RESUMEN

Hydrogen sulfide has emerged as a key gasotransmitter in humans and in plants, and the addition of exogenous hydrogen sulfide has many beneficial effects in vivo and in vitro. A challenge in investigating the effect of exogenous hydrogen sulfide is tracking the location of exogenous hydrogen sulfide on an organism and cellular level. In this article, we report the synthesis of three key chemicals (cysteine trisulfide, glutathione trisulfide, and GYY-4137) that release radiolabeled 35S as hydrogen sulfide. The synthesis started with the reduction of Na235SO4 mixed with Na2SO4 to generate hydrogen sulfide gas that was trapped with aq NaOH to yield radiolabeled Na2S. The Na2S was converted in one step to GYY-4137 at 65% yield. It was also converted to bis(tributyltin) sulfide that readily reacted with N-bromophthalimide to yield a monosulfur transfer reagent. Trisulfides were synthesized by reaction with the monosulfur transfer reagent and the corresponding thiols. The levels of radioactivity of the final products could be varied on a per gram basis to alter the radioactivity for applications that require different loadings of hydrogen sulfide donors.

RESUMEN

Fatty acids (FAs) and FA methyl esters (FAMEs) are easily isolated from vegetable oil and are important starting materials for the chemical industry to produce commercial products that are green, biorenewable, and nontoxic. A challenge in these applications is that mixtures of five or more FAs and FAMEs are isolated from a vegetable oil source, and methods to separate these mixtures are decades old and have increasingly high costs associated with the production of high-purity single-component FAs or FAMEs. We developed a method to separate these mixtures using mixed matrix membranes containing nanometer-sized covalent organic frameworks. The 2D, crystalline COFs possessed narrow distributions of pore sizes of 1.3, 1.8, 2.3, and 3.4 nm that separated FAs and FAMEs based on their degrees of unsaturation. The COFs were synthesized, characterized, and then encapsulated at 10 or 20% by weight into a prepolymer of epoxy that was then fully cured. For all mixed matrix membranes, as the degree of unsaturation increased, the FAs or FAMEs had a slower flux. The largest difference in flux was obtained for a COF/epoxy membrane with a pore size of 1.8 nm, and methyl stearate had a 5.9× faster flux than methyl linolenate. These are the first membranes that can separate the important C18 FAs and FAMEs found in vegetable oil.

RESUMEN

Trisulfides and higher polysulfides are important in the body due to their function as key reservoirs of sulfane sulfur and their rapid reactions to release persulfides. Recent work has shown that persulfides act as powerful antioxidants and release hydrogen sulfide, an emerging gasotransmitter with numerous therapeutic effects. Despite the important role of polysulfides, there is a lack of understanding of their stabilities in aqueous systems. To investigate the reactivity of trisulfides and polysulfides, three key biologically important trisulfides were synthesized from cysteine, glutathione, and N-acetylcysteine, and the tetrasulfide of N-acetylcysteine was synthesized as a representative polysulfide. The stabilities of sulfides were monitored in buffered D2O using 1H NMR spectroscopy under a range of conditions including high temperatures and acidic and alkaline environments. The tri- and tetrasulfides degraded rapidly in the presence of primary and tertiary amines to the corresponding disulfide and elemental sulfur. The half-lives of N-acetylcysteine tri- and tetrasulfides in the presence of butylamine were 53 and 1.5 min, respectively. These results were important because they suggest that tri- and tetrasulfide linkages are short-lived species in vivo due to the abundance of amines in the body. Under basic conditions, cysteine and glutathione trisulfides were unstable due to the deprotonation of the ammonium group, exposing an amine; however, N-acetylcysteine trisulfide was stable at all pH values tested. Hydrogen sulfide release of each polysulfide in the presence of cysteine was quantified using a hydrogen sulfide-sensitive electrode and 1H NMR spectroscopy.

