Dynamic Behavior of the Structural Phase Transition of Hydrogel Formation Induced by Temperature Ramp and Addition of Ibuprofen.

Understanding the dynamic behavior of hydrogel formation induced by a temperature ramp is essential for the design of gel-based injectable formulation as drug-delivery vehicles. In this study, the dynamic behavior of the hydrogel formation of Pluronic F108 aqueous solutions within different heating rates was explored in both macroscopic and microscopic views. It was discovered that when the heating rate is increased, the gelation temperature window (hard gel region) shrinks and the mechanical strength of the hydrogel decreases. A given system at different heating rates would lead to different crystalline structural evolutions. The time-resolved small-angle X-ray scattering (SAXS) experiments at a heating rate of 10 °C/min disclose that the crystalline structure of micelle packing in the hydrogel exhibits a series of transitions: hexagonal close-packed (HCP) to face-centered cubic (FCC) and body-centered cubic (BCC) structures coexisting and then to the BCC structure along with the increasing temperature. For the system at equilibrium, the BCC structure exclusively dominates the system. Furthermore, the addition of a hydrophobic model drug (ibuprofen) to the F108 aqueous solution promotes hard gel formation at even lower temperatures and concentrations of F108. The SAXS results for the system with ibuprofen at a heating rate of 10 °C/min demonstrate a mixture of FCC and BCC structures coexisting over the whole gelation window compared to the BCC structure that exclusively dominates the system at equilibrium. The addition of ibuprofen would alter the structural evolution to change the delivery path of the encapsulated drug, which is significantly related to the performance of drug release.

Role of molecular weight and hydrophobicity of amphiphilic tri-block copolymers in temperature-dependent co-micellization process and drug solubility.

The binary P123 + F108, + F98, + F88, + F68, + F87 and + P84 systems were used to systematically explore the effect of molecular weight and hydrophobicity of Pluronic on the tendency of cooperative binding between parent copolymers and solubility of drug (ibuprofen) in these mixed Pluronic systems. Temperature-dependent co-micellization process in these systems was carefully investigated by using high sensitivity differential scanning calorimeter (HSDSC), dynamic light scattering (DLS) and small angle X-ray scattering (SAXS). All the HSDSC thermograms for these systems consistently exhibit two endothermic (micellization) peaks apart by at least 13.3 °C. It was evidenced that micelles are mainly formed by P123, the copolymer with a lower critical micelle temperature (CMT), at low temperatures. Raising temperature would dehydrate the other Pluronic with a higher CMT to be integrated into the neat P123 micelles developed at low temperatures. When the temperature is further increased beyond the second endothermic peak, the mixed micelles with a two-shell structure and characteristic corona lengths of their parent copolymers are observed to prove the existence of cooperative binding between parent copolymers. All the binary mixed Pluronic systems used in this study exhibit cooperative binding to form unimodal distribution of mixed micelles, except the P123 + F68 system. The SAXS results show that P123 + F68 system at 65 °C exhibits bimodal distribution of aggregates with coexisting of neat F68 micelles (65% in number) and P123 + F68 mixed micelles (35% in number). It is interesting to find out that P123 and F68 with distinct polypropylene oxide (PPO) moieties (i.e., a difference of 37 PO units) would exhibit very weak cooperative binding to partially form mixed micelles. Addition of ibuprofen in the P123 + F68 system would substantially enhance the cooperative binding between P123 and F68 to form bimodal distribution of aggregates with coexisting of neat F68 micelles (drops down to 30% in number) and P123 + F68 mixed micelles (increases up to 70% in number). For the systems with ibuprofen incorporated, SAXS results demonstrate that the drug is mainly encapsulated in the core of neat micelles developed at low temperatures. The solubility of ibuprofen in the 0.5 wt% P123 + 0.368 wt% P84 system is as high as 2.62 mg/ml, which is 114 times more than that in pure water at 37 °C.

Small-Angle X-ray Scattering Studies on the Structure of Disc-Shaped Bicelles Incorporated with Neutral PEGylated Lipids.

