Synthetic Carriers Research Articles

A Novel Anti‐Inflammatory Agent for the Management of Preeclampsia

Preeclampsia (PE) is a hypertensive disorder of pregnancy which impacts approximately 5–8% of all pregnancies worldwide and is the leading cause of maternal and fetal morbidity and mortality. PE is characterized by new onset of hypertension, typically after 20 weeks gestation, in addition to at least one other symptom such as proteinuria, liver dysfunction or low platelet count. Though the etiology of PE has yet to be elucidated, placental ischemia is believed to be central to the development of this disease. In response, the hypo‐perfused placenta releases a number of factors into the maternal circulation, including inflammatory cytokines like TNFα. Targeting this inflammatory response has been shown to lower blood pressure and improve endothelial function in preclinical PE models. We have recently developed a synthetic polypeptide drug carrier, elastic‐like polypeptide (ELP), for delivery of drugs during pregnancy. ELP prolongs the half‐life of small peptide‐based therapeutics in the circulation and prevents fetal exposure of the agents by preventing placental transfer to the fetal circulation. In order to target placental inflammation, we have produced an ELP‐ fusion protein (ELP‐P50) targeting a master regulator of inflammation, nuclear factor‐ κB (NF‐κB). Because NF‐κB has been shown to be elevated in preeclamptic women and the immune system has been shown to be activated in this disease, we tested the hypothesis that administration of ELP‐P50 would attenuate the maternal hypertension and inflammation in the reduced uterine perfusion pressure (RUPP) model of pregnancy‐induced hypertension. Compared to the sham operated rat, RUPP rats have significantly higher MAP (99 ± 4 mmHg vs 122 ± 3 mmHg; p< 0.001). Administration of ELP‐P50 from GD14–19 in RUPP rats significantly reduces MAP, at both low 50 mg/kg (122 ± 3 mmHg vs 111 ± 2 mmHg; p< 0.05) or high 75 mg/kg (122 ± 3 mmHg vs 111 ± 2 mmHg; p< 0.05) dose. As TNFα is a known target upregulated by NF‐κB, we measured the effects of ELP‐P50 on placental production of TNFα. As measured by ELISA, there was a trend for increased TNFα in RUPP animals compared to shams (4.4 ± 0.7 μg/mL/mg vs 3.2 ± 0.3 μg/mL/mg total protein; p= 0.15). When the RUPP animals were treated with the ELP‐P50, there was a significant reduction in TNFα. There was a 50% reduction in placental TNFα in both animals receiving 50 mg/kg (2.2 ± 0.3 μg/mL/mg vs 4.4 ± 0.7 μg/mL/mg total protein; p<0.05), and the animals receiving 75 mg/kg of ELP‐P50 (2.2 ± 0.1 μg/mL/mg vs 4.4 ± 0.7 μg/mL/mg total protein; p< 0.05). It is known that TNFα can also act as a cytokine to promote immune cell infiltration. For this reason, we measured T‐cell populations in the animal placentas by flow cytometry. There were no significant differences, however, in either helper T‐cells or cytotoxic T‐cells suggesting the NF‐κB activation has no impact on these resident immune cells. ELP‐P50 is able to significantly reduce blood pressure and lower levels of placental TNFα in the rodent RUPP model of placental ischemia. The fact that blood pressure is not completely returned to normal, however, unsurprisingly suggests that there are other pathways involved in the development of hypertension in the RUPP model. Future studies will further characterize the mechanism of action of this agent and confirmatory studies will be performed in other experimental models of PE to advance the translation of this agent as a possible therapeutic agent for PE.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

ELP‐VEGF Treatment Improves the Maternal Syndrome of Preeclampsia in the Dahl Salt Sensitive (S) Rat