RESUMEN

The slow release of hydrogen sulfide has been shown to be beneficial to plants by protecting them from environmental stressors, increasing germination, and extending the lifetime of harvested fruits. A major challenge in this field is controlling the amount and location of release of hydrogen sulfide so that it is available for use by plants at optimal amounts. This article reports a dual method to release hydrogen sulfide near the roots of plants by controlling its release using the hydrolysis of a dithiophosphate and the degradation of poly(lactic acid) [PLA]. Di(t-butanol)dithiophosphate phenylethylamine (tBDPA) was dissolved in a solution of PLA, and the solvent was allowed to evaporate. The resulting solid was crushed in a blender and separated into microparticles with two different size distributions of 250-500 or 500-2000 µm. The microparticles were characterized by powder X-ray diffraction to measure the presence of microcrystals of tBDPA within PLA, and images obtained using scanning electron microscopy with energy dispersive X-ray analysis confirmed the presence of these crystals. Microparticles of tBDPA loaded within PLA were characterized for their release of phosphorus and hydrogen sulfide, which both showed a burst release within 3 days, followed by a steady release. Radish plants grown with microparticles of PLA loaded with tBDPA had up to a 141% increase in harvest yield compared to plants grown in the presence of free tBDPA not loaded into PLA, PLA microparticles without tBDPA, and control plants grown without PLA or tBDPA. These experiments showed that loading hydrogen sulfide-releasing chemicals into PLA is a promising method to improve the effect of hydrogen sulfide on plants.

RESUMEN

Polymerizations of phenylamines with a disulfide transfer reagent to yield poly[N,N-(phenylamino) disulfides] (poly-NADs) were investigated due to their unique repeat units that resulted in conjugation along the backbone that was perturbed by the aromatic rings and gave different colors for the polymers. These polymers were synthesized from 10 different anilines and sulfur monochloride in a step-growth polymerization. The polymers were characterized by nuclear magnetic resonance spectroscopy, size exclusion chromatography-multiangle light scattering, and UV-vis spectroscopy. These polymers possessed a polymeric backbone solely consisting of nitrogen and sulfur [-N(R)SS-], which was conjugated and yielded polymers of moderate molecular weight. Most notably, these polymers were an array of colors ranging from pale yellow to a deep purple depending on the substitution of the aromatic ring. The more electron-poor systems produced lighter yellow polymers, while the electron-rich systems gave orange, green, red, and even purple polymers.

RESUMEN

The development of chemicals to slowly release hydrogen sulfide would aid the survival of plants under environmental stressors as well as increase harvest yields. We report a series of dialkyldithiophosphates and disulfidedithiophosphates that slowly degrade to release hydrogen sulfide in the presence of water. Kinetics of the degradation of these chemicals were obtained at 85 °C and room temperature, and it was shown that the identity of the alkyl or sulfide group had a large impact on the rate of hydrolysis, and the rate constant varied by more than 104×. For example, using tert-butanol as the nucleophile yielded a dithiophosphate (8) that hydrolyzed 13,750× faster than the dithiophosphate synthesized from n-butanol (1), indicating that the rate of hydrolysis is structure-dependent. The rates of hydrolysis at 85 °C varied from a low value of 6.9 × 10-4 h-1 to a high value of 14.1 h-1. Hydrogen sulfide release in water was also quantified using a hydrogen sulfide-sensitive electrode. Corn was grown on an industrial scale and dosed with dibutyldithiophosphate to show that these dithiophosphates have potential applications in agriculture. At a loading of 2 kg per acre, a 6.4% increase in the harvest yield of corn was observed.

Asunto(s)

Sulfuro de Hidrógeno , Hidrólisis , Cinética , Sulfuros , Zea mays

RESUMEN

Heterosubstituted disulfides are an understudied class of molecules that have been used in biological studies, but they have not been investigated for their ability to release hydrogen sulfide (H2S). The synthesis of two sets of chemicals with the diaminodisulfide (NSSN) and dialkoxydisulfide (OSSO) functional groups was reported. These chemicals were synthesized from commercially available sulfur monochloride or a simple disulfur transfer reagent. Both the diaminodisulfide and dialkoxydisulfide functional groups were found to have rapid rates of H2S release in the presence of excess thiol. The release of H2S was complete with 10 min, and the only byproducts were conversion of the thiols into disulfides and the amines or alcohols originally used in the synthesis of the diaminodisulfide or dialkoxydisulfide functional groups. These results will allow the design of H2S releasing chemicals that also release natural, biocompatible alcohols or amines. Chemicals with the diaminodisulfide and dialkoxydisulfide functional groups may find applications in medicine where a controlled, burst release of H2S is needed.

