)A, and Z = 4. The structure was solved by direct methods and refined to a final R = 0.0326. The molecule has an approximate mirror plane relating the two symmetry related halves. The nitroimine groups are positioned in a syn-syn conformation. The least-squares (LS) plane of the heterocyclic ring and the nitroimine ([double bond]N-NO2) substituent LS plane make an angle of 10.05(11) degrees. The crystal structure is held together via hydrogen bonds that assemble the molecules in chains running along the b-axis. Every H-atom is involved in bifurcated hydrogen bonds.