Preeclampsia, a hypertensive disorder of pregnancy, is detrimental to both mother and fetus; however, there is currently no effective treatment for preeclampsia. The anti‐angiogenic protein sFlt‐1 has been implicated in the pathogenesis of preeclampsia through both clinical and experimental studies, leading us and others to propose that antagonism of sFlt‐1 via administration of vascular endothelial growth factor (VEGF) will reduce the maternal symptoms of hypertension and proteinuria in preeclamptic pregnancy. In this study, we tested the hypothesis that VEGF fused to the synthetic carrier elastin like polypeptide (ELP) will improve the maternal syndrome in the Dahl S rat model of superimposed preeclampsia. Female Dahl S rats (16–18 weeks of age) were placed in metabolic cages for 24‐hour urine collection, mated with Dahl S male rats, and randomly divided into control and ELP‐VEGF treated groups. ELP‐VEGF was administered via osmotic pump (5 mg/kg/day, Alzet 2ML1) beginning on day 10 of pregnancy, and pumps were replaced on day 17 of pregnancy. Urine was collected again on day 19, and blood and tissues were harvested on day 20. Urinary protein excretion (Bradford assay) did not differ between groups at baseline (87±11 vs 99±21 mg/d), but was significantly lower during late pregnancy in the ELP‐VEGF treated rats (* p=0.004, table). A subset of ELP‐VEGF‐treated rats (n=4) was implanted with telemetry transmitters (DSI) before mating. While previous studies have shown that blood pressure increases during pregnancy in the Dahl S rat, ELP‐VEGF treatment resulted in a fall in mean arterial pressure of 27±5 mmHg from day 9 to day 18 of pregnancy. No significant differences in fetal growth or litter size were observed following treatment. These data suggest that ELP‐VEGF treatment improves the maternal syndrome of preeclampsia without impairing fetal outcomes.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Analytical interference of HBOC-201 (Hemopure, a synthetic hemoglobin-based oxygen carrier) on four common clinical chemistry platforms

BackgroundThere are 13 million blood transfusions each year in the US. Limitations in the donor pool, storage capabilities, mass casualties, access in remote locations and reactivity of donors all limit the availability of transfusable blood products to patients. HBOC-201 (Hemopure®) is a second-generation glutaraldehyde-polymer of bovine hemoglobin, which can serve as an “oxygen bridge” to maintain oxygen carrying capacity while transfusion products are unavailable. Hemopure presents the advantages of extended shelf life, ambient storage, and limited reactive potential, but its extracellular location can also cause significant interference in modern laboratory analyzers similar to severe hemolysis. MethodsObserved error in 26 commonly measured analytes was determined on 4 different analytical platforms in plasma from a patient therapeutically transfused Hemopure as well as donor blood spiked with Hemopure at a level equivalent to the therapeutic loading dose (10% v/v). ResultsSignificant negative error ratios >50% of the total allowable error (>0.5tAE) were reported in 23/104 assays (22.1%), positive bias of >0.5tAE in 26/104 assays (25.0%), and acceptable bias between −0.5tAE and 0.5tAE error ratio was reported in 44/104 (42.3%). Analysis failed in the presence of Hemopure in 11/104 (10.6%). Observed error is further subdivided by platform, wavelength, dilution and reaction method. ConclusionAdministration of Hemopure (or other hemoglobin-based oxygen carriers) presents a challenge to laboratorians tasked with analyzing patient specimens. We provide laboratorians with a reference to evaluate patient samples, select optimal analytical platforms for specific analytes, and predict possible bias beyond the 4 analytical platforms included in this study.

Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy.

Extracellular vesicles (EVs) have recently gained significant attention as important mediators of intercellular communication, potential drug carriers, and disease biomarkers. These natural cell-derived nanoparticles are postulated to be biocompatible, stable under physiological conditions, and to show reduced immunogenicity as compared to other synthetic nanoparticles. Although initial clinical trials are ongoing, the use of EVs for therapeutic applications may be limited due to undesired off-target activity and potential “dilution effects” upon systemic administration which may affect their ability to reach their target tissues. To fully exploit their therapeutic potential, EVs are embedded into implantable biomaterials designed to achieve local delivery of therapeutics taking advantage of enzyme prodrug therapy (EPT). In this first application of EVs for an EPT approach, EVs are used as smart carriers for stabilizing enzymes in a hydrogel for local controlled conversion of benign prodrugs to active antiinflammatory compounds. It is shown that the natural EVs’ antiinflammatory potential is comparable or superior to synthetic carriers, in particular upon repeated long-term incubations and in different macrophage models of inflammation. Moreover, density-dependent color scanning electron microscopy imaging of EVs in a hydrogel is presented herein, an impactful tool for further understanding EVs in biological settings.