RESUMEN

Leptospirosis is a global zoonosis causing significant economic losses for cattle production. Current cattle vaccines against leptospirosis need improvement to provide efficacy against multiple serovars, reduce shedding in urine, and to induce earlier and more robust immune responses. In this study, Leptospira borgpetersenii serovar Hardjo strain 203 antigen was combined with novel adjuvants (a biodegradable polyanhydride compressed rod implant (VPEAR), poly(diaminosulfide) microparticles, a water-oil-water emulsion adjuvant, and aluminum hydroxide) to develop novel vaccines. Cattle were immunized twice, at a 4 week interval, with inoculums containing adjuvants alone or leptospira antigens and immune responses were compared to responses of cattle receiving a commercial monovalent leptospirosis vaccine (Spirovac). All animals were inoculated with a single dose of Spirovac at 20 weeks to assess antigen recall responses. Serum antibody responses were increased (P > 0.05) at 8 and 20 weeks after vaccination in cattle receiving inoculums containing leptospira antigens combined with water-oil-emulsion, poly(diaminosulfide) microparticles (PNSN-MP), or aluminum hydroxide and in cattle vaccinated with Spirovac. Humoral responses were predominantly IgG1 isotypes. Antigen-specific proliferative responses were detected after initial vaccination in cattle vaccinated with Spirovac, PNSN-MP and water-oil-water treatments. Most proliferative responses occurring within CD4+ and gamma delta T cell populations expressing CD45RO and CD25 markers, a response consistent with an effector memory phenotype. Antigen-specific immune responses were not detected in cattle vaccinated with VPEAR after initial inoculation, but were detected in the antigen recall responses. PBMCs from cattle vaccinated with Spirovac, oil-water-oil, or PNSN-MP treatments had increased (P < 0.05) IL-17A release after in vitro stimulation with leptospirosis antigens, whereas all groups produced IFN-γ and IL-17A after in vitro stimulation during the antigen recall response. Our data demonstrates that combining leptospirosis antigens with these adjuvants enhances immunogenicity in cattle. Interpretative Summary: Vaccination of livestock is a key mechanism for minimizing transmission of leptospirosis, a zoonotic disease. Leptospirosis vaccines for cattle need to be improved to provide greater levels of protection from kidney colonization, better immune responses, and protection against multiple serovars. This could be accomplished using new vaccine adjuvants. In this study, several novel adjuvants were evaluated for their ability to induce effective immune responses in cattle to leptospira antigens as compared to currently available vaccines. Data suggested that vaccines containing biodegradable polymer microparticles and oil-emulsion adjuvants induced similar or greater immune responses as compared to a commercial vaccine. Our data suggest these new vaccine formulations warrant further investigation as new vaccine formulations for cattle and other livestock.

Asunto(s)

Enfermedades de los Bovinos , Leptospira , Leptospirosis , Animales , Vacunas Bacterianas , Bovinos , Enfermedades de los Bovinos/prevención & control , Leptospirosis/prevención & control , Leptospirosis/veterinaria

RESUMEN

Leptospirosis is a debilitating infectious disease that detrimentally affects both animals and humans; therefore, disease prevention has become a high priority to avoid high incidence rates of disease in the herd and break the transmission cycle to humans. Thus, there remains an important unmet need for a prophylactic vaccine that can provide long-term immunity against leptospirosis in cattle. Herein, a novel vaccine formulation was developed where poly(diaminosulfide) polymer was employed to fabricate microparticles encapsulating the antigen of Leptospira borgpetersenii serovar Hardjo strain HB15B203 (L203-PNSN). A prime-boost vaccination with a L203-PNSN microparticle formulation increased the population of L203-specific CD3+ T cells and CD21+ B cells to levels that were significantly higher than those of cattle vaccinated with L203-AlOH or the vehicle control (empty PNSN microparticles and blank AlOH). In addition, L203-PNSN was demonstrated to stimulate durable humoral immune responses as evidenced by the increases in the antibody serum titers following the vaccination. It was also found that cattle vaccinated with L203-PNSN produced higher macroscopic agglutinating titers than cattle in other groups. Thus, it can be concluded that L203-PNSN is a novel first-in-class microparticle-based Leptospira vaccine that represents a powerful platform with the potential to serve as a prophylactic vaccine against leptospiral infection in cattle.

