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1.
PLoS One ; 15(8): e0237478, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853208

RESUMO

Paclitaxel as a microtubule-stabilizing agent is widely used for the treatment of a vast range of cancers. Corylus avellana cell suspension culture (CSC) is a promising strategy for paclitaxel production. Elicitation of paclitaxel biosynthesis pathway is a key approach for improving its production in cell culture. However, optimization of this process is time-consuming and costly. Modeling of paclitaxel elicitation process can be helpful to predict the optimal condition for its high production in cell culture. The objective of this study was modeling and forecasting paclitaxel biosynthesis in C. avellana cell culture responding cell extract (CE), culture filtrate (CF) and cell wall (CW) derived from endophytic fungus, either individually or combined treatment with methyl-ß-cyclodextrin (MBCD), based on four input variables including concentration levels of fungal elicitors and MBCD, elicitor adding day and CSC harvesting time, using adaptive neuro-fuzzy inference system (ANFIS) and multiple regression methods. The results displayed a higher accuracy of ANFIS models (0.94-0.97) as compared to regression models (0.16-0.54). The great accordance between the predicted and observed values of paclitaxel biosynthesis for both training and testing subsets support excellent performance of developed ANFIS models. Optimization process of developed ANFIS models with genetic algorithm (GA) showed that optimal MBCD (47.65 mM) and CW (2.77% (v/v)) concentration levels, elicitor adding day (16) and CSC harvesting time (139 h and 41 min after elicitation) can lead to highest paclitaxel biosynthesis (427.92 µg l-1). The validation experiment showed that ANFIS-GA method can be a promising tool for selecting the optimal conditions for maximum paclitaxel biosynthesis, as a case study.


Assuntos
Técnicas de Cultura de Células/métodos , Corylus/química , Paclitaxel/biossíntese , Algoritmos , Corylus/metabolismo , Fungos/química , Fungos/metabolismo , Modelos Lineares , Células Vegetais/química , Células Vegetais/metabolismo , beta-Ciclodextrinas/química
2.
J Chromatogr A ; 1626: 461341, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32797822

RESUMO

The recognition and separation of polar chiral compounds are important technological challenges in separation science. Taking full advantage of the intrinsically chiral environment and multiple interactions featured by macrocycles, we designed the first example of porous methylated cyclodextrins-containing polymers (MP-CDPs) with three-dimensional (3D) chiral channels. The enantioselective recognition of (R)/(S)-1-phenylethylamine mixtures was realized with enantiomer excess (e.e.) >73% in only 3 min by using MP-CDPs as the adsorbent. The obtained MP-CDPs also serve as highly efficient liquid chromatographic stationary phases for separation of polar chiral compounds. The stationary phase can separate racemic alcohols and acids successfully. These chiral compounds can be separated within 8 min under normal-phase mode, and the resolution (RS) range from 1.76 to 3.00. Molecular simulations suggest that chiral recognition is a cooperative interaction based on multiple effects such as host-guest interaction, H-bond and size selection. These findings will provide novel chiral stationary phases for recognition and separation of polar chiral compounds in the fields of separation science and pharmaceutical industry.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Polímeros/química , beta-Ciclodextrinas/química , Álcoois/química , Ligação de Hidrogênio , Porosidade , Estereoisomerismo
3.
J Chromatogr A ; 1625: 461332, 2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32709358

RESUMO

Two structural isomeric pentacyclic triterpenes, oleanolic acid and ursolic acid, were considered as the models for the quality control of many traditional Chinese herbal medicines and they have been proved to own important pharmacological activities. In the present work, liquid chromatographic and liquid-liquid chromatographic separation with high peak resolution of structural isomeric oleanolic acid and ursolic acid using hydroxypropyl-ß-cyclodextrin as mobile phase additive was successfully achieved, respectively. A high peak resolution, RS=8.143, was achieved for the two structural isomeric compounds by conventional reverse phase high performance liquid chromatography, which was greatly improved compared with the published values. Meanwhile, a biphasic solvent system composed of n-hexane-ethyl acetate-0.1 mol/L hydroxypropyl-ß-cyclodextrin (9:1:10, v/v) was selected for liquid-liquid chromatography, which provided a high peak resolution, RS = 6.573, for analytical apparatus and Rs = 8.500 for semi-preparative apparatus after optimization by liquid-liquid extractions. Two elution modes including reverse phase mode and normal phase mode were investigated for preparative separation of two acids from crude exact of Eriobotrya japonica Thunb. Furthermore, the inclusion complex between each of the two structural isomers and hydroxypropyl-ß-cyclodextrin were also investigated for high performance liquid chromatography and liquid-liquid chromatography, respectively, in which formation constants were determined for oleanolic acid and ursolic acid.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Cromatografia Líquida/métodos , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Triterpenos/química , Triterpenos/isolamento & purificação , Cromatografia de Fase Reversa , Eriobotrya/química , Isomerismo , Solventes , Temperatura , Termodinâmica , beta-Ciclodextrinas/química
4.
Food Chem ; 333: 127534, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32673948

