RESUMEN
Vitamin C (VC)-loaded oleogel (VCOG) with corn oil and monoglyceride stearate was used to replace lipid phase of margarine completely. The oxidative stability of VCOG was evaluated at 60±1°C in a lightproof oven for 18 days and the result showed that VCOG peroxide (> 6 days) and p-anisidine value (> 4 days) was significantly lower than that of bulk oil and VC-free oleogel (p < 0.05). Then, the margarine containing 79.70% VCOG (VCOGM) was in comparison with four commercial butter in sensory and physical characteristic. Results showed that firmness, solid fat content and trans fatty acid of VCOGM were in the lowest values while unsaturated fatty acid and adhesiveness of VCOGM was in the highest values. Furthermore, VCOGM presented the similar springiness, cohesiveness, gumminess, score appearance, texture, taste and overall impression to some/all commercial butters selected in this research (p > 0.05). These results implied that VC-loaded oleogel was an excellent alternative of lipid phase in margarine which confirmed by 55% "definitely buy" and 25% "try once-then decide".
Asunto(s)
Ácido Ascórbico/química , Aceite de Maíz/química , Ácidos Grasos Insaturados/química , Margarina , Monoglicéridos/química , Estearatos/química , Mantequilla , Comportamiento del Consumidor , Ácidos Grasos Insaturados/análisis , Humanos , Compuestos Orgánicos/química , Oxidación-Reducción , Gusto , Triglicéridos/análisis , Triglicéridos/químicaRESUMEN
In this paper, different types of oleogels were prepared by five gelators including hydroxypropyl methyl cellulose (HPMC), monoacylglycerol (MAG), sodium stearyl lactate (SSL), rice bran wax (RBW) and beeswax (BW), and their applications in cookies were compared. Texture, microstructure, and colour results showed that MAG, RBW and shortening based cookies had similar hardness, porous structure, and L*, a*, b*. MAG and RBW exhibited excellent rheological properties similar to shortening. Regarding the consumer sensory evaluation of cookies, RBW, MAG and shortening had similar scores of 3.9, 4.3 and 4.1, respectively. For wax-based oleogels, the higher the content of ß' crystal and solid fat content (SFC), the lower the hardness of cookies, but the cookies hardness of emulsifier based oleogels do not depend on ß' content and SFC. This paper confirmed the best gelators for cookies, and provided a reference for developing the oleogels to match the quality of shortening in cookies.
Asunto(s)
Dulces/análisis , Rastreo Diferencial de Calorimetría , Culinaria/métodos , Dureza , Derivados de la Hipromelosa/química , Monoglicéridos/química , Compuestos Orgánicos/química , Reología , Estearatos/química , Ceras/químicaRESUMEN
For efficient intranasal transport of parathyroid hormone (1-34) [PTH(1-34)], there is a great medical need to investigate permeation enhancers for intranasal formulations. In this study, the development of PTH(1-34) intranasal formulations was conducted. Based on conformation and chemical stability studies, the most preferable aqueous environment was determined to be 0.008 M acetate buffer solution (ABS). Subsequently, citric acid and Kolliphor® HS·15 were compared as permeation enhancers. The mechanisms of action of citric acid and Kolliphor® HS·15 were investigated using an in vitro model of nasal mucosa, and Kolliphor® HS·15 led to higher permeability of fluorescein isothiocyanate-labeled PTH(1-34) (FITC-PTH) by enhancing both the transcellular and paracellular routes. Moreover, citric acid showed severe mucosal toxicity resulting in cilia shedding, while Kolliphor® HS·15 did not cause obvious mucosa damage. Finally, Kolliphor® HS·15 was studied as a permeation enhancer using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The results showed that 5% and 10% Kolliphor® HS·15 increased the bioavailability of PTH(1-34) to 14.76% and 30.87%, respectively. In conclusion, an effective and biosafe PTH(1-34) intranasal formulation was developed by using 10% Kolliphor® HS·15 as a permeation enhancer. Intranasal formulations with higher concentrations of Kolliphor® HS·15 for higher bioavailability of PTH(1-34) could be further researched.