Asunto(s)

Antígenos Bacterianos/administración & dosificación , Vacunas Bacterianas/administración & dosificación , Leptospira/inmunología , Leptospirosis/prevención & control , Microplásticos/química , Animales , Vacunas Bacterianas/inmunología , Bovinos , Enfermedades de los Bovinos/microbiología , Enfermedades de los Bovinos/prevención & control , Sistemas de Liberación de Medicamentos/métodos , Ensayo de Inmunoadsorción Enzimática , Inmunidad Humoral , Inmunización Secundaria , Leptospirosis/inmunología , Leptospirosis/veterinaria , Masculino , Microplásticos/síntesis química , Polímeros/química , Linfocitos T/inmunología

RESUMEN

Hydrogen sulfide is a key gasotransmitter for plants and has been shown to greatly increase their growth and survival in the presence of environmental stressors. Current methods for slowly releasing hydrogen sulfide use chemicals, such as GYY-4137, but these result in the release of chemicals not found in the environment, and chemicals used may lack structures that can be readily tuned to affect the rate of release of hydrogen sulfide. In this article, we describe the synthesis and slow release of hydrogen sulfide from dialkyldithiophosphates, which are a new set of hydrogen sulfide releasing chemicals that can be used in agriculture. The rates of hydrolysis of dibutyldithiophosphate and GYY-4137 were measured in water at 85 °C and compared with each other to investigate their differences. GYY-4137 is widely used as a chemical that slowly releases H2S, but its rate of release was not previously quantified. The release of hydrogen sulfide in water at room temperature was measured for a series of dialkyldithiophosphates using a hydrogen sulfide electrode. It was shown that the structure of the dialkyldithiophosphate affected the amount of hydrogen sulfide released. The final degradation products of dibutyldithiophosphate were shown to be phosphoric acid and butanol, which are chemicals found in the environment. This result was notable because it demonstrated that dialkyldithiophosphates degrade to safe, natural chemicals that will not pollute the environment. To demonstrate that dialkyldithiophosphates have potential applications in agriculture, maize was grown for 4.5 weeks after exposure to 1-200 mg of dibutyldithiophosphate, and the weight of corn plants increased by up to 39% at low loadings of dibutyldithiophosphate.

Asunto(s)

Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacología , Sulfuro de Hidrógeno/química , Sulfuro de Hidrógeno/farmacología , Organotiofosfatos/química , Zea mays/efectos de los fármacos , Portadores de Fármacos/química , Composición de Medicamentos/métodos , Hidrólisis , Morfolinas/química , Compuestos Organotiofosforados/química , Zea mays/crecimiento & desarrollo

RESUMEN

Hydrogen sulfide (H2S) has emerged as a gaseous mediator capable of exhibiting many beneficial properties including cytoprotection, anti-inflammation, and vasodilation. The study presented here provides characterization of a poly(lactic acid) polymer with a functionalized 4-hydroxythiobenzamide (PLA-4HTB) capable of extended H2S release. The polymer was used to fabricate microparticles that can be potentially loaded with a drug allowing for co-release of the drug and H2S. Microparticles with the average diameter of 500 ± 207 nm were fabricated and shown to release 77.0 ± 1.76 µM of H2S over 4 weeks (release of H2S from 1 mg of particles). To test for the antioxidant properties of the PLA-4HTB microparticles, human embryonic kidney 293 cells were first incubated with PLA-4HTB microparticles and then oxidative stress was induced using CoCl2. Particle suspensions of 1 mg/mL were shown to protect cells resulting in reactive oxygen species (ROS) levels of superoxide that were similar to that of the control group. The microparticles fabricated from the PLA-4HTB released H2S over a sustained period of weeks to months, while providing protection from ROS. The microparticles described in this article represent a new platform technology that could be used to prevent and treat diseases caused by oxidative damage.

Asunto(s)

Benzamidas/química , Portadores de Fármacos/química , Sulfuro de Hidrógeno/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Poliésteres/química , Preparaciones de Acción Retardada , Células HEK293 , Humanos

RESUMEN

Hydrogen sulfide (H2S) is a key gasotransmitter in agriculture and has been reported to increase the growth of plants in the first two weeks and to mitigate the effects of environmental stressors. GYY-4137 is widely used in these studies because it slowly releases H2S, but there is disagreement as to whether it requires enzymes to release H2S. In this article we describe the release of H2S in water without enzymes and that it releases H2S faster in organic solvents than in water or when mixed in topsoil. Furthermore, we describe the long-term effect of dosing pea, radish, and lettuce plants with GYY-4137 for up to six weeks. The effect of GYY-4137 on plant growth for six weeks was either positive or negative depending on the loading of GYY-4137 and how it was applied to plants. The addition of GYY-4137 to lettuce plants via potting mix resulted in reduced growth and death of the plants. In contrast, application of GYY-4137 to the leaves of lettuce plants increased the harvest weight of the leaves by up to 86%. Our results demonstrate that GYY-4137 can have a positive, important effect on the growth of plants but that this effect is dependent on several factors.