In this study, small-angle X-ray scattering (SAXS) is successfully employed to investigate the structure of the DPPC/diC7PC disc-shaped bicelles incorporated with different amounts of C16-PEG2000-Ceramide lipids. The incorporation of the C16-PEG2000-Ceramide lipids could provide an antifouling capability to the bicelle for biomedical applications. However, traditionally it is believed that most of the incorporated PEGlylated lipids should lie in the rim of the disc-shaped bicelle. In this study, high sensitivity SAXS reveals the distribution of the added C16-PEG2000-Ceramide lipids in both the planar region and in the rim of the bicelle. The PEG brushes of C16-PEG2000-Ceramide lipids form a second shell outside the lipid headgroup shell of the bicelle. A double shell disc bicelle model is used in analyzing the SAXS data. The lipid density of C16-PEG2000-Ceramide in the rim is found to be about 1.7 times the C16-PEG2000-Ceramide lipid density in the planar region for all three C16-PEG2000-Ceramide concentrations, 1, 2, and 3 mM. Moreover, the bicelle core radius can be predicted well using the actual molecular ratio of lipids in the planar region to the lipids in the rim of the bicelles in the model calculation.

The adsorption of DNA by cationic core-shell diblock copolymer polystyrene-block-poly(N-methyl 4-vinylpyridine iodide) micelles.

The diblock copolymer polystyrene-block-poly(N-methyl 4-vinylpyridine iodide) (PS-b-P4VPQ) with the molecular weight of PS 3.5 × 103 g/mol and P4VPQ 11.6 × 103 g/mol forms core-shell polymer micelles in aqueous solution. The cationic brush shell of the polymer micelle can be used to accommodate hydrophilic drugs and biomolecules, such as DNA, for biomedical applications. It is essential to understand how biomolecules are adsorbed within the brush layer. Here we investigated the interaction of the cationic brush of the polymer micelle with DNA by small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM). It is found when adding only relatively small amounts of on average 30 base pairs (bp) DNA, at 19.6 and 39.2 µM for 0.1 mM PS-b-P4VPQ, most of the polymer micelle/DNA complexes remain well dispersed. The brush layer of the polymer micelles are slightly swelled due to the adsorption of DNA within the brush layer. When the DNA concentration is increased to 58.8 µM or higher, the polymer micelle/DNA complexes form closely packed agglomerates. At high DNA concentrations, some adsorbed DNA will start to build up at the edge or surface of the brush layer which could induce aggregation of the polymer micelle/DNA complexes. This means that it is possible to prepare mostly dispersed polymer/DNA complexes by keeping the DNA concentration below the aggregation concentration. The well dispersed polymer micelle/DNA complexes are advantageous for many DNA related biomedical applications.

The Penetration Depth for Hanatoxin Partitioning into the Membrane Hydrocarbon Core Measured with Neutron Reflectivity.

Hanatoxin (HaTx) from spider venom works as an inhibitor of Kv2.1 channels, most likely by interacting with the voltage sensor (VS). However, the way in which this water-soluble peptide modifies the gating remains poorly understood as the VS is deeply embedded within the bilayer, although it would change its position depending on the membrane potential. To determine whether HaTx can indeed bind to the VS, the depth at which HaTx penetrates into the POPC membranes was measured with neutron reflectivity. Our results successfully demonstrate that HaTx penetrates into the membrane hydrocarbon core (∼9 Šfrom the membrane surface), not lying on the membrane-water interface as reported for another voltage sensor toxin (VSTx). This difference in penetration depth suggests that the two toxins fix the voltage sensors at different positions with respect to the membrane normal, thereby explaining their different inhibitory effects on the channels. In particular, results from MD simulations constrained by our penetration data clearly demonstrate an appropriate orientation for HaTx to interact with the membranes, which is in line with the biochemical information derived from stopped-flow analysis through delineation of the toxin-VS binding interface.

X-ray Reflectivity Studies on the Mixed Langmuir-Blodgett Monolayers of Thiol-Capped Gold Nanoparticles, Dipalmitoylphosphatidylcholine, and Sodium Dodecyl Sulfate.