Asunto(s)
Excipientes/química , Mucosa Nasal/metabolismo , Hormona Paratiroidea/administración & dosificación , Administración Intranasal , Animales , Anuros , Disponibilidad Biológica , Cromatografía Liquida , Ácido Cítrico/química , Ácido Cítrico/toxicidad , Excipientes/toxicidad , Femenino , Masculino , Hormona Paratiroidea/farmacocinética , Hormona Paratiroidea/toxicidad , Permeabilidad , Polietilenglicoles/química , Polietilenglicoles/toxicidad , Ratas , Ratas Sprague-Dawley , Estearatos/química , Estearatos/toxicidad , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) that can effectively control the pain and inflammation caused by rheumatoid arthritis (RA), but its usage is limited due to severe adverse effects. For this reason, making more specific formulations of this drug can be considered. The aim of the present study was designing a novel nano-sized indomethacin delivery system. MATERIALS AND METHODS: Indomethacin-loaded dextran stearate polymeric micelles were prepared by dialysis method. Particle size and zeta potential of micelles were measured by a zeta sizer instrument. Drug release from micelles was investigated in phosphate buffer medium pH 7.4 and then the best formulation regarding physical properties and drug release was selected for animal studies. Arthritis was induced by complete Freund's adjuvant injection in rats. Then, the animals were randomly assigned into the model, the indomethacin solution and the polymeric micelles groups. The clinical effects of polymeric micelle formulation were assessed by measuring arthritis index, animal paw edema and measuring biochemical parameters including myeloperoxidase (MPO) activity, lipid peroxidation (LPO), glutathione (GSH), total antioxidant capacity (TAC), TNF-α, IL-17 and IL-1ß. RESULTS: Paw edema was attenuated following the administration of indomethacin-loaded polymeric micelles. Based on the findings of the present study, the use of indomethacin-loaded polymeric micelles could improve inflammatory symptoms, decrease arthritis index and decrease the diameter of the paw in arthritic rats in a significant manner (p ≤ 0.05). In addition, the use of polymeric micelles like indomethacin solution significantly reduced (p ≤ 0.05) the activity of MPO, LPO, TNF-α, IL-17 and IL-1ß, and made a significant increase (p ≤ 0.05) in glutathione and TAC content and ameliorated structural changes in the paw tissue compared to the control group. CONCLUSION: Our findings demonstrated that indomethacin-loaded dextran stearate polymeric micelles can provide more effective therapeutic effects in control of inflammation in arthritis in rat.
Asunto(s)
Artritis Experimental/tratamiento farmacológico , Dextranos/química , Sistemas de Liberación de Medicamentos , Indometacina/farmacología , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacología , Artritis Experimental/fisiopatología , Liberación de Fármacos , Edema/tratamiento farmacológico , Edema/patología , Adyuvante de Freund , Indometacina/administración & dosificación , Inflamación/tratamiento farmacológico , Inflamación/patología , Masculino , Micelas , Polímeros/química , Ratas , Ratas Wistar , Estearatos/químicaRESUMEN
In the present work, polybutylene succinate (PBS)/stearate modified magnesium-aluminium layered double hydroxide (St-Mg-Al LDH) composites were prepared via melt processing and the effect of different loadings of St-Mg-Al LDH on the degradation behaviour of PBS under marine conditions was investigated. The morphological, mechanical and thermal characteristics of the composites were studied using different characterisation techniques. Optical imaging and scanning electron microscopy revealed that the incorporation of St-Mg-Al LDH accelerates the degradation of PBS along with the activity of microorganisms adhered to the composite films. PBS/St-Mg-Al LDH composites are found to have lower thermal degradation temperatures than those of pure PBS. The decrease in thermal stability is correlated with the degradation of PBS due to the catalytic action Mg and Al present in LDH. Tensile and DMA analysis revealed that the addition of St-Mg-Al LDH did not have a significant impact on the mechanical properties of PBS.
Asunto(s)
Alquenos/química , Aluminio/química , Biodegradación Ambiental , Hidróxidos/química , Magnesio/química , Nanocompuestos/química , Estearatos/química , Succinatos/química , Fenómenos Químicos , Fenómenos Mecánicos , Océanos y Mares , Polímeros , Análisis EspectralRESUMEN
The 2-ethylhexyl stearate is used as a bio-lubricant in various cosmetic products. The present study is focused on the biocatalyzed esterification of 2-ethylhexanol and stearic acid to form 2-ethylhexyl stearate catalyzed by Fermase CALB 10000 in the presence of ultrasound treatment. The maximum conversion (95.87%) was obtained at molar ratio of 2-ethylhexanol to stearic acid 2:1, enzyme amount of 2 % (w/w), power 80 W, duty cycle 50 % and temperature 50°C in comparatively short reaction time (3 h) in the presence of Fermase as a catalyst. At optimum conditions, it is observed that in the presence of ultrasound; the reaction time minimizes up to 4 h as compared to mechanical stirring method (7 h). The physiochemical properties for the 2-ethylhexyl palmitate were also evaluated.