Asunto(s)

Sulfuro de Hidrógeno , Lactuca/crecimiento & desarrollo , Morfolinas , Compuestos Organotiofosforados , Pisum sativum/crecimiento & desarrollo , Raphanus/crecimiento & desarrollo , Sulfuro de Hidrógeno/química , Hidrólisis , Morfolinas/química , Compuestos Organotiofosforados/química , Agua/química

RESUMEN

This article reports the fabrication of organic solvent nanofiltration membranes containing a labile disulfide bond, which is broken by reaction with a chemical stimulus. These membranes are a new generation of smart membranes that have tailored selectivities and flux that can be altered by reacting with a chemical stimulus. The selectivity and flux of chemicals through the membranes was controlled by varying the concentration of disulfide bonds in the membrane. When the disulfide bonds were cleaved, the pores in the membrane became larger and yielded different separation properties. The membrane selectivity was changed by up to 70% and flux was increased up to 5×. The rapid change in selectivity of the membrane allowed for the separation of three-component mixtures. A three-component mixture of 33.3% m-dinitrobenzene, 33.3% triphenylmethane, and 33.3% 1,3,5-tris(diphenylamino)benzene (TDAB) was separated into three different fractions that were significantly enriched in one of the three molecules. The first fraction contained m-dinitrobenzene at 82% purity and 84% yield, the second fraction contained triphenylmethane at 67% purity and 49% yield, and the third fraction contained TDAB at 71% purity and 88% yield.

RESUMEN

Epoxy nanofiltration membranes were fabricated by the step polymerization of a primary diamine and a diepoxide or triepoxide conomomer. Membrane selectivity and flux were tuned by changing the identity of the diepoxides and by increasing the concentration of triepoxides in the polymerization. The membranes were used to separate even chain length saturated fatty acids (FAs) and saturated fatty acid methyl esters (FAMEs) that possessed molecular weights between 80 - 300 g mol-1. Our membranes show excellent selectivities of up to 100:1 for the separation of the C4-C18 FAMEs. The flux of the FAMEs through the membranes showed an exponential dependence based on the number of carbons. Fabrication of thin epoxy membranes with thicknesses of 150 nm allowed for an increase in flux of FAMEs through the membrane and demonstrated that these separations can be used under industrially relevant conditions.

RESUMEN

Membrane separations are highly desired for the chemical industry because they are inexpensive, avoid the use of heat, can be applied to the purification of a wide range of chemicals, and can be scaled to industrial levels. Separating chemicals with molecular weights between 100 and 300 g mol(-1) remains a significant challenge in the field of organic solvent nanofiltration (OSN) due to their similar sizes and rotational flexibility. In this work, we report the fabrication of poly(epoxy) membranes that show excellent selectivity of over 100:1 for chemicals in this range. The membranes are easily tuned to obtain different flux and selectivity by using interchangeable amine and epoxide monomers. These membranes were used to separate the important nutritional omega-3 fatty acid ethyl esters eicosapentaenoic ethyl ester (EPA-EE) and docosahexaenoic acid ethyl ester (DHA-EE) from each other, despite a small difference in molecular weight (26 g mol(-1)). This is the first example of a separation of EPA-EE and DHA-EE using a membrane process.