Properties of Liposomes Containing Natural and Synthetic Lipids Formed by Microfluidic Mixing

Vesicle formation by a staggered herringbone microfluidic mixer is investigated in comparison to a sonication‐extrusion method. Experiments focused on the incorporation efficiency of lipid components, on dye entrapment efficiency, and on the barrier properties of the vesicle bilayers produced. The microfluidic method produces vesicles largely under the control of thermodynamic factors. As a result, the molecular parameters of the lipids (chain length, chain volume, head group area) directly control vesicle diameter. A hydrophobic branched chain sulfonate lipid is incorporated by microfluidic mixing but not by sonication‐extrusion. The vesicles produced by microfluidic mixing can be used to study ion transport by known ionophores and appear to have directly comparable barrier properties to those produced by sonication‐extrusion. Vesicles containing the branched chain sulfonate are highly permeable. The microfluidic mixing method produces predominantly unilamellar vesicles.Practical Applications: The microfluidic device examined offers a new method to reproducibly produce vesicles that are directly controlled by the molecular components of the lipid mixture. The authors show that this method produces vesicles that are equivalent to currently used methods in the study of synthetic ion channels and carriers. Looking forward, thermodynamically controlled self‐assembly will find application in the creation of new membrane systems and assemblies where the vesicles themselves are the building blocks in more extensive structures, and the active components in inter‐vesicle functions.A staggered herringbone microfluidic mixer reproducibly gives size‐controlled unilamellar vesicles having low‐permeability bilayer membranes.

Chemical looping combustion using geopolymer-based oxygen carriers

Synthetic oxygen carriers based on geopolymer composites for chemical looping combustion have been recently proposed as alternative to traditional ones. In this work, this novel class of oxygen carriers was further developed by introducing manganese oxide (Mn2O3) as active phase. A geopolymer composite with Mn2O3 powder was produced and compared to a previously developed Fe-based system. Additionally, a mixed iron/manganese composite was fabricated to investigate possible combined effects of the two oxides. Laboratory experiments were carried out in a plant for the combustion of a CO rich gas from char gasification in CO2, consisting of two sequential fixed beds for char gasification and chemical looping combustion. The tests conducted at 900 °C pointed out the excellent performance of the Mn- and MnFe-based oxygen carriers, achieving an efficiency of CO conversion up to 99% during the first minute of operation with gas residence time less than 1 s. Moreover, the Mn-based materials exhibited the ability to release O2 during the initial stage of combustion. In the mixed iron/manganese system, the formation of the mixed phase MnFe2O4 was detected by XRD analysis, resulting in a beneficial synergistic effect. Both developed oxygen carriers (Mn- and MnFe based) exhibited similar CO conversion profiles after repeated cycles of operation.

Cell Penetrating Peptide-Based Redox-Sensitive Vaccine Delivery System for Subcutaneous Vaccination.

In immunotherapy, induction of potent cellular immunity by vaccination is essential to treat intracellular infectious diseases and tumors. In this work, we designed a new synthetic peptide carrier, Cys-Trp-Trp-Arg8-Cys-Arg8-Cys-Arg8-Cys, for vaccine delivery by integrating a redox-responsive disulfide bond cross-linking and cell-penetrating peptide arginine octamer. The carrier peptide bound to the antigen protein ovalbumin (OVA) via electrostatic self-assembly to form peptide/OVA nanocomposites. Then, the spontaneous oxidization of the thiols of the cysteine residues induced interpeptide disulfide bond cross-linking to construct denser peptide/OVA condensates. The cell-penetrating peptides incorporated in the carrier peptide could increase antigen uptake by antigen presenting cells. After being internalized by antigen presenting cells, the antigen could be rapidly released in cytoplasm along with degradation of the disulfide bonds by intracellular glutathione, which could promote potent CD8+ T cell immunity. The cross-linked peptide/OVA condensates were used for subcutaneous vaccination. The results showed that the peptide carrier mediated potent antigen-specific immune response by significantly increasing IgG titer; splenocyte proliferation; the secretion level of cytokines INF-γ, IL-12, IL-4, and IL-10; immune memory function, and the activation and maturation of dendritic cells. From the results, the low-molecular weight vaccine-condensing peptide with definite chemical composition could be developed as a novel class of vaccine delivery systems.

