Nanoarchitectonics of Layer-by-Layer (LbL) coated nanostructured lipid carriers (NLCs) for Enzyme-Triggered charge reversal.

HYPOTHESIS: Combined usage of Layer-by-Layer (LbL) coating and alkaline phosphatase (ALP) - responsive charge reversal strategies can improve the cellular internalisation of the colloidal drug delivery systems by also decreasing their cytotoxic effects. EXPERIMENTS: Anionic core NLCs were formed by combining the melt emulsification method and ultrasonication. The resulting core NLCs were coated sequentially first with protamine (Prot NLCs) and then with sodium tripolyphosphate (TPP) or sodium polyphosphate (Graham's salt, PP) generating TPP or PP NLCs, respectively. The developed NLCs were characterised regarding their size and zeta potential. Enzyme-induced charge reversal of the TPP and PP NLCs was evaluated by zeta potential measurements upon their incubation with alkaline phosphatase (ALP). In parallel, time-dependent phosphate release was monitored in the presence of isolated as well as cell-associated ALP. Morphological evaluations were performed by scanning electron microscopy (SEM) studies. Moreover, cell viability and cellular uptake studies were carried out in vitro on Caco-2 cells. FINDINGS: The core NLCs were obtained with a mean size of 272.27 ± 5.23 nm and a zeta potential of -25.70 ± 0.26 mV. Upon coating with protamine, the zeta potential raised to positive values with a total change up to Δ29.3 mV also displaying an increase in particle size. The second layer coating with TPP and PP provided a negative surface charge. Subsequent to ALP treatment, the zeta potential of the TPP and PP NLCs reversed from negative to positive values with total changes of Δ8.56 and Δ7.47 mV, respectively. Conformably, significant amounts of phosphate were released from both formulations. Compared with core NLCs, improved cellular viability as well as increased cellular uptake were observed in case of Prot, TPP and PP NLCs.

Solidification of self-emulsifying drug delivery systems (SEDDS): Impact on storage stability of a therapeutic protein.

Four solidification methods for self-emulsifying drug delivery systems (SEDDS) were compared to evaluate the impact of solidification on storage stability of an incorporated protein. Papain was loaded in SEDDS via hydrophobic ion pairing (HIP). Liquid SEDDS (l-SEDDS) were either solidified by adsorption to solid excipients such as magnesium-aluminometasilicate via wet granulation (ssilica-SEDDS) and carbohydrates via lyophilisation (scarbo-SEDDS) or by incorporation of high-melting PEG-surfactants (sPEG-SEDDS) and triglycerides (soil-SEDDS) in SEDDS preconcentrates. L- and s-SEDDS were compared regarding intrinsic emulsion properties, solid-state form of papain, enzyme stability and activity during storage. HIP with deoxycholate showed a precipitation efficiency of 82% and papain maintained 90% of its initial activity. Incorporated papain was present in an amorphous state, confirming a molecular dispersion in all preconcentrates. In comparison to l-SEDDS each solidification method investigated improved the storage stability of incorporated papain. Neither precipitation nor phase separation was observed for s-SEDDS. sPEG-SEDDS demonstrated with 87.8% the highest enzymatic activity and displayed according to the following rank order: sPEG-SEDDS > soil-SEDDS > ssilica-SEDDS > scarbo-SEDDS > l-SEDDS the highest remaining papain activity after 30 days of storage. This work clearly demonstrates that solidified SEDDS can provide a significantly improved storage stability for therapeutic proteins compared to corresponding liquid formulations.

Grafting of wool fibers through disulfide bonds: An advanced application of S-protected thiolated starch.