Langmuir-Blodgett monolayers of thiolated gold nanoparticles mixed with dipalmitoylphosphatidylcholine/sodium dodecyl sulfate (DPPC/SDS) were investigated by combining the X-ray reflectivity, grazing-incident scattering, and TEM analyses to reveal the in-depth and in-plane organization and the 2D morphology of such mixed monolayers. It was found that the addition of a charged single-tail surfactant to the thiolated Au nanoparticle monolayer helps to stabilize the Au nanoparticle monolayer and to strengthen the mechanical property of the mixed monolayer film. For mixing with lipids, it was found that the thiolated gold nanoparticles could be pushed on top of the lipid monolayer when the mixed monolayer is compressed. At a typical comparable total surface area ratio of gold nanoparticle to lipid, the thiolated gold nanoparticles could form a uniform domain on top of the DPPC monolayer. When there are more thiolated gold nanoparticles than that could be supported by the lipid monolayer, domain overlapping could occur to form bilayer gold nanoparticle domains at some regions. At low total surface area ratio of thiolated gold nanoparticle to lipid, the thiolated gold nanoparticles tend to form a connected threadlike aggregation structure. Evidently, the morphology of the thiolated gold nanoparticle monolayer is highly depending on the total surface area ratio of the thiolated gold nanoparticle to lipid. SDS is found to have a dispersion power capable of dispersing the originally uniform Au-8C nanoparticle domain of the mixed Au-8C/DPPC monolayer into a foamlike structure for the mixed Au-8C/SDS/DPPC monolayer. It is evident that not only the concentration ratio but also the size and shape of the template formed by the amphiphilic molecules and their interaction with the thiolated gold nanoparticles can all have great effects on the organizational structure as well as morphology of the thiolated gold nanoparticle monolayer.

Hanatoxin inserts into phospholipid membranes without pore formation.

Hanatoxin (HaTx), a 35-residue polypeptide from spider venom, functions as an inhibitor of Kv2.1 channels by interacting with phospholipids prior to affecting the voltage-sensor. However, how this water-soluble peptide modifies the gating remains poorly understood, as the voltage-sensor is deeply embedded within the bilayer. To determine how HaTx interacts with phospholipid bilayers, in this study, we examined the toxin-induced partitioning of liposomal membranes. HPLC-results from high-speed spin-down vesicles with HaTx demonstrated direct binding. Dynamic light scattering (DLS) and leakage assay results further indicated that neither membrane pores nor membrane fragmentations were observed in the presence of HaTx. To clarify the binding details, Langmuir trough experiments were performed with phospholipid monolayers by mimicking the external leaflet of membrane bilayers, indicating the involvement of acyl chains in such interactions between HaTx and phospholipids. Our current study thus describes the interaction pattern of HaTx with vesicle membranes, defining a membrane-partitioning mechanism for peptide insertion involving the membrane hydrocarbon core without pore formation.

Small-Angle Neutron Scattering Studies on the Multilamellae Formed by Mixing Lamella-Forming Cationic Diblock Copolymers with Lipids and Their Interaction with DNA.

We demonstrate that the lamella-forming polystyrene-block-poly(N-methyl-4-vinylpyridinium iodine) (PS-b-P4VPQ), with similar sizes of the PS and P4VPQ blocks, can be dispersed in the aqueous solutions by forming lipid/PS-b-P4VPQ multilamellae. Using small-angle neutron scattering (SANS) and 1,2-dipalmitoyl-d62-sn-glycero-3-phosphocholine (d62-DPPC) in D2O, a broad correlation peak is found in the scattering profile that signifies the formation of the loosely ordered d62-DPPC/PS-b-P4VPQ multilamellae. The thicknesses of the hydrophobic and hydrophilic layers of the d62-DPPC/PS-b-P4VPQ multilamellae are close to the PS layer and the condensed brush layer thicknesses as determined from previous neutron reflectometry studies on the PS-b-P4VPQ monolayer at the air-water interface. Such well-dispersed d62-DPPC/PS-b-P4VPQ multilamellae are capable of forming multilamellae with DNA in aqueous solution. It is found that the encapsulation of DNA in the hydrophilic layer of the d62-DPPC/PS-b-P4VPQ multilamellae slightly increases the thickness of the hydrophilic layer. Adding CaCl2 can enhance the DNA adsorption in the hydrophilic brush layer, and it is similar to that observed in the neutron reflectometry study of the DNA adsorption by the PS-b-P4VPQ monolayer.

Gold atomic clusters extracting the valence electrons to shield the carbon monoxide passivation on near-monolayer core-shell nanocatalysts in methanol oxidation reactions.

