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1.
Chem Pharm Bull (Tokyo) ; 68(1): 77-90, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31902903

RESUMO

Novel 3,5-dimethylpyridin-4(1H)-one scaffold compounds were synthesized and evaluated as AMP-activated protein kinase (AMPK) activators. Unlike direct AMPK activators, this series of compounds showed selective cell growth inhibitory activity against human breast cancer cell lines. By optimizing the lead compound (4a) from our library, 2-[({1'-[(4-fluorophenyl)methyl]-2-methyl-1',2',3',6'-tetrahydro[3,4'-bipyridin]-6-yl}oxy)methyl]-3,5-dimethylpyridin-4(1H)-one (25) was found to have potent AMPK activating activity. Compound 25 also showed good aqueous solubility while maintaining the unique selectivity in cell growth inhibitory activity.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Piridonas/química , Proteínas Quinases Ativadas por AMP/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Piridonas/síntese química , Piridonas/farmacologia , Solubilidade , Relação Estrutura-Atividade
2.
Food Chem ; 305: 125435, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31494497

RESUMO

Soluble dietary fibre (SDF) of micronized and non-micronized powders of lotus root nodes were investigated based on its adsorption and activity inhibition of pancreatic lipase (PL) by using circular dichroism, fluorescence spectroscopy and modification. Results showed that SDF2 (SDF from micronized powders of lotus root nodes) had stronger PL adsorption and enzyme activity inhibition than SDF1 (SDF from non-micronized powders of lotus root nodes). Specifically, SDF2 showed more binding sites than SDF1 in PL. There were hydrogen bonds and van der Waals interactions between SDF and PL, with Trp on PL probably serving as the main binding site. Carboxyl groups exhibited a stronger inhibition on PL by carboxymethyl and hydroxypropyl modification. The common mechanisms between SDF1 and SDF2 can be attributed to the combination between Trp and carboxyl groups, while the differences may be generated by the variations in structures or chemical groups induced by micronization.


Assuntos
Fibras na Dieta , Lipase/metabolismo , Metabolismo dos Lipídeos , Lotus/química , Adsorção , Hidrólise , Preparações de Plantas/química , Raízes de Plantas/química , Pós/química , Solubilidade
3.
Food Chem ; 305: 125433, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31499293

RESUMO

Native high methoxy citrus pectin (NP) was de-esterified by pectin methyl esterase to produce modified pectins [MP (42, 37, and 33)] having different degrees of esterification. Complex coacervation between a pea protein isolate (PPI) and each pectin was investigated as a function of pH (8.0-1.5) and mixing ratio (1:1-30:1, PPI-pectin). Complex formation was found to be optimal for biopolymer-mixing ratios of 8:1, 8:1, 25:1 and 25:1 for PPI complexed with NP, MP42, MP37 and MP33, respectively, at pHs 3.6, 3.5, 3.9 and 3.9. And, the critical pHs associated with complex formation (accessed by turbidity) was found to shift significantly to higher pHs as the degree of esterification of the pectin decreased, whereas the shift in the pH corresponding to their initial interactions was minimal with degree of esterification. Complexation of PPI with NP and MP42 greatly improved the protein solubility.


Assuntos
Proteínas de Ervilha/química , Pectinas/química , Hidrolases de Éster Carboxílico/metabolismo , Citrus/enzimologia , Concentração de Íons de Hidrogênio , Pectinas/metabolismo , Solubilidade
4.
Food Chem ; 306: 125610, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31586816

RESUMO

The industrial implementation of new eco-friendly solvents has highlighted the need to analyse both the structures and thermophysical properties of these solvents. Here, two deep eutectic solvents (DESs) used in the agro-food field were studied: xylitol:choline chloride:water (1:2:3 M ratio), XoCH, and citric acid:choline chloride:water (1:1:6 M ratio), CiCH. The H-bond network between the components of each DES was evaluated and the diffusion coefficients at 298.15 K were calculated using NMR spectroscopy. In addition, seven thermophysical properties were determined from 278.15 to 338.15 K. Also, the solubility of quercetin in water and in the two eutectic mixtures was measured and the interactions between components were studied. NMR experiments revealed the presence of water within the supramolecular structure of XoCH, but CiCH is a "DES-in-water" solution. Based on the results, XoCH is the most compact mixture. Finally, quercetin was remarkably more soluble in the studied DESs than in pure water.


