Ternary Complex System Research Articles

Solubility Enhancement of Antidiabetic Drug Pioglitazone by using Polymer Platform Technology

A “drug delivery system” should be able to reduce toxicity and improve therapeutic benefits. The present investigation aimed to provide an approach for the solubility and bioavailability enhancement by a novel polymer platform Drug delivery system. Platform technology contains a polymeric system with a release modulator and can accommodate drugs with common physicochemical /therapeutic properties with minimal changes. Pioglitazone, BCS class II drug results in sub-therapeutic plasma drug levels which can cause failure in therapeutic response. When it comes to make PIO dissolved and soluble, microwave assisted ball milling technique was followed. Chitosan and neusiline US2 were used to prepare solid dispersion forming ternary complexation. Optimization of solid dispersion of ternary complexation, a “32 level full factorial design with Design Expert Software version 12” had been used. Pioglitazone–CH-neusiline systems helped in marked development of solubility of initial medicinal water, drug dissolution and drug stability. According to the “FTIR, DSC, and XRPD studies, PIO-CH-NS complexes could be prepared by microwave-assisted milling technology has formed stable crystalline in a ternary complex system. A novel polymer platform technique increases bioavailability, enhancing the therapeutic effect while reducing the toxicity of drug molecules with improving patient compliance.

Preparation and characterization of whey protein isolate-dextran-proanthocyanidins ternary complexes: Formation mechanism, physicochemical stability

The present study aimed to improve the stability and antioxidant properties of whey protein isolate (WPI) in food emulsion systems. A whey protein isolate-dextran (D) binary complex (GF) was prepared using wet Melad reaction. Based on this, a ternary complex (GF-PC) system of whey protein isolate-dextran-proanthocyanidins (PC) was constructed. The interaction mechanism and functional properties of this ternary system were investigated by turbidity, Fourier infrared, and fluorescence spectroscopy, as well as DPPH radical scavenging ability. Results showed that a novel ternary composite system was successfully constructed. The maximum encapsulation efficiency of PC was 93.09% when using the GF-0.4 PC complex (the mass ratio of GF to PC was 1:0.4). Turbidity, fluorescence spectroscopy, and FTIR spectroscopy analyses showed that PC was successfully encapsulated by GF and formed the ternary complex. SDS-PAGE and interaction forces showed that the noncovalent contacts increased significantly, while covalent interactions remained the main interaction between WPI, D, and PC. The GF-PC ternary complexes significantly improved emulsification properties and free radical scavenging ability compared to single WPI and GF conjugates. This study suggested that GF-PC could be used as a delivery system for functional active ingredients with enhanced emulsifying activity and antioxidant capacity.

A Preliminary Sorption Study of Uranium on MnO2 (Pyrolusite) in the Presence of Siderophore Desferrioxamine B—The Mechanism of a Ternary System

Manganese oxides have influential sorptive properties to efficiently sequester metals, such as uranium. Sorption can become complicated by metal chelating siderophores, which create a ternary system that is capable of multiple feasible mechanisms. This study analyzes the sorption behavior of desferrioxamine B (DFOB) and desferrioxamine D (DFOD) onto pyrolusite, β-MnO2, in the presence of U(VI) at pHs 6 and 8. The electrostatic adsorption performance is shown to have a 23% difference between the DFOB and DFOD surface sorption at pH 6. Inner-sphere coordination was identified through hydrolysis products of succinate and acetate. Together, these behaviors indicate a ternary complex system where both metals and ligands interact with the surface. Therefore, uranium in the environment can be attenuated by the conditions of a complex configuration involving multiple species and functional groups. This mechanism needs to be considered for any future modeling or strategies involving radionuclide remediation.