The purpose of this study is to develop a potential pathway for grafting polymers onto wool fibers based on thiol-disulfide exchange reactions. S-protected thiolated starch (PTS) was synthesized by coupling 3-(2-pyridyldithio) propanoic acid to starch through esterification, resulting in 417.3 ± 15.1 µmol ligand binding to 1 g of starch. PTS was labelled with fluorescein isothiocyanate (FITC) prior to grafting. Wool fibers were preactivated by raising the amount of thiol groups utilizing mild reducing agents. The highest degree of preactivation on the surface of wool fibers was achieved by a 0.2% (w/v) sodium borohydride and 1.5% (w/v) sodium bisulfite mixture pH 5.0 resulting in 182.6 ± 8.7 µmol thiol groups per gram of fibers. Different incubation times and ratios between FITC-labelled PTS and wool fibers were investigated. A graft yield of 58.5% was achieved at a ratio of 1:1.5 (w/w) between wool fibers and FITC-labelled PTS within 18 h of incubation. Successful coating of PTS on wool fibers was confirmed by confocal imaging, scanning electron microscopy and FT-IR. Mechanical properties of grafted wool fibers were tested regarding elongation and tensile strength. These results provide evidence for the potential of S-protected thiolated starch as a superior coating material for wool fibers.

Zeta Potential Changing Polyphosphate Nanoparticles: A Promising Approach To Overcome the Mucus and Epithelial Barrier.

The aim of the present study was to develop zeta potential-changing polyphosphate nanoparticles (pp-NPs) in order to overcome the diffusion barrier of the mucus gel layer and to provide an enhanced cellular uptake. pp-NPs were obtained by in situ gelation between cationic polyethylene imine and anionic polyphosphate. The resulting pp-NPs were characterized with regard to size and zeta potential. Phosphate release studies were carried out by incubation of pp-NPs with isolated as well as cell-associated intestinal alkaline phosphatase (IAP) and quantified by malachite green assay. Correspondingly, change in the zeta potential was measured, and pp-NPs were analyzed by scanning electron microscopy studies. Mucus permeation studies were performed with porcine intestinal mucus via the transwell insert method and rotating tube method. Furthermore, cell viability and cellular uptake were investigated on Caco-2 cells. The resulting pp-NPs displayed a mean size of 269.16 ± 1.12 nm and a zeta potential between -9 and -10 mV in the characterization studies. Within 4 h, a remarkable amount of phosphate was released from pp-NPs incubated with isolated IAP as well as cell-associated IAP and zeta potential raised up from -9.14 ± 0.45 to -1.75 ± 0.46 mV. Compared with dephosphorylated polyphosphate nanoparticles (de-pp-NPs), a significantly enhanced mucus permeation of pp-NPs was observed. Moreover, pp-NPs did not exhibit cytotoxicity. Cellular uptake increased 2.6-fold by conversion of pp-NPs to de-pp-NPs following enzymatic cleavage. Taking the comparatively simple preparation method and the high mucus-permeating properties of pp-NPs and high cellular uptake properties of de-pp-NPs into account, these nanocarriers might be promising novel tools for mucosal drug delivery.

S-protected gellan gum: Decisive approach towards mucoadhesive antimicrobial vaginal films.

The aim of this study was to synthesize novel polymeric excipients forming mucoadhesive films for treatment of vaginal microbial infections. 2-(2-Amino ethyldisulfanyl) nicotinic acid was conjugated with gellan gum via amide bond formation. The structure of the resulting S-protected gellan gum was confirmed by 1H NMR. S-protected gellan gum variants were characterized for thiol content, cytotoxicity, rheological behaviour and film forming capability. Depending on the added amount of AMENA degree of thiolation was 81 ±â€¯13 (S-GG 81) and 174 ±â€¯16 (S-GG 174) µmol/g, respectively. Vaginal films were casted from S-protected gellan gum variants and studied for adherence to vaginal mucosa, drug release and antimicrobial activity. S-protected gellan gum remained biocompatible showing >87% cell viability. S-GG 81 and S-GG 174 exhibited 1.84- and 4.3-fold increased dynamic viscosity in porcine mucus in comparison to unmodified gellan gum, respectively. Compared to gellan gum films, thiol functionalized gellan gum films showed 3-fold improved adhesion on mucosal surface over a period of 3 h along with significant antimicrobial activity. Moreover, S-protected gellan gum provided a sustained release of metronidazole. According to these results, S-protected gellan gum proved to be a promising novel excipient for casting vaginal films, exhibiting strongly improved mucoadhesive and antimicrobial properties.