Atomic-scale gold clusters were intercalated at the inter-facet corner sites of Pt-shell Ru-core nanocatalysts with near-monolayer shell thickness. We demonstrated that these unique clusters could serve as a drain of valence electrons in the kink region of the core-shell heterojunction. As jointly revealed by density functional theory calculations and valence band spectra, these Au clusters extract core-level electrons to the valence band. They prevent corrosion due to protonation and enhance the tolerance of CO by increasing the electronegativity at the outermost surface of the NCs during the methanol oxidation reaction (MOR). In these circumstances, the retained current density of Pt-shell Ru-core NCs is doubled in a long-term (2 hours) MOR at a fixed voltage (0.5 V vs. SCE) by intercalating these sub-nanometer gold clusters. Such novel structural confinement provides a possible strategy for developing direct-methanol fuel cell (DMFC) modules with high power and stability.

A time-resolved study on the interaction of oppositely charged bicelles--implications on the charged lipid exchange kinetics.

Time-resolved small-angle X-ray scattering was applied to study charged lipid exchange between oppositely charged disc-shaped bicelles. The exchange of charged lipids gradually reduces the surface charge density and weakens the electrostatic attraction between the oppositely charged bicelles which form alternately stacked aggregates upon mixing. Initially, at a high surface charge density with almost no free water layer between the stacked bicelles, fast exchange kinetics dominate the exchange process. At a later stage with a lower surface charge density and a larger water gap between the stacked bicelles, slow exchange kinetics take over. The fast exchange kinetics are correlated with the close contact of the bicelles when there is almost no free water layer between the tightly bound bicelles with a charged lipid exchange time constant as short as 20-40 min. When the water gap becomes large enough to have a free water layer between the stacked bicelles, the fast lipid exchange kinetics are taken over by slow lipid exchange kinetics with time constants around 200-300 min, which are comparable to the typical time constant of lipid exchange between vesicles in aqueous solution. These two kinds of exchange mode fit well with the lipid exchange models of transient hemifusion for the fast mode and monomer exchange for the slow mode.

Formation of divalent ion mediated anionic disc bicelle-DNA complexes.

Disc-shaped bicelles are formed by mixing long-chain lipids with short-chain lipids at suitable molar ratios and they have a relatively uniform size, typically around a few tens of nanometers in diameter. Different from the typically formulated cationic or anionic liposome­DNA complexes, which are used as nonviral vectors for improving the transfection efficiency of gene therapy, a novel way of packing the DNA can be developed by using the much smaller disc-like bicelles. We demonstrate that anionic lipid bicelle-ion­DNA (AB­DNA) complexes can be formed with the help of divalent ions. Multi-stacked AB­DNA complexes can be formed with diameters of around 50­100 nm and lengths of around 50­150 nm as revealed by TEM. Using the anionic lipid­DNA complexes has the advantage of lower cytotoxicity than using cationic lipids. The interaction of DNA with anionic bicelles was investigated by SAXS. It was found that the anionic bicelle could not form stable complexes with DNA at low calcium ion concentrations, such as 1 mM. The AB­DNA complexes can be formed in the investigated range of 10 mM to 100 mM calcium ion concentrations. However, for an equal anionic lipid charge and DNA charge system, an ion-membrane phase (multilamellar vesicles) would gradually appear as the calcium ion concentration is increased above a critical concentration. It indicates that DNA could be packed closer at above the critical divalent ion concentration. If more DNA is added to such a two-phase coexistence system (originally with the total anionic lipid charge equal to that of DNA), the ion-membrane phase could be transformed into the AB­DNA complexes. As a result, more DNA can be packed in the form of AB­DNA complexes at above the critical calcium ion concentration.

Capacitive performance enhancements of RuO2 nanocrystals through manipulation of preferential orientation growth originated from the synergy of Pluronic F127 trapping and annealing.

