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1.
J Oleo Sci ; 70(8): 1059-1068, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34248093

RESUMO

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".


Assuntos
Ácido Ascórbico/química , Óleo de Milho/química , Ácidos Graxos Insaturados/química , Margarina , Monoglicerídeos/química , Estearatos/química , Manteiga , Comportamento do Consumidor , Ácidos Graxos Insaturados/análise , Humanos , Compostos Orgânicos/química , Oxirredução , Paladar , Triglicerídeos/análise , Triglicerídeos/química
2.
Food Chem ; 356: 129667, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33831829

RESUMO

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.


Assuntos
Doces/análise , Varredura Diferencial de Calorimetria , Culinária/métodos , Dureza , Derivados da Hipromelose/química , Monoglicerídeos/química , Compostos Orgânicos/química , Reologia , Estearatos/química , Ceras/química
3.
Drug Deliv ; 28(1): 487-498, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33657948

RESUMO

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.


Assuntos
Excipientes/química , Mucosa Nasal/metabolismo , Hormônio Paratireóideo/administração & dosagem , Administração Intranasal , Animais , Anuros , Disponibilidade Biológica , Cromatografia Líquida , Ácido Cítrico/química , Ácido Cítrico/toxicidade , Excipientes/toxicidade , Feminino , Masculino , Hormônio Paratireóideo/farmacocinética , Hormônio Paratireóideo/toxicidade , Permeabilidade , Polietilenoglicóis/química , Polietilenoglicóis/toxicidade , Ratos , Ratos Sprague-Dawley , Estearatos/química , Estearatos/toxicidade , Espectrometria de Massas em Tandem
4.
Inflammopharmacology ; 29(1): 107-121, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33179175

RESUMO

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.


Assuntos
Artrite Experimental/tratamento farmacológico , Dextranos/química , Sistemas de Liberação de Medicamentos , Indometacina/farmacologia , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Artrite Experimental/fisiopatologia , Liberação Controlada de Fármacos , Edema/tratamento farmacológico , Edema/patologia , Adjuvante de Freund , Indometacina/administração & dosagem , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Micelas , Polímeros/química , Ratos , Ratos Wistar , Estearatos/química
5.
Molecules ; 25(23)2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33297487

RESUMO

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.


Assuntos
Alcenos/química , Alumínio/química , Biodegradação Ambiental , Hidróxidos/química , Magnésio/química , Nanocompostos/química , Estearatos/química , Succinatos/química , Fenômenos Químicos , Fenômenos Mecânicos , Oceanos e Mares , Polímeros , Análise Espectral
6.
Biochimie ; 177: 98-107, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32822725

RESUMO

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.


Assuntos
Glucose/metabolismo , Insulina/metabolismo , Ácidos Oleicos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Estearatos/farmacologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/ultraestrutura , Animais , Metabolismo dos Carboidratos/efeitos dos fármacos , Membrana Celular/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Camundongos , Ácidos Oleicos/química , Fosforilação/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estearatos/química , Vesículas Transportadoras/efeitos dos fármacos
7.
J Oleo Sci ; 69(9): 1043-1049, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32788510

RESUMO

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.


Assuntos
Hexanóis/química , Estearatos/síntese química , Ondas Ultrassônicas , Biocatálise , Fenômenos Químicos , Enzimas Imobilizadas/química , Esterificação , Estearatos/química , Ácidos Esteáricos/química , Temperatura , Fatores de Tempo
8.
Carbohydr Res ; 495: 108088, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807356

RESUMO

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.


Assuntos
Antivirais/farmacologia , Glicerol/farmacologia , Influenza Humana/prevenção & controle , Mucinas/metabolismo , Orthomyxoviridae/efeitos dos fármacos , Estearatos/farmacologia , Amidas/química , Amidas/farmacologia , Animais , Antivirais/química , Bovinos , Combinação de Medicamentos , Glicerol/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Humanos , Estrutura Molecular , Mucinas/química , Neuraminidase/antagonistas & inibidores , Neuraminidase/metabolismo , Soroalbumina Bovina/metabolismo , Albumina Sérica Humana/metabolismo , Ácidos Siálicos/química , Ácidos Siálicos/farmacologia , Estearatos/química
9.
Pharm Nanotechnol ; 8(5): 391-398, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32787769

RESUMO

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.


Assuntos
Antibióticos Antineoplásicos/farmacocinética , Doxorrubicina/análogos & derivados , Lecitinas/química , Polietilenoglicóis/química , Estearatos/química , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/sangue , Antibióticos Antineoplásicos/química , Preparações de Ação Retardada , Doxorrubicina/administração & dosagem , Doxorrubicina/sangue , Doxorrubicina/química , Doxorrubicina/farmacocinética , Composição de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Injeções Intravenosas , Lipossomos , Masculino , Tamanho da Partícula , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/farmacocinética , Ratos Sprague-Dawley , Tecnologia Farmacêutica
10.
Eur J Pharm Biopharm ; 154: 297-308, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32707286

RESUMO

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.