RESUMO

A new kind of multi-component membrane was prepared by combining gelatin solution, porogen and an inclusion complex of ionic liquid (IL) and beta-cyclodextrin (ß-CD) in a simple physical manner for selective separation of tea polyphenols (TPs) from green tea crude extracts. After screening, it was found that the resulting membrane containing the IL of dicationic N-vinylimidazole proline salt ([VIm]2C3[l-pro]2) had the excellent performance for the enrichment of the target molecules. Then the newly-developed film was comprehensively characterized by scanning electron microscopy, conductivity, thermogravimetry and spectral analysis. Under pressure driving, the adsorption from an aqueous solution of a mixture of TPs and theophylline on IL@ß-CD-Gel membrane showed that the adsorption capacity for TPs was 303.45 mg/g with removal percentages of 94.38%. The experimental data fit well with pseudo-second-order model and Freundlich model. By using this composite material, a new technology of membrane separation for selective adsorption of TPs was finally established.


Assuntos
Fracionamento Químico/métodos , Gelatina/química , Líquidos Iônicos/química , Membranas Artificiais , Polifenóis/isolamento & purificação , Chá/química , beta-Ciclodextrinas/química , Polifenóis/análise
5.
AAPS PharmSciTech ; 21(5): 163, 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32488738

RESUMO

The aim of this study was to evaluate a multicomponent complex (MC) between rifampicin (RIF), ß-cyclodextrin (ß-CD), and selected amino acids to enhance the solubility and antibiofilm activity of RIF. After performing phase-solubility studies that demonstrated a considerable increase in the solubility of RIF for the MC, the corresponding solid system was prepared by a freeze-drying method. Characterization of the MC was performed by Fourier transform-infrared spectroscopy, thermal analysis, powder X-ray diffraction, and scanning electron microscopy. Structural analyses evidenced molecular interactions between the components, resulting in a MC with amorphous solid features. Structural studies involving both experimental (i.e., 1H NMR) and theoretical (i.e., molecular modeling) methodologies demonstrated the inclusion of the RIF piperazine ring in the ß-CD cavity. The bioactivity of the MC measured against biofilms of Staphylococcus aureus showed a significant reduction in the metabolic activity of the bacterium. Overall, the studied MC exhibited promising properties for the development of pharmaceutical formulations to treat bacterial infections.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Rifampina/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/química , Varredura Diferencial de Calorimetria , Composição de Medicamentos , Liofilização/métodos , Microscopia Eletrônica de Varredura , Pós , Rifampina/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X , beta-Ciclodextrinas/química
6.
Ecotoxicol Environ Saf ; 200: 110780, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32470683

RESUMO

A green synthesis method for nanoscale silver using ß-cyclodextrin as both reducing agent and stabilizer was developed. ß-cyclodextrin was used not only as a reducing agent but also a stabilizing agent for nano-silver, and is also an excellent detection substrate due to its special structure (inner hydrophobic and outer hydrophilic ring structure). Then, the green synthesized silver nanoparticles were used as Surface-enhanced Raman spectroscopy (SERS) enhanced substrates to detect polycyclic aromatic hydrocarbons, such as: anthracene, pyrene, chrysene and triphenylene. The SERS substrate can be used for both quantitative detection of the four polycyclic aromatic hydrocarbons and qualitative identification of mixtures of these hydrocarbons. This synthesis method is simple and convenient, having great potential in simultaneous and rapid detection of environmental organic pollutants.