Synthesis, Crystal Structure, and Compressibilities of Mn3-x Ir5 B2+x (0≤x≤0.5) and Mn2 IrB2.

The new ternary transition metal borides Mn3-x Ir5 B2+x (0≤x≤0.5) and Mn2 IrB2 were synthesized from the elements under high temperature and high-pressure/high-temperature conditions. Both phases can be synthesized as powder samples in a radio-frequency furnace in argon atmosphere. High-pressure/high-temperature conditions were used to grow single-crystals. The phases represent the first ternary compounds within the system Mn-Ir-B. Mn3-x Ir5 B2+x (0≤x≤0.5) crystallizes in the Ti3 Co5 B2 structure type (P4/mbm; no. 127) with parameters a=9.332(1), c=2.896(2) Å, and Z=2. Mn2 IrB2 crystallizes in the ß-Cr2 IrB2 crystal structure type (Cmcm; no. 63) with parameters a=3.135(3), b=9.859(5), c=13.220(3) Å, and Z=8. The compositions of both compounds were confirmed by EDX measurements and the compressibility was determined experimentally for Mn3-x Ir5 B2+x and by DFT calculations for Mn2 IrB2 .

Li3Co1.06(1)TeO6: synthesis, single-crystal structure and physical properties of a new tellurate compound with CoII/CoIII mixed valence and orthogonally oriented Li-ion channels.

A tellurate compound with CoII/CoIII mixed valence states and lithium ions within orthogonally oriented channels was realized in Li3Co1.06(1)TeO6. The single-crystal structure determination revealed two independent and interpenetrating Li/O and (Co,Te)/O substructures with octahedral oxygen coordination of the metal atoms. In contrast to other mixed oxides, a honeycomb-like ordering of CoO6 and TeO6 octahedra was not observed. Li3Co1.06(1)TeO6 crystallizes orthorhombically with the following unit cell parameters and refinement results: Fddd, a = 588.6(2), b = 856.7(2), c = 1781.5(4) pm, R1 = 0.0174, wR2 = 0.0462, 608 F2 values, and 33 variables. Additional electron density in tetrahedral voids in combination with neighboring face-linked and under-occupied octahedral lithium sites offers an excellent possible diffusion pathway for lithium ions. According to the symmetry of the crystal structure the diffusion pathways in Li3Co1.06(1)TeO6 were found in two orthogonal orientations. The CoII/CoIII mixed valence was investigated via X-ray photoelectron spectroscopy (XPS), revealing a composition comparable to that derived from single-crystal X-ray diffractometry. Magnetic susceptibility measurements underlined the coexistence of CoII and CoIII, the title compound, however, showed no magnetic ordering down to low temperatures. The ionic conductivity of Li3Co1.06(1)TeO6 was determined via alternating current (AC) electrochemical impedance spectroscopy and was found to be in the range of 1.6 × 10-6 S cm-1 at 573 K.

Verbeekite, the Long-Unknown Crystal Structure of Monoclinic PdSe2.

Verbeekite, a monoclinic polymorph of PdSe2, was reported for the first time in 2002 by Roberts et al. The mineral has been discovered in the Musonoi Cu-Co-Mn-U mine, Democratic Republic of Congo, and was named after Dr. Théodore Verbeek, the first geoscientist who studied the palladium mineralization there (1955-1967). Until today, the crystal structure of this very rare mineral has been unknown. By syntheses via multianvil high-pressure/high-temperature methods at 11.5 GPa and 1300 °C, synthetic verbeekite could be obtained in a high degree of purity and comparatively good crystal quality, which made it possible to determine the full crystal structure for PdSe2 verbeekite from single-crystal X-ray diffractometer data: I2/a, a = 671.0(2) pm, b = 415.42(8) pm, c = 891.4(2) pm, ß = 92.42(3)°, V = 248.24(4) Å3, R1 = 0.0368, wR2 = 0.0907 (all data). In contrast to layered PdS2-type PdSe2, verbeekite exhibits a novel crystal structure type of dichalcogenides of the platinum-group metals with (Se2)2- dimer anions connecting the layers. The possibility of different arrangements of the characteristic (Se2)2- dumbbells is the reason for the various polymorphs of the dichalcogenides, with now five known PdSe2 representatives.