Asunto(s)
Hexanoles/química , Estearatos/síntesis química , Ondas Ultrasónicas , Biocatálisis , Fenómenos Químicos , Enzimas Inmovilizadas/química , Esterificación , Estearatos/química , Ácidos Esteáricos/química , Temperatura , Factores de TiempoRESUMEN
BACKGROUND: Doxorubicin (DOX) is a leading chemotherapeutic in cancer treatment because of its high potency and broad spectrum. Liposomal doxorubicin (Doxil®) is the first FDA-approved PEG-liposomes of DOX for the treatment of over 600,000 cancer patients, and it can overcome doxorubicin-induced cardiomyopathy and other side effects and prolong life span. The addition of MPEG2000-DSPE could elevate the total cost of cancer treatment. OBJECTIVE: We intended to prepare a novel DOX liposome that was prepared with inexpensive materials egg yolk lecithin and Kolliphor HS15, thus allowing it to be much cheaper for clinical application. METHODS: DOX liposomes were prepared using the combination of thin-film dispersion ultrasonic method and ammonium sulfate gradient method and the factors that influenced formulation quality were optimized. After formulation, particle size, entrapment efficiency, drug loading, stability, and pharmacokinetics were determined. RESULTS: DOX liposomes were near-spherical morphology with the average size of 90 nm and polydispersity index (PDI) of less than 0.30. The drug loading was up to 7.5%, and the entrapment efficiency was over 80%. The pharmacokinetic studies showed that free DOX could be easily removed and the blood concentration of free DOX group was significantly lower than that of DOX liposomes, which indicated that the novel DOX liposome had a certain sustainedrelease effect. CONCLUSION: In summary, DOX liposome is economical and easy-prepared with prolonged circulation time. Lay Summary: Doxorubicin (DOX) is a leading chemotherapeutic in cancer treatment because of its high potency and broad spectrum. Liposomal doxorubicin (Doxil®) is the first FDAapproved PEG-liposomes of DOX to treat over 600.000 cancer patients, overcoming doxorubicin- induced cardiomyopathy and other side effects and prolonging life span. The addition of MPEG2000-DSPE could elevate the total cost of cancer treatment. We intend to prepare a novel DOX liposome prepared with inexpensive materials egg yolk lecithin and Kolliphor HS15, thus allowing it to be much cheaper for clinical use. The novel DOX liposome is economical and easy-prepared with prolonged circulation time.
Asunto(s)
Antibióticos Antineoplásicos/farmacocinética , Doxorrubicina/análogos & derivados , Lecitinas/química , Polietilenglicoles/química , Estearatos/química , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/sangre , Antibióticos Antineoplásicos/química , Preparaciones de Acción Retardada , Doxorrubicina/administración & dosificación , Doxorrubicina/sangre , Doxorrubicina/química , Doxorrubicina/farmacocinética , Composición de Medicamentos , Liberación de Fármacos , Estabilidad de Medicamentos , Inyecciones Intravenosas , Liposomas , Masculino , Tamaño de la Partícula , Polietilenglicoles/administración & dosificación , Polietilenglicoles/farmacocinética , Ratas Sprague-Dawley , Tecnología FarmacéuticaRESUMEN
The dietary intake of elaidate (elaidic acid), a trans-fatty acid, is associated with the development of various diseases. Since elaidate is a C18 unsaturated fatty acid with a steric structure similar to that of a C18 saturated fatty acid (stearate), we previously revealed that insulin-dependent glucose uptake was impaired in adipocytes exposed to elaidate prior to and during differentiation similar to stearate. However, it is still unknown whether the mechanism of impairment of insulin-dependent glucose uptake due to elaidate is similar to that of stearate. Here, we indicate that persistent exposure to elaidate has particular effects on insulin signaling and GLUT4 dynamics. Insulin-induced accumulation of Akt at the plasma membrane (PM) and elevations of phosphorylated Akt and AS160 levels in whole cells were suppressed in adipocytes persistently exposed to 50 µM elaidate. Interestingly, persistent exposure to the same concentration of stearate has no effect on the phosphorylated Akt and AS160 levels. When cells were exposed to these fatty acids, elaidate suppressed insulin-induced fusion, but not translocation, of GLUT4 storage vesicles in the PM, whereas stearate did not suppress the fusion and translocation of GLUT4 storage, indicating that elaidate has suppressive effects on the accumulation of Akt and fusion of GLUT4 storage vesicles and that both elaidate and stearate vary in the mechanisms by which they impair insulin-dependent glucose uptake.