Immobilization of Lipase on Iron Oxide Organic/Inorganic Hybrid Particles: A Review Article

Abstract In last few decades the demand of lipase has been dramatically increase due to its useful use in numbers of biochemical industries. Varieties of natural and synthetic carriers and methodologies have been used to improve lipase activities by the process of immobilization in order to enhance its activities in term of its resistance to high temperature, pH and to increase its reusibity and storage capacity. Due to the expensive nature the recycling of the lipase has been the target of the researchers to decrease its cost in the industrial process. Magnetic iron oxide organic/inorganic hybrid nanoparticles as a support have been mostly used in the lipase immobilization due its large surface area, less toxicity, bio compatibility, easily functionalization, separation avoiding long time consuming process like filtration and centrifuging.

Strategic approaches of combined electrothermal processing of coal and carbonate mineral raw materials for obtainment of highly efficient synthetic energy carriers and non-fuel products

Coal gasification and the production of gaseous fuels include three principal directions related to the production of fuel gas: 1) composition and heat capacity of the produced gas; 2) gas generator structures; 3) characteristic properties of the obtained alternative product - low CO content and gas toxicity, which allow making full use of this gas for domestic purposes. In industrial processes of coal conversion, the following combined technologies are used most often: - semi-coking + gasification of fixed ash (low-temperature coke); - semi-coking + hydrogenation of liquid product (tar); - gasification + synthesis of high molecular weight hydrocarbons from the produced SYN gas (СО+Н) (Fischer-Tropsch synthesis). The choice of the layout for obtaining SLF (synthetic liquid fuel) can be based on specific conditions, the cost and quality of coal, energy supply, market conditions. The products obtained in the process of gasification and hydrogenation of coals pollute the atmosphere much less than the coal burned in electrical power plants. When implementing the organizational and technological model of innovative production, the first stage includes the following combined approaches for the processing of mineral raw materials and new products: 1. processing of carbonic mineral raw materials: calcium carbide, carbon dioxide (in a gaseous, liquid or solid state); 2. acetylene, plant growth regulators (PGRs), plant protection products (TAKAR). The second stage includes fuel and non-fuel products: 1. synthetic ethyl alcohol (ethanol), antifreeze, ethylene glycol, dichloroethane, synthetic drying oils, acetone, etc .; 2. carbamide (urea), ammonia, nitrogen in gaseous and liquid states, methanol, gasoline, etc.

Precise Assembly of Synthetic Carriers of siRNA through a Series of Interlocked Thermodynamically Self‐Regulated Processes

AbstractA synthetic carrier of small interfering RNA (siRNA) with customizable size, pH‐responsive degradability and optimized surface population of cell‐targeting agents is constructed precisely through a series of interlocked thermodynamically self‐regulated processes. This system consists of a unimolecular polyplex core formed from each individual molecule of networked cationic polymer and a multi‐functional shell assembled from a rationally designed triblock copolymer. The core‐forming polymer of defined size is synthesized via Zeta potential‐regulated condensation of branched and linear multi‐amine bearing oligomers through pH‐responding imidazole conjugated imine linkages. The shell‐forming copolymer consists of a multi‐carboxyl saccharide end block to guide to the surface assembly, a hydrophobic central block to form an encapsulating layer, and a poly(ethylene glycol) end block equipped with a highly selective active ester for “hooking” various cell‐targeting agents. Animal assays confirm the flexibility and convenience of this system to equip with selected functional components for systemic delivery of siRNA.