Mechanical Properties, Quantum Mechanical Calculations, and Crystallographic/Spectroscopic Characterization of GaNbO4, Ga(Ta,Nb)O4, and GaTaO4.

Single crystals as well as polycrystalline samples of GaNbO4, Ga(Ta,Nb)O4, and GaTaO4 were grown from the melt and by solid-state reactions, respectively, at various temperatures between 1698 and 1983 K. The chemical composition of the crystals was confirmed by wavelength-dispersive electron microprobe analysis, and the crystal structures were determined by single-crystal X-ray diffraction. In addition, a high-P-T synthesis of GaNbO4 was performed at a pressure of 2 GPa and a temperature of 1273 K. Raman spectroscopy of all compounds as well as Rietveld refinement analysis of the powder X-ray diffraction pattern of GaNbO4 were carried out to complement the structural investigations. Density functional theory (DFT) calculations enabled the assignment of the Raman bands to specific vibrational modes within the structure of GaNbO4. To determine the hardness (H) and elastic moduli (E) of the compounds, nanoindentation experiments have been performed with a Berkovich diamond indenter tip. Analyses of the load-displacement curves resulted in a high hardness of H = 11.9 ± 0.6 GPa and a reduced elastic modulus of Er = 202 ± 9 GPa for GaTaO4. GaNbO4 showed a lower hardness of H = 9.6 ± 0.5 GPa and a reduced elastic modulus of Er = 168 ± 5 GPa. Spectroscopic ellipsometry of the polished GaTa0.5Nb0.5O4 ceramic sample was employed for the determination of the optical constants n and k. GaTa0.5Nb0.5O4 exhibits a high average refractive index of nD = 2.20, at λ = 589 nm. Furthermore, in situ high-temperature powder X-ray diffraction experiments enabled the study of the thermal expansion tensors of GaTaO4 and GaNbO4, as well as the ability to relate them with structural features.

Nanoindentation, High-Temperature Behavior, and Crystallographic/Spectroscopic Characterization of the High-Refractive-Index Materials TiTa2O7 and TiNb2O7.

Colorless single crystals, as well as polycrystalline samples of TiTa2O7 and TiNb2O7, were grown directly from the melt and prepared by solid-state reactions, respectively, at various temperatures between 1598 K and 1983 K. The chemical composition of the crystals was confirmed by wavelength-dispersive X-ray spectroscopy, and the crystal structures were determined using single-crystal X-ray diffraction. Structural investigations of the isostructural compounds resulted in the following basic crystallographic data: monoclinic symmetry, space group I2/m (No. 12), a = 17.6624(12) Å, b = 3.8012(3) Å, c = 11.8290(9) Å, ß = 95.135(7)°, V = 790.99(10) Å(3) for TiTa2O7 and a = 17.6719(13) Å, b = 3.8006(2) Å, c = 11.8924(9) Å, ß = 95.295(7)°, V = 795.33(10) Å(3), respectively, for TiNb2O7, Z = 6. Rietveld refinement analyses of the powder X-ray diffraction patterns and Raman spectroscopy were carried out to complement the structural investigations. In addition, in situ high-temperature powder X-ray diffraction experiments over the temperature range of 323-1323 K enabled the study of the thermal expansion tensors of TiTa2O7 and TiNb2O7. To determine the hardness (H), and elastic moduli (E) of the chemical compounds, nanoindentation experiments have been performed with a Berkovich diamond indenter tip. Analyses of the load-displacement curves resulted in a hardness of H = 9.0 ± 0.5 GPa and a reduced elastic modulus of Er = 170 ± 7 GPa for TiTa2O7. TiNb2O7 showed a slightly lower hardness of H = 8.7 ± 0.3 GPa and a reduced elastic modulus of Er = 159 ± 4 GPa. Spectroscopic ellipsometry of the polished specimens was employed for the determination of the optical constants n and k. TiNb2O7 as well as TiTa2O7 exhibit a very high average refractive index of nD = 2.37 and nD = 2.29, respectively, at λ = 589 nm, similar to that of diamond (nD = 2.42).