Asunto(s)
Glucosa/metabolismo , Insulina/metabolismo , Ácidos Oléicos/farmacología , Transducción de Señal/efectos de los fármacos , Estearatos/farmacología , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipocitos/ultraestructura , Animales , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Membrana Celular/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Ratones , Ácidos Oléicos/química , Fosforilación/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Estearatos/química , Vesículas Transportadoras/efectos de los fármacosRESUMEN
We report the preparation of multivalent amide-sialoside-decorated human serum albumin (HSA) and bovine serum albumin (BSA) as mimics of natural mucin and bioshields against influenza virus infection. Free sialic acid with an amine on C-2 was covalently attached to the protein scaffolds using di-(N-succinimidyl) adipate. Dynamic light scattering (DLS) showed that the synthetic neomucins were able to act as bioshields and aggregate the influenza virion particles. The dissociation constants (KD) of the interactions between the prepared glycoconjugates and three different viral strains were measured by isothermal titration calorimetry (ITC) indicating the multivalent presentation of sialyl ligands on the HSA and BSA backbones can dramatically enhance the adsorbent capability compared to the corresponding monomeric sialoside. Hemagglutinin inhibition (HAI) and neuraminidase inhibition (NAI) assays showed that the glycoconjugates acted as moderate HA and NA inhibitors, thus impeding viral infection. Moreover, the different binding affinities of the glycoproteins to HA and NA proteins from different influenza viruses demonstrated the importance of HA/NA balance in viral replication and evolution. These findings provide a foundation for the development of antiviral drugs and viral adsorbent materials based on mimicking the structure of mucin.
Asunto(s)
Antivirales/farmacología , Glicerol/farmacología , Gripe Humana/prevención & control , Mucinas/metabolismo , Orthomyxoviridae/efectos de los fármacos , Estearatos/farmacología , Amidas/química , Amidas/farmacología , Animales , Antivirales/química , Bovinos , Combinación de Medicamentos , Glicerol/química , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Humanos , Estructura Molecular , Mucinas/química , Neuraminidasa/antagonistas & inhibidores , Neuraminidasa/metabolismo , Albúmina Sérica Bovina/metabolismo , Albúmina Sérica Humana/metabolismo , Ácidos Siálicos/química , Ácidos Siálicos/farmacología , Estearatos/químicaRESUMEN
Conjugated polymer nanoparticles (CPNs) have emerged as highly photostable probes for optical and photoacoustic imaging. However, the aggregation of conjugated polymer (CP) molecules upon nanoparticle formation is associated with fluorescence quenching, poor yields and mutable particle sizes. This study investigated whether the CP encapsulation within the liquid midchain triglyceride (MCT) core of lipid nanocapsules (LNCs) may achieve reduced packing of CP chains leading to a stable system with enhanced optical features. The red- and near infrared-emitting CPs, CN-PPV and PCPDTBT, showed precipitation and aggregation-induced quenching with concentrations >~25 µg/mL in MCT alone. Despite this, CP encapsulation within LNCs abolished quenching at concentrations up to 1500 µg/mL. PCPDTBT-LNCs exhibited a quantum yield of 2.8% and a higher signal:background ratio in an optical imaging phantom compared to literature reports of PCPDTBT encapsulated in PEG-PLGA nanoparticles. In contrast, PCPDTBT-LNCs had slightly lower photoacoustic amplitudes than reported PEG-PLGA systems. CP-LNCs were also stable in size (32 ± 0.7 nm) and photoluminescence over 21 days at 4 °C, 25 °C and 37 °C. In summary, encapsulation of CP within the liquid core of lipid nanocapsules enhances the optical properties of fluorescent CP.