Preparation, characterization and photocatalytic properties of rare-earth ibuprofen-phenanthroline complexes

In this experiment, europium(III)-ibuprofen-phenanthroline complexes, dysprosium(III)-ibuprofen-phenanthroline complexes and terbium(III)-ibuprofen-phenanthroline complexes were prepared separately, established a ternary solid complex system, performed a series of characterization of the system, and studied the application of the rare-earth-ibuprofen-phenanthroline complex system. In the experiment, the three ternary complexes were characterized by elemental analysis, infrared analysis, ultraviolet analysis, fluorescence analysis, thermogravimetric analysis, etc., and the chemical composition of the complexes was determined, and the data and spectra obtained were analyzed. The rare-earth ternary complex was successfully prepared by a simple and feasible method. The analysis results found that the characteristics and performance of the ternary complex were enhanced, and its physical and chemical properties were explored. The successful preparation of rare earth-ibuprofen-phenanthroline ternary complexes provides a certain scientific basis and reference for the study of determining the content of ibuprofen (IBU) in vitro, and also provides a new method for the synthesis of rare-earth ternary complexes. The reason why rare-earth materials can be used as catalysts is determined by their own photoelectric characteristics. In this paper, through the experimental test of catalytic performance of IBU and different rare-earth complexes, it is found that Tb complex has the best catalytic performance, and the degradation rate of phenol can reach 64.8% in 6 h.

Facile and eco-friendly functionalization of basalt fiber with polyelectrolyte complex toward excellent interfacial adhesion of epoxy composites

In an attempt to increase the interfacial adhesion of basalt fiber/epoxy composites, a surface modification strategy by constructing ternary polyelectrolyte complex consisted of silane coupling agent-phytic acid-polyethyleneimine via dip-coating is proposed for the first time in the present work. The as-prepared functionalized basalt fiber composite exhibits markedly improved interfacial shear strength, with an average value of 81.9 ± 4.5 MPa, 75% augmentation over that of untreated basalt fiber composite. The reinforcing mechanisms are attributed to the multiple interactions of ionic cross-linked network, covalent and hydrogen bonding at interphase, also including the improved wettability and relatively rough fiber surface. Together with facile preparation approach, nature and low-cost material, the ternary polyelectrolyte complex system developed in this paper offers great potential in practical functionalization of basalt fiber, which could be hopefully extended to other high-performance fibers.

Effects of temperature and humidity on properties of ethylene/vinyl acetate‐modified ternary complex mortar

AbstractThe ternary complex system of Portland cement, aluminate cement, gypsum is suitable for the repair and strengthening of concrete structures due to its excellent characteristics, such as fast hardening, early strength, micro‐expansion, and so on. However, the application of this ternary complex was limited by the problems of low toughness and strength degradation in the late curing period. Therefore, it is meaningful to study the effects of different curing conditions on repairing materials in concrete engineering. In this paper, the actual repair environment was simulated, and the effects of different curing temperature and humidity on performances of ethylene/vinyl acetate (EVA) modified ternary complex were researched. The initial and final setting time of ternary complex increases with the increase of EVA content. And under different curing temperature and humidity, the addition of EVA improved the toughness of the ternary complex and reduced the water absorption, EVA can effectively prevent the late strength decrease of ternary complex caused by high curing temperature. Under the curing conditions of 40 and 60°C, the addition of EVA greatly improved the flexural strength and toughness of the ternary complex, low temperature environment is not suitable for EVA‐modified ternary complex.

Enhancing the water-solubility of curcuminoids-rich extract using a ternary inclusion complex system: Preparation, characterization, and anti-cancer activity

Curcuminoids are known to exert diverse pharmacological effects and used in some pharmaceutical formulations. This study describes the preparation, characterization, and enhancement in the solubility and anticancer activity of a curcuminoids-rich extract (CRE) using a ternary inclusion complex system. CRE containing 88.9% w/w curcuminoids was prepared using a ‘green’ microwave extraction coupled with fractionation on a column of hydrophobic adsorbent resin. The ternary complex consisting of CRE, hydroxylpropyl-β-cyclodextrin and polyvinylpyrrolidone K30 was prepared using the solvent evaporation method and thoroughly characterized using Fourier-transform infrared spectroscopy, powder X-ray diffractograms, differential scanning calorimetry and scanning electron microscopy. The ternary complex of CRE improved the water-solubility of curcuminoids (up to 70.3 µg/mL) as well as the dissolution rate when compared to those of CRE (0 µg/mL). In addition, the ternary complex exhibited significantly stronger anticancer activity against human lung adenocarcinoma (A-549), human cervical adenocarcinoma (HeLa) and human colon adenocarcinoma (HT-29) cell lines than CRE.

Microbial Antigen-Presenting Extracellular Vesicles Derived from Genetically Modified Tumor Cells Promote Antitumor Activity of Dendritic Cells.