A synthesis and crystal chemical study of the fast ion conductor Li(7-3x)Ga(x)La3 Zr2O12 with x = 0.08 to 0.84.

Fast-conducting phase-pure cubic Ga-bearing Li7La3Zr2O12 was obtained using solid-state synthesis methods with 0.08 to 0.52 Ga(3+) pfu in the garnet. An upper limit of 0.72 Ga(3+) pfu in garnet was obtained, but the synthesis was accompanied by small amounts of La2Zr2O12 and LiGaO3. The synthetic products were characterized by X-ray powder diffraction, electron microprobe and SEM analyses, ICP-OES measurements, and (71)Ga MAS NMR spectroscopy. The unit-cell parameter, a0, of the various garnets does not vary significantly as a function of Ga(3+) content, with a value of about 12.984(4) Å. Full chemical analyses for the solid solutions were obtained giving: Li7.08Ga0.06La2.93Zr2.02O12, Li6.50Ga0.15La2.96Zr2.05O12, Li6.48Ga0.23La2.93Zr2.04O12, Li5.93Ga0.36La2.94Zr2.01O12, Li5.38Ga0.53La2.96Zr1.99O12, Li4.82Ga0.60La2.96Zr2.00O12, and Li4.53Ga0.72La2.94Zr1.98O12. The NMR spectra are interpreted as indicating that Ga(3+) mainly occurs in a distorted 4-fold coordinated environment that probably corresponds to the general 96h crystallographic site of garnet.

High-pressure synthesis and characterization of the first cerium fluoride borate CeB2O4F.

CeB2O4F is the first cerium fluoride borate, which is exclusively built up of one-dimensional, infinite chains of condensed trigonal-planar [BO3]3- groups. This new cerium fluoride borate was synthesized under high-pressure/high-temperature conditions of 0.9 GPa and 1450 °C in a Walker-type multianvil apparatus. The compound crystallizes in the orthorhombic space group Pbca (No. 61) with eight formula units and the lattice parameters a=821.63(5), b=1257.50(9), c=726.71(6) pm, V=750.84(9) Å3, R1=0.0698, and wR2=0.0682 (all data). The structure exhibits a 9+1 coordinated cerium ion, one three-fold coordinated fluoride ion and a one-dimensional chain of [BO3]3- groups. Furthermore, IR spectroscopy, Electron Micro Probe Analysis and temperature-dependent X-ray powder diffraction measurements were performed.

Monoclinic structure and nonstoichiometry of 'KAlSiO4-O1'.

Crystals of KAlSiO4-O1 (potassium aluminium silicate) were synthesized using a flux method and analysed utilizing single-crystal X-ray diffraction and electron microprobe analysis. Both methods confirm that the crystals are nonstoichiometric according to K(1-x)Al(1-x)Si(1+x)O4 with x = 0.04 (1). KAlSiO4-O1 is closely related to the stuffed derivatives of tridymite, although the topology of the Si/Al-ordered framework is different. Six-membered rings of UUDDUD and UUUDDD (U = up and D = down; ratio 2:1) configurations are present in layers parallel to the ab plane. In contrast, the framework of tridymite exhibits UDUDUD rings. The crystals are affected by inversion, pseudo-orthorhombic and pseudo-hexagonal twinning.