Polymer nitric oxide donors potentiate the treatment of experimental solid tumours by increasing drug accumulation in the tumour tissue

The delivery of nitric oxide (NO) specifically to solid tumours was explored in this study as a strategy to augment the passive accumulation of nanomedicines in tumours induced by the Enhanced Permeability and Retention (EPR) effect. An increase in accumulation was achieved by the binding of the chemical precursor of NO, based on an organic nitrate, to a water-soluble synthetic polymer drug carrier. Four structurally different N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer NO donors were synthesized. Depending on their chemical structure, two of these donors were hydrolytically stable, while two rapidly released the parent nitrate under acidic conditions, mimicking the intracellular environment. The polymer NO donors were shown to overcome the drawbacks related to low-molecular-weight NO releasing compounds, namely systemic toxicity, lack of site specificity, and fast blood clearance. The NO donors showed intracellular NO release upon incubation with tumour cells. In vivo, they potentiated the EPR effect, resulting in an increased accumulation of polymer-bound cytotoxic drug doxorubicin (Dox) in EL4 T-cell lymphoma inoculated in mice. This led to a better therapeutic outcome in the treatment of lymphoma with the high-molecular-weight polymer conjugates carrying Dox but not in the treatment with the free Dox. The localized augmentation of the EPR effect via the tumour-specific NO delivery system can be viewed as a promising strategy to potentiate polymer-based tumour therapy without increasing systemic toxicity.

Glycosylated Reversible Addition-Fragmentation Chain Transfer Polymers with Varying Polyethylene Glycol Linkers Produce Different Short Interfering RNA Uptake, Gene Silencing, and Toxicity Profiles.

Achieving efficient and targeted delivery of short interfering (siRNA) is an important research challenge to overcome to render highly promising siRNA therapies clinically successful. Challenges exist in designing synthetic carriers for these RNAi constructs that provide protection against serum degradation, extended blood retention times, effective cellular uptake through a variety of uptake mechanisms, endosomal escape, and efficient cargo release. These challenges have resulted in a significant body of research and led to many important findings about the chemical composition and structural layout of the delivery vector for optimal gene silencing. The challenge of targeted delivery vectors remains, and strategies to take advantage of nature's self-selective cellular uptake mechanisms for specific organ cells, such as the liver, have enabled researchers to step closer to achieving this goal. In this work, we report the design, synthesis, and biological evaluation of a novel polymeric delivery vector incorporating galactose moieties to target hepatic cells through clathrin-mediated endocytosis at asialoglycoprotein receptors. An investigation into the density of carbohydrate functionality and its distance from the polymer backbone is conducted using reversible addition-fragmentation chain transfer polymerization and postpolymerization modification.

Solid-phase supported design of carriers for therapeutic nucleic acid delivery.

Nucleic acid molecules are important therapeutic agents in the field of antisense oligonucleotide, RNA interference, and gene therapies. Since nucleic acids are not able to cross cell membranes and enter efficiently into cells on their own, the development of efficient, safe, and precise delivery systems is the crucial challenge for development of nucleic acid therapeutics. For the delivery of nucleic acids to their intracellular site of action, either the cytosol or the nucleus, several extracellular and intracellular barriers have to be overcome. Multifunctional carriers may handle the different special requirements of each barrier. The complexity of such macromolecules however poses a new hurdle in medical translation, which is the chemical production in reproducible and well-defined form. Solid-phase assisted synthesis (SPS) presents a solution for this challenge. The current review provides an overview on the design and SPS of precise sequence-defined synthetic carriers for nucleic acid cargos.

Bio-inspired engineering of cell- and virus-like nanoparticles for drug delivery.

The engineering of future generations of nanodelivery systems aims at the creation of multifunctional vectors endowed with improved circulation, enhanced targeting and responsiveness to the biological environment. Moving past purely bio-inert systems, researchers have begun to create nanoparticles capable of proactively interacting with the biology of the body. Nature offers a wide-range of sources of inspiration for the synthesis of more effective drug delivery platforms. Because the nano-bio-interface is the key driver of nanoparticle behavior and function, the modification of nanoparticles' surfaces allows the transfer of biological properties to synthetic carriers by imparting them with a biological identity. Modulation of these surface characteristics governs nanoparticle interactions with the biological barriers they encounter. Building off these observations, we provide here an overview of virus- and cell-derived biomimetic delivery systems that combine the intrinsic hallmarks of biological membranes with the delivery capabilities of synthetic carriers. We describe the features and properties of biomimetic delivery systems, recapitulating the distinctive traits and functions of viruses, exosomes, platelets, red and white blood cells. By mimicking these biological entities, we will learn how to more efficiently interact with the human body and refine our ability to negotiate with the biological barriers that impair the therapeutic efficacy of nanoparticles.