Assuntos
Química Verde/métodos , Nanopartículas Metálicas/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Prata/química , Análise Espectral Raman/métodos , beta-Ciclodextrinas/química , Antracenos/análise , Crisenos/análise , Interações Hidrofóbicas e Hidrofílicas , Pirenos/análise
7.
Soft Matter ; 16(21): 4990-4998, 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32436559

RESUMO

We have identified the hierarchical (primary, secondary, tertiary and quaternary) structures of a polypseudorotaxane (PPR) gel composed of the Pluronic F108 and ß-cyclodextrin system to be ß-cyclodextrin crystalline, lamellar sheets, lamellar stacks and "grains", respectively. The correlation between the rheological properties and the proposed structures under shear flows was rationalized. Alignment of lamellar stacks and reorganization of grain boundaries under shear flows were investigated by rheo-SANS, small angle X-ray scattering and small-angle light scattering. The relaxation of highly aligned lamellar stacks is slow (>2 h) after flow cessation compared to that of the regrouped grains (a few minutes). The main contribution to thixotropic behavior is likely from the faster relaxation of the reorganized grains containing highly oriented lamellar stacks. The comprehensive understanding of structure-function relationship of the PPR gel will facilitate the rational design for its applications.


Assuntos
Hidrogéis/química , Poloxâmero/química , Rotaxanos/química , beta-Ciclodextrinas/química , Reologia
8.
AAPS PharmSciTech ; 21(5): 145, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32430787

RESUMO

The present study demonstrates the solubility and dissolution of flufenamic acid (FLF)/ß-cyclodextrin (ß-CD)/Soluplus® supramolecular ternary inclusion complex. The binary and ternary inclusion complexes were prepared using solvent evaporation and the microwave irradiation method. The prepared inclusion complexes were evaluated for physicochemical characterization and anti-inflammatory activity using a murine paw edema mol. The phase solubility studies demonstrated 4.59-fold and 17.54-fold enhancements in FLF solubility with ß-CD alone and ß-CD:Soluplus® combination compared with pure FLF, respectively. The in vitro drug release results revealed a significant improvement (P < 0.05) in the release pattern compared with pure FLF. Maximum release was found with flufenamic acid binary and ternary complexes prepared using the microwave irradiation method, i.e., 75.23 ± 3.12% and 95.36 ± 3.23% in 60 min, respectively. The physicochemical characterization results showed complex formation and conversion of the crystalline form of FLF to an amorphous form. The SEM study revealed the presence of a more agglomerated and amorphous structure of the solid particles, which confirmed the formation of complexes. The anti-inflammatory effect of the complex was higher than pure FLF. Therefore, the FLF:ß-CD:Soluplus® inclusion complex may be a very valuable formulation with improved solubility, dissolution, and anti-inflammatory effect.


Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Ácido Flufenâmico/química , Ácido Flufenâmico/farmacologia , Polietilenoglicóis/química , Polivinil/química , beta-Ciclodextrinas/química , Animais , Varredura Diferencial de Calorimetria , Carragenina , Cristalização , Composição de Medicamentos , Edema/induzido quimicamente , Edema/patologia , Excipientes , Masculino , Micro-Ondas , Ratos , Ratos Wistar , Solubilidade , beta-Ciclodextrinas/farmacologia
9.
Int J Nanomedicine ; 15: 2515-2527, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368038