The capacitive performances of RuO2 prepared by oxidation precipitation of Ru precursors (RuCl3·xH2O) surrounded with tri-block co-polymer, Pluronic F127, in aqueous media can be enhanced through manipulating its preferential orientation growth of nanocrystals. From the heterogeneous surface chemistry viewpoints with the support of structure characterizations, such enhancement originates from the preferential orientation growth of the {101} facet due to the adsorption of the highly polarisable, non-ionic ligands of Pluronic F127 on the high surface energy facets on RuO2 nanocrystallites. In this case, the F127-trapped sample with annealing at 300 °C enhances the specific capacitance 1.6-fold in comparison to its counterpart without F127. With the mechanistic insight into the heterogeneous surface crystal growth pathways, our results materialize the development of RuO2 with tuneable capacitive performances. Furthermore, due to the different propagation models of RuO2 with and without F127 trapping, a schematic diagram is proposed to interpret such a unique crystal growth evolution phenomenon.

Atomic distribution and structural evolution of mesostructured PtRu nanoparticles electrodeposited on a microemulsion lyotropic liquid-crystalline template probed using EXAFS and XANES.

Mesostructured PtRu nanoparticles were electrochemically reduced from their metallic salts directed by a hexagonally packed microemulsion lyotropic liquid-crystalline (MLLC) template. We investigated the structural evolution and atomic distribution of the MLLC-templated mesoporous PtRu nanoparticles (NPs) after electroreduction for varied duration using X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) spectroscopy, complemented by energy-dispersive X-ray spectroscopy (EDS) and field-emission transmission electron microscopy (FE-TEM). The XANES data at the Ru L2,3 and Pt L3 edges show predominantly metallic states of Ru and Pt in the PtRu NPs upon electroreduction. The reduction of Ru(3+) ions in RuCl3 into Ru atoms involves intermediate RuCl-containing complexes. A more rapid reduction of Pt precursors and a release of Ru atoms from Ru precursors in two steps upon electroreduction resulted in aggregation into PtRu nanoparticles, featuring a Pt-rich core, a Ru-rich shell and a varied alloy extent of Ru, deduced from EXAFS data. The complementary results provide insight into the mechanism of growth and atomic distribution of mesostructured PtRu bimetallic nanoparticles from the use of the MLLC-type templates.

Heterogeneous junction engineering on core-shell nanocatalysts boosts the dye-sensitized solar cell.

In this study, we successfully manipulate the heterogeneous junction at Co3O4-Pt core-shell cathodic nanocatalysts (C/P CNCs) by controlling the core/shell ratios. Our results indicate the cobalt core atoms would inject their valence charge to the surface Pt atoms due to the presence of extensive lattice strain in the shell region. This charge injection accelerates the redox kinetics at the catalysts surface. Consequently, compared with that using Pt nanoparticle cathode, the C/P CNCs at an optimal Pt/Co atomic ratio of 1, improves the current density and the photovoltaic efficiency of dye-sensitized soar cell (DSSC) by ∼36.3% and ∼22.9%, respectively. By combining structure and electrochemical analysis, we systematically elucidate the effects of Pt/Co (shell/core) ratios, the interplay of Co atoms on the shell structures, and the redox activity of C/P CNCs on the DSSC performance. Hereby, this study provide mechanistic insights in developing electrocatalysts for DSSC with programmable performance and reduced Pt utilization.

Biogeochemical reductive release of soil embedded arsenate around a crater area (Guandu) in northern Taiwan using X-ray absorption near-edge spectroscopy.

This study investigates biogeochemical reductive release of arsenate from beudantite into solution in a crater area in northern Taiwan, using a combination of X-ray absorption near-edge structure (XANES) and atomic absorption spectrometry. Total arsenic (As) concentrations in the soil were more than 200 mg/kg. Over four months of laboratory experiments, less than 0.8% As was released into solution after reduction experiments. The 71% to 83% As was chemically reduced into arsenite (As(III)) and partially weathering into the soluble phase. The kinetic dissolution and re-precipitation of As, Fe, Pb and sulfate in this area of paddy soils merits further study.

Massive enhancement of photoluminescence through nanofilm dewetting.