Recent progress of fully synthetic carbohydrate-based vaccine using TLR agonist as build-in adjuvant

Fully synthetic vaccine, in which one or multi-molecular antigens are conjugated to a synthetic carrier with well-defined chemical structure, is a new direction to develop carbohydrate-based vaccine against cancer and pathogens. Toll like receptor (TLR) agonists with the ability to stimulate immune response have been widely investigated and been applied as build-in adjuvants to construct fully synthetic vaccines. In particular, remarkable progress has been achieved in recent years in the development of vaccines constructed with the agonists of TLR1/2, TLR2/6 and TLR4 and tumor-associated carbohydrate antigens (TACAs). These di-, tri- or multi-component vaccine candidates showed attractive immunological properties. This review highlights recent advances in developing full synthetic carbohydrate antigen based vaccines, with an emphasis on the structure-activity relationships that provide a primary basis for future vaccine design and immunotherapy developing.

Efficient delivery of signal-responsive gene carriers for disease-specific gene expression via bubble liposomes and sonoporation

Sonoporation is a promising method to intracellularly deliver synthetic gene carriers that have lower endocytotic uptake than viral carriers. Here, we applied sonoporation to deliver genes via polyethylene glycol (PEG)-grafted polymeric carriers that specifically respond to hyperactivated protein kinase A (PKA). PEG-grafted polymeric carrier/DNA polyplexes were not efficiently delivered into cells via the endocytotic pathway because of the hydrophilic PEG layer surrounding the polyplexes. However, the delivery of polyplexes into cells was significantly increased by sonoporation. The delivered polyplexes exhibited PKA-responsive transgene expression in PKA-overexpressing cells, but not in cells with low PKA activation. These results show that the sonoporation-mediated delivery of PEG-modified PKA-responsive polyplexes is a promising approach for safely applying gene therapy to abnormal cells with hyperactivated PKA.

HPMA Copolymer-Drug Conjugates with Controlled Tumor-Specific Drug Release.

Over the past few decades, numerous polymer drug carrier systems are designed and synthesized, and their properties are evaluated. Many of these systems are based on water-soluble polymer carriers of low-molecular-weight drugs and compounds, e.g., cytostatic agents, anti-inflammatory drugs, or multidrug resistance inhibitors, all covalently bound to a carrier by a biodegradable spacer that enables controlled release of the active molecule to achieve the desired pharmacological effect. Among others, the synthetic polymer carriers based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers are some of the most promising carriers for this purpose. This review focuses on advances in the development of HPMA copolymer carriers and their conjugates with anticancer drugs, with triggered drug activation in tumor tissue and especially in tumor cells. Specifically, this review highlights the improvements in polymer drug carrier design with respect to the structure of a spacer to influence controlled drug release and activation, and its impact on the drug pharmacokinetics, enhanced tumor uptake, cellular trafficking, and in vivo antitumor activity.

Study of Antigenic Activity of Experimental Samples of the Conjugated Vaccines Based on Synthetic Oligosaccharide Ligands and CRM197 Carrier Protein against <i>Candida albicans, Aspergillus fumigatus</i> and <i>Pseudomonas aeruginosa</i>

By now there is no effective treatment for a number of socially significant bacterial and fungal diseases. β-(1→3)-glucans are the principal components of the cell wall of fungi, including Candida albicans, Aspergillusfumigatus and other. At the same time, β-(1→3)-glucans are absent in mammals and man, that makes them promising components of carbohydrate-protein conjugated vaccines for the prevention and treatment of fungal infections. Alginic acid, constructed of β-(1→ 4)-linked mannuronic acid are extracellular polysaccharides produced by Pseudomonas aeruginosa. The protein CRM197 is a non toxic derivative of diphtheria toxin, which is widely used as a safe carrier in conjugated vaccines. The purpose of this study was to investigate the antigenic activity of experimental samples of the conjugated vaccines based on synthetic oligosaccharide ligands and CRM197 carrier protein in the competitive enzyme-linked immunosorbent assay. Two-time immunization Balb/c mice with experimental samples of the conjugated vaccines induced the formation of high titers of specific antibodies. High antibody’s avidity to their oligosaccharide ligands was shown in competitive ELISA. These data suggest the relevance of further preclinical trials of the conjugated antifungal vaccine against Candida and Aspergillus and antibacterial vaccine against Pseudomonas.