Tumor-derived extracellular vesicles (EVs), as tumor vaccines, carry tumor-associated antigens (TAAs), and were expected to transfer TAAs to antigen-presenting cells. However, treatment with tumor-derived EVs exhibited no obvious antitumor effect on the established tumors, likely due to their immuno-suppressive functions, and also to the poor immunogenicity of TAAs. In order to improve the immune stimulating properties, EVs expressing a highly immunogenic bacterial antigen, 6 kDa early secretory antigenic target (ESAT-6), from Mycobacterium tuberculosis were prepared by genetically modifying the parent tumor cells with a plasmid coding for ESAT-6. Cultured B16 tumor cells were transfected with a ternary complex system consisting of pDNA, polyethylenimine (PEI), and chondroitin sulfate. The cells that were transfected with the ternary complex secreted EVs with a higher number of ESAT-6 epitopes than those transfected by a conventional DNA/PEI binary complex, due to the low cytotoxicity, and durable high expression efficiency of the ternary complex systems. The EVs presenting the ESAT-6 epitope (ESAT-EV) were collected and explored as immune modulatory agents. Dendritic cells (DCs) were differentiated from mouse bone marrow cells and incubated with ESAT-EV. After incubating with the EVs for one day, the DCs expressed a significantly higher level of DC maturation marker, CD86. The DCs treated with ESAT-EV showed a significantly improved antitumor activity in tumor-bearing mice.

Effect of mineral admixtures on the properties of grouting materials made from a ternary complex system

Novel research on the preparation of grouting materials with a high volume of mineral admixtures is presented. The grouting materials were made from a ternary complex system containing sulfoaluminate cement, aluminate cement and gypsum. The maximum contents of fly ash (FA) and ultrafine slag (UFS) in the grouting materials only containing FA or UFS were 17 wt% and 23 wt%, respectively. It was found that the incorporation of both FA and UFS greatly improved the properties of the grouts, mainly due to their composite compensation effect. The grouts containing UFS and FA in the weight ratio of 1:5, replacing 40% of the cementitious materials, showed high fluidity and the initial and 30 min fluidity values were the same (320 mm). The compressive strength at 3 d and 28 d reached 56·5 MPa and 76·4 MPa, respectively.

Computational Insights into Molecular Activation and Positive Cooperative Mechanisms of FFAR1 Modulators.

Free fatty acid receptor 1 (FFAR1), a member of class A in G-protein-coupled receptors (GPCRs), is a promising antidiabetic target. The crystal structure of FFAR1 revealed that one agonist (MK-8666) binds to the extracellular vestibule of this receptor, while another (AP8) occupies the surface pocket between transmembrane (TM) helices TM4 and TM5. In this study, we performed 1 μs unbiased molecular dynamics (MD) simulation on each of five systems, to uncover why two ligands in completely different sites both serve as agonists and how they exert a positive synergistic effect together. They are two agonist-bound systems (FFAR1_MK-8666 and FFAR1_AP8), a ternary complex system FFAR1_MK-8666_AP8, an antagonist-bound system (FFAR1_15i), and an unliganded (apo) system, among which the antagonist 15i-bound and apo systems were used as controls. The results showed that Y913.37 played a pivotal role in the activation process of FFAR1. The agonist could disrupt the Y913.37-centered residue interaction network within protein, whereas the antagonist could stabilize the network. Furthermore, our simulations revealed that the hydrophobic layer amino acid residues next to the transmission switch (CWXP) formed a gate and could open only upon agonist activation, which might exert an important role in the formation of water pathway. These results would be helpful for elucidating the molecular activation mechanism of FFAR1 and provide insights into the design and discovery of novel allosteric agonists of FFAR1 for the treatment of type 2 diabetes mellitus (T2DM).