Assuntos
Ácido Cítrico/química , Quercetina/química , Xilitol/química , Colina/química , Solubilidade , Solventes/química , Água/química
5.
Food Chem ; 306: 125589, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31606629

RESUMO

The combined effects of plasma-activated water (PAW) and heat-moisture treatments (HMT) on the structure, physicochemical properties and in vitro digestibility of waxy (WMS) and normal maize starches (NMS) were investigated. X-ray diffraction results revealed that the relative crystallinity of starches treated with PAW-HMT increased without crystalline type transition compared to DW-HMT. Through the Fourier transform infrared spectroscopy and Raman spectroscopy, the short-range order of starches treated with PAW-HMT was improved. Differential scanning calorimetry analysis shown that PAW-HMT increased gelatinization temperatures for NMS while decreasing gelatinization temperatures for WMS. The solubility of starches treated with PAW-HMT was higher than that of DW-HMT while the swelling power decreased. Importantly, the resistant starch (RS) content of starches treated by PAW-HMT increased compared to the starches treated by DW-HMT or native starch. This study provides a novel green method to modify the structure, lower starch digestibility and improve the RS content of starch.


Assuntos
Amido/química , Ceras/química , Zea mays/química , Varredura Diferencial de Calorimetria , Temperatura Alta , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Água/química , Difração de Raios X
6.
Food Chem ; 306: 125615, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31622833

RESUMO

Phycocyanin (PC), a plant-based protein with interesting biological activity, is rarely directly applied in the food industry because it has structural and functional limitations. This study combined ultra-high-pressure (UHP) treatment with glycation to improve PC functionality and explored resulting structural changes using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, scanning electron microscopy, Fourier-transform infrared spectroscopy, circular dichroism, and UV-visible spectroscopy. The UHP treatment obviously improved the speed and degree of glycation and the composite-modified PC (CM-PC) showed high solubility and good emulsifying and foaming performance. Scanning electron microscopy images showed the CM-PC surface was loose and fluffy. Gel electrophoresis, Fourier-transform infrared spectroscopy, and circular dichroism results demonstrated that the content of α-helix decreased from 78.1% in PC to 26.6% in CM-PC, and hydroxyl groups were introduced. UV-visible spectroscopy showed that the mechanism of composite modification involved stretching of the PC and promotion of binding with sugars.


Assuntos
Ficocianina/química , Spirulina/química , Dicroísmo Circular , Eletroforese em Gel de Poliacrilamida , Emulsões/metabolismo , Glicosilação , Pressão , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier
7.
Food Chem ; 307: 125543, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31634760

RESUMO

Phosphate fertilisation affects the growth, development and quality of Tartary buckwheat. In this study, the effect of different phosphorus levels, including 0, 15, 75, and 135 kg/ha (non-, low-, medium-, and high-phosphorus levels, respectively), on the characteristics of starch from Tartary buckwheat were investigated in 2015 and 2017. With increased phosphorus level, the median diameter of starch granules and the apparent amylose content initially decreased and then increased. All starch samples showed the features of A-type X-ray diffraction patterns. Starches under medium-phosphorus treatment showed higher relative crystallinity than those under non-phosphorus treatment, as well as the highest solubility, gelatinisation enthalpy and transmittance among all starches. Starches under low-phosphorus treatment exhibited higher pasting properties than those under non-phosphorus treatment. This research revealed that phosphorus treatments and year significantly affected the physicochemical properties of Tartary buckwheat starch, and can provide information for the applications of starch in the food and non-food industries.


Assuntos
Fagopyrum/química , Fertilizantes , Fosfatos/farmacologia , Amido/química , Amilose/química , Fenômenos Químicos , Fagopyrum/efeitos dos fármacos , Solubilidade
8.
Food Chem ; 308: 125569, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31644967

RESUMO

In this study, the solubility of phloretin (PT) was enhanced via steviol glycoside (STE)-based micelle (MC) and solid dispersion (SD). Computer simulation, characterization, interaction with serum albumin (SA) and in vitro release were carried out to investigate the solubilization mechanisms and the difference in their solubilization capacities. For PT-loaded MC (STE-PT MC), PT was encapsulated into the hydrophobic core of a spherical micelle with a droplet diameter of 5 nm. For PT-loaded SD (STE-PT SD), PT was completely dispersed with the amorphous state in STE. Most of those PTs were directly dissolved in water, and few were encapsulated by STE micelles. The amorphous state combined with relatively large micelles contributed to the high solubilization capacity of STE-PT SD. In addition, PT of STE-PT SD exhibited a higher dissolution rate and more effective interaction with SA than that of STE-PT MC. No undesirable chemical interaction between PT and STE occurred.