RESUMEN

The aim of the research presented here was to determine the characteristics and immunostimulatory capacity, in vivo, of antigen and adjuvant co-loaded into microparticles made from a novel diaminosulfide polymer, poly(4,4'-trimethylenedipiperdyl sulfide) (PNSN), and to assess their potential as cancer vaccine vectors. PNSN microparticles co-loaded with the antigen, ovalbumin (OVA), and adjuvant, CpG 1826, (PNSN(OVA + CpG)) were fabricated and characterized for size (1.64 µm diameter; PDI=0.62), charge (-23.1 ± 0.3), and loading efficiencies of antigen (7.32 µg/mg particles) and adjuvant (0.95 µg/mg particles). The ability of PNSN(OVA + CpG) to stimulate cellular and humoral immune responses in vivo was compared with other PNSN microparticle formulations as well as with poly(lactic-co-glycolic acid)(PLGA)-based microparticles, co-loaded with OVA and CpG (PLGA(OVA + CpG)), an adenovirus encoding OVA (Ad5-OVA), and OVA delivered with incomplete Freund's adjuvant (IFA(OVA)). In vivo OVA-specific IgG1 responses, after subcutaneous prime/boosts in mice, were similar when PNSN(OVA + CpG) and PLGA(OVA + CpG) were compared and the presence of CpG 1826 within the PNSN microparticles demonstrated significantly improved responses when compared to PNSN microparticles loaded with OVA alone (PNSN(OVA)), plus or minus soluble CpG 1826. Cellular immune responses to all particle-based vaccine formulations ranged from being negligible to modest with PNSN(OVA + CpG) generating the greatest responses, displaying significantly increased levels of OVA-specific CD8+ T lymphocytes compared to controls and IFA(OVA) treated mice. Finally, it was shown that of all vaccination formulations tested PNSN(OVA + CpG) was the most protective against subsequent challenge with an OVA-expressing tumor cell line, E.G7. Thus, microparticles made from poly(diaminosulfide)-based macromolecules possess promising potential as vaccine vectors and, as demonstrated here, may have impact as cancer vaccines in particular.

Asunto(s)

Adyuvantes Inmunológicos/administración & dosificación , Vacunas contra el Cáncer/administración & dosificación , Portadores de Fármacos , Oligodesoxirribonucleótidos/administración & dosificación , Ovalbúmina/administración & dosificación , Polímeros/química , Sulfuros/química , Timoma/tratamiento farmacológico , Neoplasias del Timo/tratamiento farmacológico , Adyuvantes Inmunológicos/química , Animales , Vacunas contra el Cáncer/química , Vacunas contra el Cáncer/inmunología , Línea Celular Tumoral , Química Farmacéutica , Adyuvante de Freund/administración & dosificación , Inmunidad Celular/efectos de los fármacos , Inmunidad Humoral/efectos de los fármacos , Ácido Láctico/química , Masculino , Ratones Endogámicos C57BL , Oligodesoxirribonucleótidos/química , Oligodesoxirribonucleótidos/inmunología , Ovalbúmina/química , Ovalbúmina/genética , Ovalbúmina/inmunología , Tamaño de la Partícula , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Timoma/genética , Timoma/inmunología , Timoma/patología , Neoplasias del Timo/genética , Neoplasias del Timo/inmunología , Neoplasias del Timo/patología , Factores de Tiempo , Transfección , Carga Tumoral/efectos de los fármacos , Vacunación

RESUMEN

Hydrogen sulfide is emerging as a critically important molecule in medicine, yet there are few methods for the long-term delivery of molecules that degrade to release H2S. In this paper the first long-term release of a thiobenzamide that degrades to release H2S is described. A series of polymers were synthesized by the copolymerization of L-lactide and a lactide functionalized with 4-hydroxythiobenzamide. A new method to attach functional groups to a derivative of L-lactide is described based on the addition of a thiol to an α,ß-unsaturated lactide using catalytic I2. This reaction proceeded under mild conditions and did not ring-open the lactone. The copolymers had molecular weights from 8 to 88 kg mol-1 with PDIs below 1.50. Two sets of microparticles were fabricated from a copolymer; the average diameters of the microparticles were 0.53 and 12 µm. The degradation of the smaller microparticles was investigated in buffered water to demonstrate the slow release of thiobenzamide over 4 weeks. Based on the ability to synthesize polymers with different loadings of thiobenzamide and that thiobenzamide is a known precursor to H2S, these particles provide a polymer-based method to deliver H2S over days to weeks.