Computer-assisted engineering of programmed drug releasing multilayer nanomedicine via indomethacin-mediated ternary complex for therapy against a multidrug resistant tumor

Nanomedicine with programmed drug release can give full play to the synergistic effect of multi-component system in complicated tumor environment. However, the construction of these programmed drug delivery systems often depends on the sophisticated materials design and synthesis. In this study, we successfully designed an indomethacin (IND)-mediated ternary complex system based on a PEG cleavable polyethyleneimine (PEI), indomethacin (IND) and benzene ring containing chemotherapeutic drugs (such as paclitaxel (PTX), doxorubicin and docetaxel). Based on the difference of hydrophobicity in these components, these components were one-pot self-assembled into drug-loaded IND mediated PEGylation cleavable nanoassemblies (IPCNs) in multilayer structure. In drug-loaded IPCNs, PEG fragments, PEI/IND, and chemotherapeutic drug were respectively distributed from the out layer to core of nanomedicine. When drug-loaded IPCNs reached tumor site through EPR effect, the PEG fragment would firstly responsively release to the acidic tumor microenvironment to expose the intermediate layer of drug-loaded IPCNs that composed by mixture of PEI and IND for increasing the surface potential to promote the uptake by tumor cells. After entering cells, IND would be released faster than chemotherapeutic drug encapsulated in core to efficiently inhibit the expression of multidrug resistance protein 1 to reverse MDR of tumor cells before chemotherapeutic drug releasing. Contributed by the staged responsively releasing of PEG fragments, IND and encapsulated chemotherapeutic drug, the drug-loaded IPCNs exhibited a superior antitumor efficacy against A549/MDR tumor cells both in vitro and in vivo. Statement of SignificanceThe way to develop programmed released drug delivery system is commonly relied on complicated material design and synthesis. Herein, under the computer-assist design, we successfully designed a ternary complex derived from indomethacin (IND), paclitaxel (PTX) and a pH-responsive PEGylated polyethyleneimine (PEG-s-PEI), and employed this ternary complex to successfully prepare a high drug loading and multilayer structured nanomedicine of PTX (PTX IPCNs). Contribute by the different location of PTX, IND and PEG-s-PEI in PTX IPCNs, PEG fragments, IND and PTX molecules could programmed release after reaching tumor for perfectly realizing the synergistic anti-tumor effect of tumor targeting, reversal of MDR and chemotherapy. Based on a fusion of these multiple mechanisms, PTX IPCNs showed a superior antitumor efficacy in mice loading A549/MDR tumor.

New lanthanide ternary complex system in electrospun nanofibers: Assembly, physico-chemical property and sensor application

The generation of novel optical sensing structures through the lanthanide coordination has been a key scientific endeavor. The design of molecular indicator for chemical response is derived from the assembly of a polymeric-based ternary europium (III) complex system (Eu(NTA)3L/PVA (NTA = 4,4,4-trifluoro-1-(naphthalen-2-yl)butane-1,3-dione, L = 2-(4-(4-(allyloxy)phenyl)-6-(pyridin-2-yl)pyridin-2-yl)pyridine, PVA = poly(vinyl acetate)). The electrospinning technique has been employed to create a nanometer scale membrane and this functional film with ultrafine fibers (diameter of about 110 nm) exhibits intense red light at 618 nm under ultra-violet excitation of 340 nm. The luminescent signal transduction involves the interaction of hydrogen chloride (HCl) with the organic ligand. The strong acidity of the analyte induces dissociation of complex network and the evolution of emission from red to blue has been observed. The fabricated nanosensor demonstrates rapid response time (<2 s) and the detection limit has been calculated to be 3.0 ppm. This effective strategy for achieving lanthanide complex-encapsulated polymer fibers will contribute to the development of new intelligent photonic devices.

Study on a Ternary Surfactant System of Disodium Hexadecyl Diphenyl Ether Disulfonate, Dodecyldimethyl Hydroxyethyl Ammonium Chloride and Fatty Alcohol Polyoxyethylene Ether

AbstractThis study was focused on a ternary complex system composed of hexadecyl diphenyl ether disulfonate (C16-MADS), dodecyl dimethyl hydroxyethyl ammonium chloride (K3) and fatty alcohol polyoxyethylene ether (AEO9). The binary mixture C-K consisting of C16-MADS and K3 was investigated and the maximum synergism was obtained when the mole ratio was 0.33:0.67. Subsequently, AEO9 was added to the binary C-K complex system to investigate whether the behavior of the new complex system, in which C-K is thought to be a surfactant, can be explained by the theory of regular solution. The maximum synergism was achieved when the molar ratio of C-K and AEO9 was 7:3. The regular solution theory could well explain the synergism in mixed micelle formation and the synergism in surface tension reduction efficiency, but the synergism in surface tension reduction effectiveness did not match with the experimental data. So, there still exist some deficiencies in the application of the regular solution theory to a complex system of three surfactants.