RESUMO

Purpose: Reactive oxygen species (ROS)-induced oxidative stress plays a key role in the pathogenesis and progression of psoriasis by causing inflammation. Antioxidative strategies eradicating ROS may serve as effective and easy treatment options for psoriasis, while nanozymes with intrinsic antioxidant enzyme-like activity have not been explored for psoriasis treatment. The aim of this study is to fabricate ß-cyclodextrins (ß-CDs)-modified ceria nanoparticles (ß-CDs/CeO2 NPs) with drug-loaded and multimimic-enzyme activities for combinational psoriasis therapy. Methods: The ß-CDs/CeO2 NPs were synthesized by a hydrothermal method using unmodified ß-CDs as a protecting agent. The structure, size and morphology were analyzed by dynamic light scattering, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy. Considering the superoxide dismutase (SOD)- and catalase-mimetic activities, the in vitro antioxidant activity of the ß-CDs/CeO2 NPs was investigated. After dithranol (DIT) was loaded, the drug-loading capacity and release profile were determined by UV-visible light spectrophotometer and high-performance liquid chromatography. The anti-psoriatic efficacy was studied in the imiquimod (IMQ)-induced mouse model on the basis of morphological evaluation, psoriasis area and severity index calculation (PASI), and inflammatory cytokine expression. Results: The average particle size of the blank ß-CDs/CeO2 NPs was 60.89±0.32 nm with a polydispersity index (PDI) of 0.12, whereas that of the DIT-loaded NPs was 79.38±1.06 nm with a PDI of 0.27. TEM results showed the as-prepared NPs formed a uniform quasi-spherical shape with low polydispersity. XPS indicates synthesized NPs have a mixed Ce3+/Ce4+ valence state. FTIR spectroscopy confirmed the presence of ß-CDs and DIT in the NPs. Inhibition of superoxide anion rate by NPs could be reached to 79.4% in the presence of 200 µg/mL, and elimination of H2O2 efficiency reached about 50% in the presence of 40 µg/mL, demonstrating excellent superoxide dismutase- and catalase-mimicking activities, thereby providing remarkable cryoprotection against ROS-mediated damage. Furthermore, ß-CDs on the surface endowed the NPs with drug-loading function via host-guest interactions. The entrapment efficiency and drug loading of DIT are 94.7% and 3.48%, respectively. The in vitro drug release curves revealed a suitable release capability of DIT@ß-CDs/CeO2 NPs under physiological conditions. In IMQ-induced psoriatic model, the DIT@ß-CDs/CeO2 NPs exhibited excellent therapeutic effect. Conclusion: This study may pave the way for the application of nanozyme ß-CDs/CeO2 NPs as a powerful tool for psoriasis therapy.


Assuntos
Cério/química , Nanopartículas/química , Psoríase/terapia , beta-Ciclodextrinas/química , Animais , Catalase/metabolismo , Linhagem Celular , Sobrevivência Celular , Terapia Combinada , Depuradores de Radicais Livres/química , Hidrodinâmica , Imiquimode/farmacologia , Imiquimode/uso terapêutico , Masculino , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Tamanho da Partícula , Espectroscopia Fotoeletrônica , Psoríase/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Pele/efeitos dos fármacos , Pele/patologia , Espectroscopia de Infravermelho com Transformada de Fourier , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , beta-Ciclodextrinas/síntese química
10.
J Chromatogr A ; 1622: 461128, 2020 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-32331779

RESUMO

We present high resolution fast, cost-effective and sensitive Capillary zone electrophoresis (CZE) methods for determination of enantiomeric compounds of Kynurenine pathway, i.e. D, L-Kynurenine (KYN), in human serum and urine samples by cationic-ß-CD and its synergistic dual chiral selector system (SD-CSs) with α-CD in 50 mM borax borate buffer (pH 9.0) as BGE. Acid-mediated stacking enrichment by HCl delivered 15 nM limit of detection (LOD) and 50 nM limit of quantification (LOQ). The methods gave advantages of linearity in the concentration range of 50 nM-1000 nM, reproducibility (RSD ≤ 3.35), selectivity against interfering amino acids, and remarkable recoveries. SD-CSs delivered resolution of D, L-KYN twice that of individual chiral selectors (CSs) under similar conditions. The binding constants (Kb) and electrophoretic mobilities (µeff) of D, L-KYN with different concentrations of CSs were calculated to find the migration order of enantiomers. The chiral recognition mechanism was investigated by molecular docking and molecular mechanics, which revealed strong hydrogen bonding between Kynurenine enantiomers and the SD-CSs as compared to individual CS as the key player in binding, formation of stable complexes which led to the ultimate separation.