Asunto(s)
Colorantes Fluorescentes/química , Nanocápsulas/química , Imagen Óptica/métodos , Polietilenglicoles/química , Polímeros/química , Estearatos/química , Triglicéridos/química , Animales , Colorantes Fluorescentes/administración & dosificación , Colorantes Fluorescentes/metabolismo , Humanos , Lípidos , Ratones , Nanocápsulas/administración & dosificación , Imagen Óptica/tendencias , Polietilenglicoles/administración & dosificación , Polietilenglicoles/metabolismo , Polímeros/administración & dosificación , Polímeros/metabolismo , Estearatos/administración & dosificación , Estearatos/metabolismo , Triglicéridos/administración & dosificación , Triglicéridos/metabolismoRESUMEN
Therapeutic advances for osteosarcoma have stagnated over the past several decades, leading to an unmet clinical need for patients. The purpose of this study was to develop a novel therapy for osteosarcoma by reformulating and validating niclosamide, an established anthelminthic agent, as a niclosamide stearate prodrug therapeutic (NSPT). We sought to improve the low and inefficient clinical bioavailability of oral dosing, especially for the relatively hydrophobic classes of anticancer drugs. Nanoparticles were fabricated by rapid solvent shifting and verified using dynamic light scattering and UV-vis spectrophotometry. NSPT efficacy was then studied in vitro for cell viability, cell proliferation, and intracellular signaling by Western blot analysis; ex vivo pulmonary metastatic assay model; and in vivo pharmacokinetic and lung mouse metastatic model of osteosarcoma. NSPT formulation stabilizes niclosamide stearate against hydrolysis and delays enzymolysis; increases circulation in vivo with t 1/2 approximately 5 hours; reduces cell viability and cell proliferation in human and canine osteosarcoma cells in vitro at 0.2-2 µmol/L IC50; inhibits recognized growth pathways and induces apoptosis at 20 µmol/L; eliminates metastatic lesions in the ex vivo lung metastatic model; and when injected intravenously at 50 mg/kg weekly, it prevents metastatic spread in the lungs in a mouse model of osteosarcoma over 30 days. In conclusion, niclosamide was optimized for preclinical drug delivery as a unique prodrug nanoparticle injected intravenously at 50 mg/kg (1.9 mmol/L). This increased bioavailability of niclosamide in the blood stream prevented metastatic disease in the mouse. This chemotherapeutic strategy is now ready for canine trials, and if successful, will be targeted for human trials in patients with osteosarcoma.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias Óseas/tratamiento farmacológico , Niclosamida/farmacología , Osteosarcoma/tratamiento farmacológico , Profármacos/farmacología , Estearatos/farmacología , Animales , Antinematodos/química , Antinematodos/farmacocinética , Antinematodos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacocinética , Apoptosis , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Proliferación Celular , Perros , Evaluación Preclínica de Medicamentos , Reposicionamiento de Medicamentos , Humanos , Ratones , Ratones Endogámicos C57BL , Niclosamida/química , Niclosamida/farmacocinética , Osteosarcoma/metabolismo , Osteosarcoma/patología , Profármacos/química , Profármacos/farmacocinética , Estearatos/química , Estearatos/farmacocinética , Distribución Tisular , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Structuring of vegetable oils has potential application in food, pharmaceutical and cosmetic products. In this study, structuring effects of stearic acid derivatives on sunflower seed oil were systematically investigated by experimental and molecular simulation methods. Stearic acid (SA), 12-hydroxy stearic acid (HSA) and 2-hydroxyethyl stearate (HES) were able to structure sunflower seed oil, among which the structuring ability of HES was reported for the first time. The oleogel formed with HSA exhibited good mechanical properties (such as hardness, fracturability, adhesiveness, chewiness and storage modulus), which coincided with its highest solid fat content and degree of crystallinity. Oleogels containing SA and HES showed similar mechanical properties. Both the molecular dynamics (MD) simulation and independent gradient model (IGM) confirmed that the HSA dimer possessed the strongest interaction during the self-assembly process while the dimers of HES and SA had similar interactions, which could explain their structuring performance.