Influence of hydrophilic polymers addition into cinnarizine–β-cyclodextrin complexes on drug solubility, drug liberation behaviour and drug permeability

The aims of this study were (1) to prepare cinnarizine (CNZ)–β-cyclodextrin (β-CD) complexes by the kneading, co-precipitation and co-evaporation methods with (ternary system) or without (binary system) the addition of two different hydrophilic polymers [hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP)] in their two different grades (HPMC E5-LV or K4M and PVP K-25 or K-30) and (2) to determine the polymers influence on enhancing the CNZ solubility and the in vitro CNZ liberation behaviour or drug permeation characteristics via artificial membrane from the prepared CNZ–β-CD binary and ternary complexes in 0.1 N HCl (pH 1.2). The presence of hydrophilic polymers in ternary complex system did produce irregular-shaped but smooth-surfaced particles while binary complex system (with no polymer addition) did not. The ternary complexes prepared with HPMC K4M, β-CD and CNZ showed higher solubility efficiency value compared to other tested hydrophilic polymers to make ternary complex systems. Consequently, irrespective of the three preparation methods, the ternary complex systems exhibited higher drug libration behaviour in comparison to the binary complex system, physical mixtures and CNZ powder. But because of the possible presence of a solubility and permeability interplay or tradeoff particularly in the binary and ternary complex systems, the CNZ permeation amount in 0.1 N HCl (pH 1.2) via artificial membrane was established to a minimum compared to the CNZ powder. Therefore, the CNZ–β-CD complexes with or without the HPMC and PVP should unequivocally be used with great care by considering the solubility–permeability interplay or tradeoff into account.

New preparation of super-early-strength grouting materials by ternary complex system

An innovative preparation of super-early-strength grouting material made from a ternary complex system combined with a variety of admixtures is described. The ternary complex system comprised sulfoaluminate cement, aluminate cement and gypsum at respective contents of 67, 23 and 10 wt%. The effects of different retarders, the early-strength component (lithium carbonate) and superplasticisers (SP) on the setting time and strength of the ternary complex system were studied. It was found that borax had the best retarding effect and the optimum dosage was 0·4 wt%. When the dosage of the early-strength component was 0·02 wt%, the setting time and early-strength performance of the composite system conformed to requirements. In addition, the appropriate dosage of naphthalene SP for this system was determined to be 1·2 wt%. With added naphthalene SP, the initial fluidity of the composite system was increased and the 20 min fluidity loss was reduced.

Effects of mortar ratio on the properties of super early strength grouting materials by ternary complex system

An innovative research on preparation of super early strength grouts is presented. A ternary complex system of sulphoaluminate cement, aluminate cement and gypsum was used in the grouts combined with a variety of additives. The effect of mortar ratio on the properties of grouts was studied, and the microstructure was observed. The results show that high mortar ratio can prepare super early strength grouts; 2h and 90d compressive strength of the grouts is 42.6 and 105.6MPa, respectively. Furthermore, the grouting material has no retraction of late strength and possesses micro-expansion property, which attribute to the formation of ettringite.

Removal of N-compounds from diesel with a ternary complex system of six water ferric chloride/methanol/acetic acid

ABSTRACTNitrogen (N)-compounds in diesel cause a great harm to the environment as well as diesel. In this paper, N-compounds present in diesel were removed with a ternary complex denitrification system, including six water ferric chloride, methanol, and acetic acid. The factors affecting the process of removing N-compounds were investigated. The results showed that the optimum process includes six water ferric chloride to acetic acid to methanol in the ratio of 0.0667 g:2.5 mL:5 mL, the mass ratio of denitrification agents to diesel of 0.4, the reaction temperature of 35°C, the reaction time of 120 s, and the resting time of 7 min. Under the above optimum condition, the denitrification rate reached 98.38% and the recovery rate of diesel reached 96.34%; the denitrification process had a little effect on the other physico-chemical properties of diesel.