Assuntos
Corantes Fluorescentes/química , Nanocápsulas/química , Imagem Óptica/métodos , Polietilenoglicóis/química , Polímeros/química , Estearatos/química , Triglicerídeos/química , Animais , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/metabolismo , Humanos , Lipídeos , Camundongos , Nanocápsulas/administração & dosagem , Imagem Óptica/tendências , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/metabolismo , Polímeros/administração & dosagem , Polímeros/metabolismo , Estearatos/administração & dosagem , Estearatos/metabolismo , Triglicerídeos/administração & dosagem , Triglicerídeos/metabolismo
11.
Mol Cancer Ther ; 19(7): 1448-1461, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32371588

RESUMO

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.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Niclosamida/farmacologia , Osteossarcoma/tratamento farmacológico , Pró-Fármacos/farmacologia , Estearatos/farmacologia , Animais , Antinematódeos/química , Antinematódeos/farmacocinética , Antinematódeos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacocinética , Apoptose , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Proliferação de Células , Cães , Avaliação Pré-Clínica de Medicamentos , Reposicionamento de Medicamentos , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Niclosamida/química , Niclosamida/farmacocinética , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Estearatos/química , Estearatos/farmacocinética , Distribuição Tecidual , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Food Chem ; 324: 126801, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32353654

RESUMO

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.


Assuntos
Estearatos/química , Ácidos Esteáricos/química , Óleo de Girassol/química , Armazenamento de Alimentos , Dureza , Modelos Moleculares , Simulação de Dinâmica Molecular , Compostos Orgânicos/química , Temperatura
13.
J Agric Food Chem ; 68(24): 6502-6510, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32463695

RESUMO

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.


Assuntos
Antinematódeos/farmacologia , Musa/parasitologia , Palmitatos/farmacologia , Doenças das Plantas/parasitologia , Estearatos/farmacologia , Tylenchoidea/efeitos dos fármacos , Animais , Antinematódeos/química , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/crescimento & desenvolvimento , Cromatografia Gasosa-Espectrometria de Massas , Palmitatos/química , Raízes de Plantas/parasitologia , Estearatos/química , Tylenchoidea/crescimento & desenvolvimento
14.
Curr Drug Metab ; 21(5): 379-389, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32432999

RESUMO

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.


Assuntos
Antifúngicos/administração & dosagem , Criptococose/tratamento farmacológico , Portadores de Fármacos/administração & dosagem , Polietilenoglicóis/administração & dosagem , Estearatos/administração & dosagem , Tensoativos/administração & dosagem , Voriconazol/administração & dosagem , beta-Ciclodextrinas/administração & dosagem , Animais , Antifúngicos/química , Aspergillus niger/efeitos dos fármacos , Aspergillus niger/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/crescimento & desenvolvimento , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Feminino , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Polietilenoglicóis/química , Estearatos/química , Tensoativos/química , Voriconazol/química , beta-Ciclodextrinas/química
15.
Pharm Res ; 37(4): 79, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32253523

RESUMO

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.


Assuntos
Amidas/química , Portadores de Fármacos/síntese química , Fosfotirosina/química , Estearatos/química , Animais , Células CACO-2 , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Emulsificantes/química , Emulsões , Excipientes/química , Humanos , Mucosa Intestinal/metabolismo , Propriedades de Superfície
16.
Pak J Pharm Sci ; 33(2): 705-714, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32276917

RESUMO

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.


Assuntos
Antirretrovirais/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Dendrímeros/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Nanoconjugados/administração & dosagem , Zidovudina/administração & dosagem , Ânions , Antirretrovirais/química , Sobrevivência Celular/fisiologia , Dendrímeros/química , Relação Dose-Resposta a Droga , Células HEK293 , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Nanoconjugados/química , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Estearatos/administração & dosagem , Estearatos/química , Zidovudina/química
17.
J Agric Food Chem ; 68(9): 2765-2772, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32045244

RESUMO

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.


Assuntos
Nefropatias/metabolismo , Rim/efeitos dos fármacos , Estearatos/toxicidade , alfa-Cloridrina/toxicidade , Animais , Creatinina/urina , Ésteres/metabolismo , Ésteres/toxicidade , Humanos , Rim/metabolismo , Nefropatias/etiologia , Nefropatias/genética , Nefropatias/urina , Masculino , Proteômica , Ratos , Ratos Sprague-Dawley , Estearatos/química , Estearatos/metabolismo , Ácido Úrico/urina , alfa-Cloridrina/metabolismo
18.
ACS Appl Mater Interfaces ; 11(45): 42534-42548, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31479235

RESUMO

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.


Assuntos
Albuminas/química , Antineoplásicos/administração & dosagem , Doxorrubicina/análogos & derivados , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Polietilenoglicóis/química , Estearatos/química , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/instrumentação , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Metástase Neoplásica/prevenção & controle , Neoplasias/patologia , Ratos , Ratos Sprague-Dawley
19.
Nanomedicine (Lond) ; 14(16): 2169-2187, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31397202

RESUMO

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.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Portadores de Fármacos/química , Nanopartículas/química , Polietilenoglicóis/química , Albumina Sérica Humana/uso terapêutico , Estearatos/química , Animais , Sistemas de Liberação de Medicamentos/métodos , Humanos , Masculino , Camundongos , Triterpenos Pentacíclicos , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Albumina Sérica Humana/química , Triterpenos/química
20.
Food Chem ; 292: 134-142, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31054657

RESUMO

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.


Assuntos
Pão/análise , Estearatos/química , Varredura Diferencial de Calorimetria , Cristalização , Compostos Orgânicos/análise , Compostos Orgânicos/química , Reologia , Espectroscopia de Infravermelho com Transformada de Fourier , Óleo de Girassol/química , Difração de Raios X
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