Asunto(s)
Estearatos/química , Ácidos Esteáricos/química , Aceite de Girasol/química , Almacenamiento de Alimentos , Dureza , Modelos Moleculares , Simulación de Dinámica Molecular , Compuestos Orgánicos/química , TemperaturaRESUMEN
BACKGROUND: This study aimed to reduce the amount of sulfobutylether-ß-cyclodextrin (SBECD) used in the marketed voriconazole injections to meet the clinical needs of patients with moderate-to-severe renal impairment (creatinine clearance rate <50 mL/min). OBJECTIVE: This study found that the surfactant Kolliphor® HS 15 (HS 15) and SBECD had significant synergistic effects on solubilizing voriconazole, and a novel voriconazole complex delivery system (VRC-CD/HS 15) was established. METHODS: The complex system was characterized, and its antifungal activity was studied by dynamic light scattering, dialysis bag method, disk diffusion, and broth microdilution. RESULTS: Compared with the control, its encapsulation efficiency (90.07±0.48%), drug loading (7.37±0.25%) and zeta potential (-4.36±1.37 mV) were increased by 1.54%, 41.19%, and 296.36%, respectively; its average particle size (13.92±0.00 nm) was reduced by 15.69%, so the complex system had better stability. Simultaneously, its drug release behavior was similar to that of the control, and it was a first-order kinetic model. Antifungal studies indicated that the complex system had noticeable antifungal effects. With the increase of drug concentration, the inhibition zone increased. The minimum inhibitory concentrations of the complex system against Cryptococcus neoformans, Aspergillus niger and Candida albicans were 0.0313 µg/mL, 1 µg/mL and 128 µg/mL, respectively. CONCLUSION: It showed a significant inhibitory effect on C. neoformans and had a visible therapeutic effect on Kunming mice infected with C. neoformans. Consequently, VRC-CD/HS 15 had better physicochemical properties and still had an apparent antifungal effect, and was promising as a potential alternative drug for clinical application.
Asunto(s)
Antifúngicos/administración & dosificación , Criptococosis/tratamiento farmacológico , Portadores de Fármacos/administración & dosificación , Polietilenglicoles/administración & dosificación , Estearatos/administración & dosificación , Tensoactivos/administración & dosificación , Voriconazol/administración & dosificación , beta-Ciclodextrinas/administración & dosificación , Animales , Antifúngicos/química , Aspergillus niger/efectos de los fármacos , Aspergillus niger/crecimiento & desarrollo , Candida albicans/efectos de los fármacos , Candida albicans/crecimiento & desarrollo , Cryptococcus neoformans/efectos de los fármacos , Cryptococcus neoformans/crecimiento & desarrollo , Portadores de Fármacos/química , Liberación de Fármacos , Femenino , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Polietilenglicoles/química , Estearatos/química , Tensoactivos/química , Voriconazol/química , beta-Ciclodextrinas/químicaRESUMEN
Banana plants (Musa spp.) are susceptible to infection by many plant-parasitic nematodes, including Meloidogyne incognita. In this study, a mixed fermentation broth of chicken manure (CM) and cassava ethanol wastewater (CEW) was used to inhibit M. incognita by reducing egg hatching and by having a lethal effect on second-stage juvenile nematodes (J2s). It also alleviated nematode damage and promoted banana plant growth. Using gas chromatography-mass spectrometry (GC-MS), we identified methyl palmitate and methyl stearate as bioactive compounds. These bioactive compounds repelled J2s and inhibited egg hatching; reduced root galls, egg masses, and nematodes in soil; and downregulated the essential parasitic nematode genes Mi-flp-18 and 16D10. A Caenorhabditis elegans offspring assay showed that low concentrations of the fermentation broth, methyl palmitate, and methyl stearate were safe for its life cycle. This study explored the effective and environmentally safe strategies for controlling root-knot nematodes.