Assuntos
Diterpenos de Caurano/química , Glucosídeos/química , Floretina/química , Interações Hidrofóbicas e Hidrofílicas , Micelas , Floretina/análise , Solubilidade , Água/química
9.
Food Chem ; 308: 125600, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31648091

RESUMO

A novel blue pigment was first isolated from Streptomyces sp. A1013Y. The purified component was identified as 4,8,13-trihydroxy-6,11-dione-trihydrogranaticins A (TDTA). Its physical properties were found to be: Molecular weight 462 Da; Color value, E0.1%1cm580 nm = 80; Solubility, it dissolved in organic solvents. In addition, the color of TDTA changed with pH but was found to be relatively stable between 20 and 100 °C, from pH 3 to pH 11, and under UV-light or darkness. TDTA's functional properties was as follows: TDTA showed excellent free radical scavenging properties, IC50 41.04 µg/mL and 13.75 µg/mL using 2, 20-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-n-(3, 2-ethyl-benzothiazole-6-sulfonic acid) ammonium salt (ABTS) respectively. TDTA might be a promising source of natural pigment and bioactive compound used as additive in food industry.


Assuntos
Streptomyces/química , Benzotiazóis/química , Compostos de Bifenilo/química , Cor , Picratos/química , Pigmentação , Solubilidade , Solventes
10.
J Colloid Interface Sci ; 558: 137-144, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31586733

RESUMO

Platinum oxide (PtOx) nanoparticles (NPs) have been shown to possess anticancer activity by releasing ionic Pt species under biological conditions. However, the dissolution kinetics and the changes in the chemical state of Pt during PtOx dissolution have not yet been studied. To fill this gap, we prepared a composite (designated as PtOx@MMT-2) containing PtOx NPs on hollow mesoporous silica nanospheres and studied the dissolution of the material in different biorelevant media. We found that the release of Pt was retarded due to the adsorption of biomolecules on PtOx NPs during the degradation of host silica. The biomolecules adsorption also lowered the accessibility of PtOx NPs, resulting in the reduced catalase-like activity of the NPs. In line with the results, the cytotoxicity of PtOx@MMT-2, which was positively correlated to the amount of Pt uptake, was reduced by biomolecules adsorption. Our findings should be applicable to other metal (oxide) NPs under biological conditions and may provide implications for the design of nanomaterials for practical therapeutic applications.


Assuntos
Materiais Biocompatíveis/química , Nanopartículas/química , Óxidos/química , Platina/química , Dióxido de Silício/química , Adsorção , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células HeLa , Humanos , Nanopartículas/uso terapêutico , Solubilidade
11.
J Sci Food Agric ; 100(1): 50-58, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31435937

RESUMO

BACKGROUND: Protein hydrolysate powder was prepared from non-penaeid shrimp (Acetes indicus) by enzymatic hydrolysis using Alcalase enzyme. Extraction conditions such as pH (6.5, 7.5 and 8.5), enzyme to substrate ratio (1.0, 1.5 and 2.0) and temperature (40, 50 and 60 °C) were optimized against the degree of hydrolysis using response surface methodology. RESULTS: Protein hydrolysate comprised of 740 g kg-1 protein, 150 g kg-1 ash and 90 g kg-1 fat contents. The amino acid score showed superior attributes with 56% essential amino acids. Furthermore, the functional properties of spray-dried protein hydrolysates were evaluated. Protein solubility was found to be the 90.20% at pH 2 and 96.92% at pH 12. Emulsifying properties were found to vary with the concentration of protein hydrolysates and the highest emulsifying capacity (26.67%) and emulsion stability (23.33%) were found at a concentration of 20 mg mL-1 . The highest and the lowest foaming capacity were observed at pH 6 and pH 10 with a concentration of 20 mg mL-1 . The water holding capacity of protein hydrolysate was found to increase with concentration, with a value of 5.4 mL g-1 at a concentration of 20 mg mL-1 . CONCLUSION: The results of the present study indicate that the use of A. indicus for the production of protein hydrolysate has good functional properties and nutritional value, rendering it suitable for broad industrial food applications. © 2019 Society of Chemical Industry.