Due to the rather low efficiencies of conjugated polymers in solid films, their successful applications are scarce. However, recently several experiments indicated that a proper control of molecular conformations and stresses acting on the polymers may provide constructive ways to boost efficiency. Here, we report an amazingly large enhancement of photoluminescence as a consequence of strong shear forces acting on the polymer chains during nanofilm dewetting. Such sheared chains exhibited an emission probability many times higher than the nonsheared chains within a nondewetted film. This increase in emission probability was accompanied by the emergence of an additional blue-shifted emission peak, suggesting reductions in conjugation length induced by the dewetting-driven mass redistribution. Intriguingly, exciton quenching on narrow-band-gap substrates was also reduced, indicating suppression of vibronic interactions of excitons. Dewetting and related shearing processes resulting in enhanced photoluminescence efficiency are compatible with existing fabrication methods of polymer-based diodes and solar cells.

Effects of Pt shell thicknesses on the atomic structure of Ru-Pt core-shell nanoparticles for methanol electrooxidation applications.

In this research, core-shell electrocatalysts comprising a Ru core covered with precisely controlled 1.5-3.6 atomic layers (ALs)-thick Pt atoms are synthesized. The sample with 1.5 ALs shows a 3.2-fold improvement in CO-tolerance and 2.4-fold current enhancement at the conventional battery operation potential (I(300), at 300 mV vs Ag/AgCl) during methanol oxidation as compared with conventional all-Pt nanoparticles. The origin of the enhanced performance and the atomic structure of the core-shell nanoparticles are elucidated to be mainly dominated by the lattice strain (possibly some slight effect of heteroatomic interactions) then by the combination of ligand effects and bifunctional mechanisms when the shell crystal is thicker than 2.7 ALs.

Neutron and X-ray scattering on the monolayer structure of a lecithin fullerene-derivative.

Using neutron reflectivity with contrast variation, X-ray reflectivity, and grazing incident small-angle X-ray scattering (GISAXS), we have characterized the in-depth and in-plane structural characteristics of the Langmuir and Langmuir-Blodgett (LB) films formed by a novel lecithin C60-derivative, FPTL, of three phospholipids jointly bonded on one single olefinic moiety of a C60 cage. Based on the neutron reflectivity measured, we have proposed a monolayer structure, with the C60 cages of FPTL lifted into the air and hydrophilic phospholipid heads immersed in water, for the FPTL Langmuir layer formed on water. On the other hand, the LB film of FPTL prepared on mica exhibits clear Kiessig fringes in the X-ray reflectivity profile, indicating a 27 angstroms monolayer film with less molecular orientation. With GISAXS, we have extracted an in-plane correlation length of about 210 A for a possible in-plane aggregation of C60 of FPTL in the LB monolayer. We have also demonstrated the highly ordered monolayer structures of a lecithin lipid, in elucidating the positive effect of the attached functional group-phospholipids on the monolayer formation of the lecithin C60-derivative.

DNA-induced aggregation of zwitterionic oligolamellar liposome.

Liposome consisting of a single zwitterionic lipid as the potential vector for gene therapy has been reported recently; however, whether polyanionic DNA can bind directly with zwitterionic lipid without the aid of multivalent salt still remains unresolved. In this study, we reveal the aggregation of zwitterionic oligolamellar liposomes composed of 1,2-di(cis-9-octadecenoyl)-sn-glycero-3-phosphocholine induced by DNA without the presence of multivalent salt. Our results demonstrate that only a small fraction (<10%) of DNA can bind electrostatically with a portion of the liposomes. Such a low degree of binding, however, induces significant aggregation of these oligolamellar liposomes, yielding large multilamellar particles in which the number of hydrophilic/hydrophobic layer stacking becomes sufficiently large to yield multiple diffraction peaks in the small-angle X-ray scattering profile. Addition of monovalent salt such as NaCl tends to disrupt the multilamellar structure.

A two-state model for the multilamellar structure of a DNA/cationic lipid complex in the bulk.

Polyanionic DNA can bind electrostatically with cationic lipids to form a complex used for gene delivery and nanostructure construction. Here, we reveal two multilamellar phases, L(I) and L(II), characterized by distinct states of lipid packing and DNA conformation in a DNA/cationic lipid complex in the bulk state. The L(II) phase, formed when the lipids are in excess of DNA in terms of overall ionic charge, is composed of B-DNA confined between the bilayers with the lipid tails aligning normal to the lamellar interface. When DNA becomes in excess of the lipids, the L(I) phase in which the DNA is bound with the tilted lipid chains adopting the A conformation is favored because this configuration offers more economical electrostatic binding between these two components.