Asunto(s)
Antinematodos/farmacología , Musa/parasitología , Palmitatos/farmacología , Enfermedades de las Plantas/parasitología , Estearatos/farmacología , Tylenchoidea/efectos de los fármacos , Animales , Antinematodos/química , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/crecimiento & desarrollo , Cromatografía de Gases y Espectrometría de Masas , Palmitatos/química , Raíces de Plantas/parasitología , Estearatos/química , Tylenchoidea/crecimiento & desarrolloRESUMEN
PURPOSE: Development of zeta potential changing SEDDS containing newly synthesized derivative stearic acid phosphotyrosine amide. METHODS: Stearoyl chloride was conjugated with phosphotyrosine, which is substrate for the brush border enzyme intestinal alkaline phosphate. The synthesized derivative was implemented in different SEDDS formulations and the zeta potential changing properties and the concluding mucus diffusion abilities were evaluated. RESULTS: Stearic acid phosphotyrosine amide was successfully synthesized and incorporated into SEDDS. A SEDDS formulation containing the new derivative showed a zeta potential of -14 mV before, and + 2 mV after enzymatic cleavage by intestinal alkaline phosphatase. Experiments on a Caco-2 monolayer demonstrated that the phosphate cannot only be cleaved by isolated enzyme, but also by enzyme, which was expressed by cells. The mucus diffusion abilities of the untreated, negatively charged SEDDS were significantly higher compared to the enzymatically cleaved, positively charged SEDDS. CONCLUSION: The developed stearic acid phosphotyrosine represents a promising excipient for zeta potential changing SEDDS. Graphical Abstract.
Asunto(s)
Amidas/química , Portadores de Fármacos/síntesis química , Fosfotirosina/química , Estearatos/química , Animales , Células CACO-2 , Bovinos , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Emulsionantes/química , Emulsiones , Excipientes/química , Humanos , Mucosa Intestinal/metabolismo , Propiedades de SuperficieRESUMEN
Human diseases like viral organisms for example, hepatitis, HIV and etc., attack the health and caused large mortality in populations by many years. So finding novel delivery vehicles based antiviral drugs employing nano-materials is of high universal interest. In current approach a very biocompatible biodegradable nano-biopolymer anionic linear globular dendrimer second generation G2 was elaborately conjugated to a well-known anti-HIV drug Azidovudine and thereafter was characterized by different analytical techniques like AFM, Zeta sizer, 1HNMR, FTIR and LC-Mass spectroscopy. Then, Anionic Linear Globular DendrimerG2-Zidovudine Nano-Conjugate was assessed on human normal cells (toxicity assay by XTT test) and also HIV cell model and the results showed that Anionic Linear Globular DendrimerG2-Zidovudine Nano-Conjugate Significantly Decreased Retroviral Activity without any human cell toxicity respectively. Based on current experimental data such nano-compositions is proposed for further in vivo anti-HIV assays as well.
Asunto(s)
Antirretrovirales/administración & dosificación , Supervivencia Celular/efectos de los fármacos , Dendrímeros/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Nanoconjugados/administración & dosificación , Zidovudina/administración & dosificación , Aniones , Antirretrovirales/química , Supervivencia Celular/fisiología , Dendrímeros/química , Relación Dosis-Respuesta a Droga , Células HEK293 , VIH-1/efectos de los fármacos , VIH-1/fisiología , Humanos , Nanoconjugados/química , Polietilenglicoles/administración & dosificación , Polietilenglicoles/química , Estearatos/administración & dosificación , Estearatos/química , Zidovudina/químicaRESUMEN
Fatty acid esters of 3-monochloropropane 1,2-diol (3-MCPD esters) are processing-induced food toxicants, with the kidney as their major target organ. For the first time, this study treated Sprague Dawley (SD) rats with 3-MCPD 1-monooleate at 10 and 100 mg/kg BW/day and 1-monostearate at 15 and 150 mg/kg BW/day for 90 days and examined for their potential semi-long-term nephrotoxicity and the associated molecular mechanisms. No bodyweight difference was observed between groups during the study. Both 3-MCPD 1-monooleate and 1-monostearate resulted in a dose-dependent increase of serum urea creatinine, uric acid and urea nitrogen levels, and histological renal impairment. The proteomic analysis of the kidney samples showed that the 3-MCPD esters deregulated proteins involved in the pathways for ion transportation, apoptosis, the metabolism of xenobiotics, and enzymes related to endogenous biological metabolisms of carbohydrates, amino acids, nitrogen, lipids, fatty acids, and the tricarboxylic acid (TCA) cycle, providing partial explanation for the nephrotoxicity of 3-MCPD esters.