Assuntos
Crustáceos/química , Proteínas de Frutos do Mar/química , Aminoácidos/análise , Animais , Biocatálise , Emulsões/química , Manipulação de Alimentos , Hidrólise , Valor Nutritivo , Hidrolisados de Proteína/química , Solubilidade , Subtilisinas/química
12.
Food Chem ; 305: 125479, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31505418

RESUMO

1-o-Galloylglycerol (GG) was synthesized by the enzymatic glycerolysis of propyl gallate (PG) using a food-grade lipase (Lipozyme® 435). The reaction conditions affecting the yield of GG were optimized and a yield of 76.9% ±â€¯1.2% was obtained. GG was characterized by various techniques after being separated from the reaction mixture using liquid-liquid extraction. The water solubility and hydrophilicity of GG were significantly higher than those of gallic acid (GA) and PG. The antioxidant properties, measured by the ferric reducing antioxidant power (FRAP) and hydrogen peroxide (H2O2) scavenging assays, showed that GG exhibited the highest scavenging capacity (GG > GA > PG). From the results of the 1,1-diphenyl-2-picrylhydrazyl (DPPH•) and 2,2'-azinobis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS•+) assays, GG and GA exhibited greater scavenging capacity than PG (GG = GA > PG). These results suggest that GG may be used as a water-soluble antioxidant alternative to GA for food and cosmetic applications.


Assuntos
Antioxidantes/química , Glicerol/química , Ácido Gálico/química , Glicerol/isolamento & purificação , Glicerol/metabolismo , Peróxido de Hidrogênio/química , Lipase/metabolismo , Extração Líquido-Líquido , Espectroscopia de Ressonância Magnética , Galato de Propila/química , Solubilidade , Temperatura Ambiente
13.
Pharm Res ; 36(12): 174, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31667638

RESUMO

PURPOSE: The overall goal of this study was to investigate the dissolution performance and crystallization kinetics of amorphous solid dispersions (ASDs) of a weakly basic compound, posaconazole, dispersed in a pH-sensitive polymeric matrix consisting of hydroxypropyl methylcellulose acetate succinate (HPMC-AS), using fasted-state simulated media. METHODS: ASDs with three different drug loadings, 10, 25 and 50 wt.%, and the commercially available tablets were exposed to acidic media (pH 1.6), followed by transfer to, and dissolution in, intestinal media (pH 6.5). Parallel single stage dissolution experiments in only simulated intestinal media were also performed to better understand the impact of the gastric stage. Different analytical methods, including nanoparticle tracking analysis, powder x-ray diffraction, second harmonic generation and two-photon excitation ultraviolet fluorescence microscopy, were used to characterize the phase behavior of these systems at different stages of dissolution. RESULTS: Results revealed that all ASDs exhibited some degree of drug release upon suspension in acidic media, and were also vulnerable to matrix crystallization. Upon transfer to intestinal media conditions, supersaturation was observed. This was short-lived for some dispersions due to the release of the crystals formed in the acid immersion stage which acted as seeds for crystal growth. Lower drug loading ASDs also exhibited transient formation of amorphous nanodroplets prior to crystallization. CONCLUSIONS: This work emphasizes the significance of assessing the impact of pH change on dissolution and provides a fundamental basis of understanding the phase behavior kinetics of ASDs of weakly basic drugs when formulated with pH sensitive polymers.


Assuntos
Portadores de Fármacos/química , Metilcelulose/análogos & derivados , Triazóis/química , Cristalização , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Cinética , Metilcelulose/química , Nanopartículas/química , Tamanho da Partícula , Transição de Fase , Solubilidade , Temperatura Ambiente
14.
Chem Commun (Camb) ; 55(92): 13880-13883, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31675031

RESUMO

Based on the unique property of preferential sequestration of guest molecules, coacervate microdroplets are proposed as enzyme active membrane-free protocells, in which uricase is loaded for efficient detoxification of uric acid in serum.


Assuntos
Urato Oxidase/metabolismo , Ácido Úrico/metabolismo , Células Artificiais/química , Dextranos/química , Corantes Fluorescentes/química , Humanos , Polietilenos/química , Estabilidade Proteica , Compostos de Amônio Quaternário/química , Solubilidade , Ácido Úrico/sangue
15.
Am J Dent ; 32(5): 229-234, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31675190