RESUMEN

Polysulfenamides (PSN), with a SN linkage (RSNR2) along the polymer backbone, are a new class of biodegradable and biocompatible polymers. These polymers were unknown prior to 2012 when their synthesis and medicinally relevant properties were reported. The aim of this study was to develop microparticles as a controlled drug delivery system using polysulfenamide as the matrix material. The microparticles were prepared by a water-in-oil-in-water double-emulsion solvent-evaporation method. For producing drug-loaded particles, FITC-dextran was used as a model hydrophilic compound. At the optimal formulation conditions, the external morphology of the PSN microparticles was examined by scanning electron microscopy to show the formation of smooth-surfaced spherical particles with low polydispersity. The microparticles had a net negative surface charge (-23 mV) as analyzed by the zetasizer. The drug encapsulation efficiency of the particles and the drug loading were found to be dependent on the drug molecular weight, amount of FITC-dextran used in fabricating FITC-dextran-loaded microparticles, concentration of PSN and surfactant, and volume of the internal and external water phases. FITC-dextran was found to be distributed throughout the PSN microparticles and was released in an initial burst followed by more continuous release over time. Confocal laser scanning microscopy was used to qualitatively observe the cellular uptake of PSN microparticles and indicated localization of the particles in both the cytoplasm and the nucleus.

Asunto(s)

Polímeros/química , Sulfamerazina/química , Cápsulas/química , Cápsulas/farmacología , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacología , Emulsiones/química , Emulsiones/farmacología , Células HEK293 , Humanos , Polímeros/farmacología , Sulfamerazina/farmacología

RESUMEN

This article describes the separation of mixtures of fatty acid salts using a new organic solvent nanofiltration membrane based on polydicyclopentadiene (PDCPD). Mixtures of free fatty acids could not be separated by the membranes because they permeated at similar rates. When triisobutylamine was added to the fatty acids, the cis-fatty acid salts (oleic, petroselinic, vaccenic, linoleic, and linolenic acid) had slower permeation though the membranes than saturated (stearic acid) and trans-fatty acid (elaidic acid) salts. The reason for the difference in permeation was due to the formation of stable salt pairs between the amine and fatty acids that increased their cross-sectional areas. The fatty acid salts derived from saturated and trans-fatty acids were smaller than the critical area cutoff for the PDCPD membranes, so they readily permeated. In contrast, the fatty acid salts derived from the cis-fatty acids had critical areas larger than critical area cutoff of the PDPCD membranes and had slowed permeation. The partitioning coefficients of fatty acids and fatty acid salts were investigated to demonstrate that they were not responsible for the difference in permeation. The use of pressure was investigated to greatly accelerate the permeation through the membranes. For a solvent mixture of 35/65 (v/v) toluene/hexanes, the permeation of solvent was approximately 39 L m(-2) h(-1). This value is similar to values reported for permeation through membranes used in industry. The separation of a mixture of fatty acids based on the composition of soybean oil was investigated using pressure. The saturated fatty acid salts were almost completely removed from the cis-fatty acid salts when iBu(3)N was used as the amine to form the salt pairs. The separation of the cis-fatty acids found in soybean oil was investigated with Pr(3)N as the amine. The oleic acid salt (oleic acid has one cis double bond) preferentially permeated the membrane while the linoleic (two cis double bonds) and linolenic (three cis double bonds) salts were partly retained. The separation of fatty acids using membranes may have real applications in industry to purify fatty acids on a large scale.

Asunto(s)

Ácidos Grasos/química , Ácidos Grasos/aislamiento & purificación , Filtración/instrumentación , Polímeros/química , Filtración/métodos , Indenos/química , Membranas Artificiales , Nanopartículas/química , Polímeros/síntesis química , Porosidad , Ácidos Grasos trans/aislamiento & purificación

RESUMEN

Although numerous small molecules have been synthesized with sulfenamide bonds (R(2)N-SR), this is the first report of the synthesis of polysulfenamides. These polymers are readily synthesized at room temperature using secondary diamines and dithiosuccinimides. The dithiosuccinimides were readily synthesized in one step by the reaction of dithiols such as HS(CH(2))(6)SH with N-chlorosuccinimide. The resulting dithiosuccinimides were either recrystallized or readily purified by chromatography on silica gel and required no special handling. The conversions of polymerization ranged from 95 to 98%, and the molecular weights of the polymer reached as high as 6,300 g mol(-1). The sulfenamide bond was very stable in organic solvents, and no degradation was observed under atmospheric conditions in C(6)D(6) for 30 days. In contrast, the sulfenamide bond readily decomposed in less than 12 h in D(2)O. Polysulfenamides were fabricated into micron-sized particles loaded with dye and endocytosed into JAWSII immature dendritic and HEK293 cells. Polysulfenamides represent a new class of polymers that are readily synthesized, stable in aprotic solvents, and readily degrade in water.