Asunto(s)
Enfermedades Renales/metabolismo , Riñón/efectos de los fármacos , Estearatos/toxicidad , alfa-Clorhidrina/toxicidad , Animales , Creatinina/orina , Ésteres/metabolismo , Ésteres/toxicidad , Humanos , Riñón/metabolismo , Enfermedades Renales/etiología , Enfermedades Renales/genética , Enfermedades Renales/orina , Masculino , Proteómica , Ratas , Ratas Sprague-Dawley , Estearatos/química , Estearatos/metabolismo , Ácido Úrico/orina , alfa-Clorhidrina/metabolismoRESUMEN
Biomimetic design has been extensively investigated. The only FDA-approved biomimetic albumin-bound paclitaxel may not be beneficial to some treated patients due to rapid dissociation upon intravenous infusion and no substantial improvement in the drug's pharmacokinetics or biodistribution. Herein, we developed an alternative and injectable preformed albumin-bound anticancer drug delivery. We combined HSA, Kolliphor HS 15 (HS15), and pirarubicin (THP) via purely physical forces in a thin-film hydration method to obtain an albumin-bound complex of HSA-THP. The lack of any chemical reactions preserves HSA bioactivity, in contrast to the destroyed secondary structure within AN-THP (albumin nanoparticle of THP) for the harsh manipulation during preparation. In vitro, HSA-THP showed a significantly higher cellular uptake efficiency than THP, and the complex was more cytotoxic. In vivo, HSA-THP showed longer half-life than THP. It also exhibited greater tumor accumulation and tumor penetration via gp60- and SPARC-mediated biomimetic transport than THP and AN-THP. As a result, HSA-THP showed strong antitumor and antimetastasis efficacy, with relatively little toxicity. These results suggest the clinical potential of biomimetic tumor-targeted drug delivery.
Asunto(s)
Albúminas/química , Antineoplásicos/administración & dosificación , Doxorrubicina/análogos & derivados , Sistemas de Liberación de Medicamentos/métodos , Neoplasias/tratamiento farmacológico , Polietilenglicoles/química , Estearatos/química , Animales , Antineoplásicos/química , Línea Celular Tumoral , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/instrumentación , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Metástasis de la Neoplasia/prevención & control , Neoplasias/patología , Ratas , Ratas Sprague-DawleyRESUMEN
Aim: We aimed to construct human serum albumin-Kolliphor® HS 15 nanoparticles (HSA-HS15 NPs) to overcome the limitations in targeted therapy for rheumatoid arthritis (RA) and enhance the safety of drug-loaded HSA NPs. Methodology: Celastrol (CLT)-loaded HSA-HS15 NPs were prepared and the properties were adequately investigated; the treatment effect were evaluated in RA rats; in vitro and in vivo studies were performed to explain the mechanism. Results: CLT-HSA-HS15 NPs had remarkable treatment ability and enhanced safety in the treatment of RA compared with free CLT and CLT-HSA NPs. Conclusion: HSA-HS15 NPs could be a safe and efficient therapeutic strategy for the treatment of RA, because of the inflammatory targeting ability of albumin, the added HS15 and ELVIS effect (extravasation through leaky vasculature followed by inflammatory cell-mediated sequestration) of nanoparticles.
Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Portadores de Fármacos/química , Nanopartículas/química , Polietilenglicoles/química , Albúmina Sérica Humana/uso terapéutico , Estearatos/química , Animales , Sistemas de Liberación de Medicamentos/métodos , Humanos , Masculino , Ratones , Triterpenos Pentacíclicos , Células RAW 264.7 , Ratas , Ratas Sprague-Dawley , Albúmina Sérica Humana/química , Triterpenos/químicaRESUMEN
Sodium stearoyl lactylate (SSL) was used as a gelling agent to structure oleogels at concentrations of 7%, 9%, 11%, and 13% (w/w) with sunflower oils in this study, respectively. The physical characteristics of oleogels, such as solid fat content (SFC), oil bonding capability (OBC) and firmness, were influenced by SSL crystals. Therefore, the microstructure and interaction of oleogels was further investigated by polarizing light microscopy (PLM), X-ray diffraction (XRD), rheology, differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). It was found that the higher concentration of oleogelator resulted in a denser crystalline network, which provided stronger mechanical strength and enhanced the ability to retain the oil phase. Space-spanning networks were attributed to surface interactions among crystals of SSL, such as van der Waals interactions and electrostatic repulsion. Crystal network in the SSL oleogels imitated the typical functionality of crystalline network structures formed by triacylglycerol.