RESUMO

PURPOSE: To evaluate the influence of ceramic laminate on color stability, surface microhardness, water sorption, and solubility of resin luting agents. METHODS: Disk-shaped specimens (10 × 2 mm) of dual-cured resin cements (RelyX ARC or RelyX Ultimate) were obtained, and a light-cured luting agent (RelyX Veneer) was used. In Experiment 1, disk-shaped resin cements (n = 10) were submitted to: I) polymerization with or without ceramic laminate (0.7 mm), and II) immersion in distilled water or coffee, 3 hours daily for 20 days. The surface microhardness loss (%SML) was determined, and the color variables were assessed by the CIE L*a*b* system (ΔE, ΔL*) and the shade guide units (ΔSGU). In Experiment 2, other disk-shaped specimens (n = 5) were submitted to polymerization with or without ceramic laminate to assess their water sorption (WS) and solubility (S). Statistical analysis was performed using 3-way ANOVA and Tukey's test for ΔE, ΔL* and %SML; Mann-Whitney, Kruskal-Wallis, and Dunn's tests for ΔSGU; and 2-way ANOVA and Tukey's test for WS and S. The significance level was set at 5%. RESULTS: No statistically significant differences among the resin cements was observed for %SML, WS, or S, regardless of stain exposure or presence of ceramic laminate during light activation. Coffee caused a significant decrease in ΔL* values. All the resin cements presented visually detectable color alteration for ΔE; however, RelyX Ultimate showed less color change after coffee exposure. RelyX ARC showed the greatest color change in water. RelyX Veneer presented the highest values of ΔSGU, compared with the other resin cements. The WS, S, and %SML of resin cements were not influenced by the staining solution or the presence of ceramic laminate during light activation; however, RelyX Ultimate resin cement presented the best color stability. CLINICAL SIGNIFICANCE: Resin cements can present color changes over time, affecting the long-term esthetic success of laminate ceramic restorations. RelyX Ultimate resin cement presented the best color stability, thus making it a suitable indication for cementing ceramic laminates.


Assuntos
Porcelana Dentária , Cimentos de Resina , Cerâmica , Cor , Teste de Materiais , Solubilidade , Água
16.
Am J Dent ; 32(5): 235-239, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31675191

RESUMO

PURPOSE: To evaluate the effect of whitening mouthrinses on sorption (SP) and solubility (SL), percentage of microhardness change (%M), loss of surface (LS), and color change (ΔE) in bulk-fill composites when compared with conventional composites. METHODS: Three bulk-fill composites, Surefil SDR (SF), Filtek Bulk-Fill (BF), and Filtek Bulk-Fill Flow (BFF), and one conventional resin, Filtek Z350 (FZ), were selected. Eighteen samples of each composite were subdivided into three groups based on the type of treatment: Listerine Whitening mouthrinse (LW), Colgate Plax Whitening mouthrinse (CP), and distilled water (DW; control). The samples were prepared according to ISO 4049:2009. Color, roughness, and microhardness were evaluated before and after treatment, while SP and SL values were measured after treatment. The surface morphology of the specimen was examined using scanning electron microscopy. Data were analyzed using two-way ANOVA and Tukey's test. RESULTS: FZ presented significantly lower ΔE when immersed in DW. Additionally, LS was lowest in FZ when compared with the other resins. SF and BFF demonstrated high %M. SL was significantly higher in SF, whereas SP was lowest in BFF after CP treatment. No significant alterations in surface morphology were noted in the BF composites. The BF composites showed a decrease in their properties after immersion in the two types of mouthrinses or in DW, without alterations in the surface morphology. CLINICAL SIGNIFICANCE: Flowable bulk-fill composites showed the greatest changes in their properties when exposed to different mouthrinses or water. Thus, they should be used with caution in areas that will stay exposed to the oral cavity.


Assuntos
Resinas Compostas , Teste de Materiais , Solubilidade
17.
Eur J Pharm Biopharm ; 145: 113-120, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31682903

RESUMO

Lipid-based drug delivery systems (LBDDS) are highly relevant as pharmaceutical formulations significantly enhancing the bioavailability of active pharmaceutical ingredients (APIs). These formulations often are complex mixtures of APIs, various lipids, and other excipients (e.g. surfactants). In their simplest form, LBDDS contain one API being dissolved in a pure lipid, which often is a triglyceride (TG). In this work, solubilities of the APIs indomethacin, ibuprofen, and fenofibrate in pure TGs of different chain lengths (C chain 8-18) and degree of saturation were investigated. Solubilities of APIs in TGs were measured via differential scanning calorimetry, hot-stage microscopy, high-performance liquid chromatography, and Raman spectroscopy. The influence of fatty-acid chain length and degree of saturation on the API solubility in the TGs was investigated. APIs showed a higher solubility in saturated (wIBU = 10.5 wt% at 25 °C in tricaprylin) TGs compared to unsaturated ones (wIBU = 4.0 wt% at 25 °C in triolein). The fatty-acid chain length of TGs only slightly affects the solubility of ibuprofen and fenofibrate, but strongly influences the eutectic temperature of the API/TG mixtures. API solubilities in TGs and TG mixtures (mixtures of tricaprylin and tricaprin) were successfully modeled using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) accounting for the intermolecular API/TG interactions providing a deep understanding of the energetic and structural impact of the TGs on API solubility.