Unique phase identification of trimetallic copper iron manganese oxygen carrier using simultaneous differential scanning calorimetry/thermogravimetric analysis during chemical looping combustion reactions with methane

Chemical looping combustion (CLC) is a promising combustion technology that generates heat and sequestration-ready carbon dioxide that is undiluted by nitrogen from the combustion of carbonaceous fuels with an oxygen carrier, or metal oxide. This process is highly dependent on the reactivity and stability of the oxygen carrier. Thus, the development of oxygen carriers remains one of the major barriers for commercialization of CLC. Synthetic oxygen carriers, consisting of multiple metal components, have demonstrated enhanced performance and improved CLC operation compared to single metal oxides. However, identification of the complex mixed metal oxide phases that form after calcination or during CLC reactions has been challenging. Without an understanding of the dominant metal oxide phase, it is difficult to determine reaction parameters and the oxygen carrier reduction pathway, which are necessary for CLC reactor design. This is particularly challenging for complex multi-component oxygen carriers such as copper iron manganese oxide (CuFeMnO4).This study aims to differentiate the unique phase formation of a highly reactive, complex trimetallic oxygen carrier, CuFeMnO4, from its single and bimetallic counterparts using thermochemical and reaction data obtained from simultaneous differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) during temperature programmed reductions (TPR) with methane. DSC/TGA experiments during TPR with methane provides heat flow data and corresponding reaction rate data that can be used to determine reaction routes and mechanisms during methane reduction. Furthermore, non-isothermal TPR data provides the advantage of distinguishing reactions that may not be observable in isothermal analysis.The detailed thermochemical and reaction data, obtained during TPR with methane, distinguished a unique reduction pathway for CuFeMnO4 that differed from its single and bimetallic counterparts. This is remarkable since X-ray diffraction (XRD) data alone could not be used to distinguish the reactive trimetallic oxide phase due to overlapping peaks from various single and mixed metal oxides. The unique reduction pathway of CuFeMnO4 was further characterized in this study using in-situ XRD TPR with methane to determine changes in the dominant trimetallic phase that influenced the thermochemical and reaction rate data.

Intracellular and transdermal protein delivery mediated by non-covalent interactions with a synthetic guanidine-rich molecular carrier

The impermeability of the cell plasma membrane is one of the major barriers for protein transduction into mammalian cells, and it also limits the use of proteins as therapeutic agents. Protein transduction has usually been achieved based on certain invasive processes or cell penetrating peptides (CPP). Herein we report our study in which a synthetic guanidine-rich molecular carrier is used as a delivery vector for intracellular and transdermal delivery of proteins. First a sorbitol-based molecular carrier having 8 guanidine units (Sor-G8) was synthesized, and then was simply mixed with a cargo protein of varying sizes to form the non-covalent complex of carrier-cargo proteins. These ionic complexes were shown to have efficient cellular uptake properties. The optimum conditions including the molar ratio between cargo protein and carrier, and the treatment time have been defined. Several protein cargoes were successfully examined with differing sizes and molecular weights: green fluorescent protein (MW 27kDa), albumin (66kDa), concanavalin A (102kDa), and immunoglobulin G (150kDa). These non-covalent complexes were also found to have excellent transdermal penetration ability into the mouse skin. The skin penetration depth was studied histologically by light microscopy as well as two-photon microscopy thus generating a depth profile. These complexes were largely found in the epidermis and dermis layers, i.e. down to ca. 100μm depth of the mouse skin. Our synthetic Sor-G8 carrier was found to be substantially more efficient that Arg8 in both the intracellular transduction and the transdermal delivery of proteins. The mechanism of the cellular uptake of the complex was briefly studied, and the results suggested macropinocytosis.