Application of Soluplus to Improve the Flowability and Dissolution of Baicalein Phospholipid Complex

In this study, a novel ternary complex system (TCS) composed of baicalein, phospholipids, and Soluplus was prepared to improve the flowability and dissolution for baicalein phospholipid complex (BPC). TCS was characterized using differential scanning calorimetry (DSC), infrared spectroscopy (IR), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The flowability, solubility, oil–water partition coefficient, in vitro dissolution, and in vivo pharmacokinetics of the system were also evaluated. DSC, IR, PXRD, and SEM data confirmed that the crystal form of baicalein disappeared in BPC and TCS. Furthermore, the angle of repose of TCS of 35° indicated an improvement in flowability, and solubility increased by approximately eight-fold in distilled water when TCS was compared with BPC (41.00 ± 4.89 μg/mL vs. 5.00 ± 0.16 μg/mL). Approximately 91.24% of TCS was released at the end of 60 min in 0.5% SDS (pH = 6.8), which suggested that TCS could improve the dissolution velocity and extent. Moreover, TCS exhibited a considerable enhancement in bioavailability with higher peak plasma concentration (25.55 μg/mL vs. 6.05 μg/mL) and increased AUC0–∞ (62.47 μg·h/mL vs. 50.48 μg·h/mL) with 123.75% relative bioavailability compared with BPC. Thus, Soluplus achieved the purpose of improving the flowability and solubility of baicalein phospholipid complexes. The application of Soluplus to phospholipid complexes has great potential.

Formulation and characterization of ternary complex of poorly soluble duloxetine hydrochloride

Duloxetine hydrochloride (DXH) suffers from poor solubility and thereby poor absorption, which ultimately leads to poor bioavailability. In present study, an attempt has been made to formulate and characterize duloxetine hydrochloride (DXH) complex, using β-cyclodextrin (β-CD) and different hydrophilic polymers in order to enhance its solubility and dissolution rate. Phase solubility study was used to investigate the interaction of the drug in binary systems (DXH-β-CD) as well as ternary systems (DXH-β-CD-hydrophilic polymer). It was observed that solubilization of DXH by β-CD was further enhanced by using HPMC K4M at 0.1% w/v concentration. Several methods were used to prepare ternary complex of DXH-β-CD-HPMC K4M. Ternary complex prepared by co-evaporation method containing DXH-β-CD-HPMC K4M in the ratio of 1:1.10:0.01 has shown the fastest dissolution rate (53.65 ± 2.83% in 5 min) as compared to pure DXH (3.03 ± 1.88% in 5 min) as well as other methods used to prepare these complexes. The prepared ternary complex system was characterized by the help of X-ray powder diffraction studies, differential scanning calorimetry and scanning electron microscopy. It was observed that enhancement in solubility as well as dissolution rate of DXH was due to formation of ternary complex system.

Maximizing gene delivery efficiencies of cationic helical polypeptides via balanced membrane penetration and cellular targeting

The application of non-viral gene delivery vectors is often accompanied with the poor correlation between transfection efficiency and the safety profiles of vectors. Vectors with high transfection efficiencies often suffer from high toxicities, making it unlikely to improve their efficiencies by increasing the DNA dosage. In the current study, we developed a ternary complex system which consisted of a highly membrane-active cationic helical polypeptide (PVBLG-8), a low-toxic, membrane-inactive cationic helical polypeptide (PVBLG-7) capable of mediating mannose receptor targeting, and DNA. The PVBLG-7 moiety notably enhanced the cellular uptake and transfection efficiency of PVBLG-8 in a variety of mannose receptor-expressing cell types (HeLa, COS-7, and Raw 264.7), while it did not compromise the membrane permeability of PVBLG-8 or bring additional cytotoxicities. Because of the simplicity and adjustability of the self-assembly approach, optimal formulations of the ternary complexes with a proper balance between membrane activity and targeting capability were easily identified in each specific cell type. The optimal ternary complexes displayed desired cell tolerability and markedly outperformed the PVBLG-8/DNA binary complexes as well as commercial reagent Lipofectamine™ 2000 in terms of transfection efficiency. This study therefore provides an effective and facile strategy to overcome the efficiency-toxicity poor correlation of non-viral vectors, which contributes insights into the design strategy of effective and safe non-viral gene delivery vectors.