Assuntos
Preparações Farmacêuticas/química , Solubilidade/efeitos dos fármacos , Triglicerídeos/química , Varredura Diferencial de Calorimetria/métodos , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Excipientes/química , Fenofibrato/química , Ibuprofeno/química , Indometacina/química , Lipídeos/química
18.
Phys Chem Chem Phys ; 21(46): 25707-25719, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31720635

RESUMO

To prevent irreversible damage caused by an excess of incident light, the photosynthetic machinery of many cyanobacteria uniquely utilizes the water-soluble orange carotenoid protein (OCP) containing a single keto-carotenoid molecule. This molecule is non-covalently embedded into the two OCP domains which are interconnected by a flexible linker. The phenomenon of OCP photoactivation, causing significant changes in carotenoid absorption in the orange and red form of OCP, is currently being thoroughly studied. Numerous additional spectral forms of natural and synthetic OCP-like proteins have been unearthed. The optical properties of carotenoids are strongly determined by the interaction of their electronic states with vibrational modes, the surrounding protein matrix, and the solvent. In this work, the effects of the pigment-protein interaction and vibrational relaxation in OCP were studied by computational simulation of linear absorption. Taking into account Raman spectroscopy data and applying the multimode Brownian oscillator model as well as the cumulant expansion technique, we have calculated a set of characteristic microparameters sufficient to demarcate different carotenoid states in OCP forms, using the model carotenoids spheroidene and spheroidenone in methanol/acetone solution as benchmarks. The most crucial microparameters, which determine the effect of solvent and protein environment, are the Huang-Rhys factors and the frequencies of C[double bond, length as m-dash]C and C-C stretching modes, the low-frequency mode and the FWHM due to inhomogeneous line broadening. Considering the difference of linear absorption between spheroidene and spheroidenone, which remarkably resembles the photoinduced changes of OCP absorption, and applying quantum chemical calculations, we discuss structural and functional determinants of carotenoid binding proteins.


Assuntos
Proteínas de Bactérias/química , Carotenoides/química , Simulação de Dinâmica Molecular , Teoria Quântica , Água/química , Estrutura Molecular , Solubilidade
19.
Eur J Pharm Biopharm ; 145: 12-26, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31622652

RESUMO

A major shortcoming of drug nanocomposites as compared with amorphous solid dispersions (ASDs) is their limited supersaturation capability in dissolution media. Here, we prepared drug hybrid nanocrystal-amorphous solid dispersions (HyNASDs) and compare their performance to ASDs. A wet-milled griseofulvin (GF, BCS II drug) nanosuspension and a GF solution, both containing the same dissolved polymer-surfactant (SDS: sodium dodecyl sulfate) with 1:1 and 1:3 GF:polymer mass ratios, were spray-dried. Hydroxypropyl cellulose (HPC) and Soluplus (Sol) were used as matrix-forming polymers. XRPD, DSC, and Raman spectroscopy reveal that ASDs were formed upon spray-drying the solution-based feed, whereas nanocomposites and nanocomposites with >10% amorphous content, HyNASDs, were formed with the nanosuspension-based feed. Sol provided higher GF relative supersaturation, up to 180% and 360% for HyNASDs and ASDs, respectively, in the dissolution tests than HPC (up to 50% for both) owing to Sol's stronger intermolecular interactions and miscibility with GF and its recrystallization inhibition. Besides the higher kinetic solubility of GF in Sol, presence of GF nanoparticles vs. micron-sized particles in the nanocomposites enabled fast supersaturation. This study demonstrates successful preparation of fast supersaturating (190% within 20 min) HyNASDs, which renders nanoparticle formulations competitive to ASDs in bioavailability enhancement of poorly soluble drugs.


Assuntos
Liberação Controlada de Fármacos/efeitos dos fármacos , Griseofulvina/química , Nanopartículas/química , Celulose/análogos & derivados , Celulose/química , Cristalização/métodos , Composição de Medicamentos/métodos , Nanocompostos/química , Tamanho da Partícula , Polietilenoglicóis/química , Polímeros/química , Polivinil/química , Dodecilsulfato de Sódio/química , Solubilidade , Tensoativos/química , Suspensões/química
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