Assuntos
Eletroforese Capilar/métodos , Cinurenina/química , alfa-Ciclodextrinas/química , beta-Ciclodextrinas/química , Aminoácidos/química , Tampões (Química) , Cátions , Humanos , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Cinética , Cinurenina/sangue , Cinurenina/isolamento & purificação , Cinurenina/urina , Limite de Detecção , Simulação de Acoplamento Molecular , Estereoisomerismo
11.
Food Chem ; 321: 126750, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32278273

RESUMO

This work investigated the interaction between cyclodextrins and pullulanase to provide insight into the production and application of cyclodextrins. Enzyme activity and kinetic assays showed that α-cyclodextrin (α-CD), ß-cyclodextrin (ß-CD) and γ-cyclodextrin (γ-CD) inhibited pullulanase in a competitive manner. Circular dichroism spectra and fluorescence spectroscopy suggested the formation of cyclodextrin and pullulanase complexes. According to ITC assays and molecular docking results, compared with α-CD and γ-CD, ß-CD had the strongest affinity for pullulanase because of its appropriate cavity geometric dimensions. In addition, cyclodextrins interacted with pullulanase through hydrogen bonds, van der Waals force and hydrophobic interactions, the latter of which were verified as the major driving force. Phenylalanine 476 was the key amino acid residue in pullulanase for cyclodextrin recognition and binding.


Assuntos
Ciclodextrinas/química , Ciclodextrinas/metabolismo , Glicosídeo Hidrolases/química , Glicosídeo Hidrolases/metabolismo , Calorimetria/métodos , Dicroísmo Circular , Glicosídeo Hidrolases/antagonistas & inibidores , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Fenilalanina/metabolismo , Estrutura Secundária de Proteína , Espectrometria de Fluorescência , alfa-Ciclodextrinas/química , alfa-Ciclodextrinas/metabolismo , beta-Ciclodextrinas/química , beta-Ciclodextrinas/metabolismo , gama-Ciclodextrinas/química , gama-Ciclodextrinas/metabolismo
12.
Food Chem ; 320: 126655, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32224423

RESUMO

The effects of ß-cyclodextrin (ß-CD), whey protein (WP), and soy protein (SP) on the color loss and degradation of anthocyanins in purple-fleshed sweet potato anthocyanin extracts (PFSPAEs) during thermal treatment and shelf-life storage in model beverage systems by performing chromaticity, degradation kinetics, and principal component analysis. Results showed that WP and SP improved the thermal stability of the PFSPAE, but WP accelerated the color loss of the extract. However, the addition of 25 mg/L SP improved the color and thermal stability of the anthocyanins when heated at 100 °C for 30 min. With regard to the shelf-life storage, the addition of SP and WP showed non-significant effect on the storage stability of the PFSPAE. However, the addition of 2500 mg/L ß-CD significantly improved the storage stability of the PFSPAE. In summary, our findings provide useful information on improving the thermal and storage stability of PFSPAEs in beverage systems using food biopolymers.


Assuntos
Antocianinas/química , Ipomoea batatas/química , Proteínas de Soja/química , Proteínas do Soro do Leite/química , beta-Ciclodextrinas/química , Antocianinas/análise , Bebidas , Armazenamento de Alimentos , Temperatura Alta
13.
Food Chem ; 321: 126686, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32247182

RESUMO

Impacts of 2-butanol and ß-cyclodextrin (ß-CD) at various ratios and treatment times on bitterness, physicochemical and functional properties of Alcalase salmon frame protein hydrolysate (ASF) were investigated. ASF treated with 2-butanol at a ratio of 1:4 (w/v) for 20 min (ASFB) or with ß-CD at a ratio of 1:1 (w/w) for 30 min (ASF-C-1) had lower bitterness score than ASF (p < 0.05). Bitterness score of ASF (8.45) was reduced to the lowest score (1.32) when ASFB was subsequently treated with ß-CD at a 1:1 ratio (w/w) for 30 min (ASFB-C-1). Surface hydrophobicity of all debittered samples was lower than that of ASF sample (p < 0.05). The level of aromatic amino acids-containing peptides was reduced in ASFB-C-1 as shown by gel permeation chromatography. ASFB-C-1 sample had higher overall-likeness score but lower antioxidant properties than ASF (p < 0.05). The desired antioxidant activity could be achieved via increasing the amount of protein hydrolysate without imparting undesirable taste.


Assuntos
Antioxidantes/química , Proteínas de Peixes da Dieta/química , Salmo salar , Subtilisinas/química , beta-Ciclodextrinas/química , Animais , Butanóis/química , Proteínas de Peixes da Dieta/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Peptídeos/química , Salmo salar/metabolismo , Alimentos Marinhos , Subtilisinas/metabolismo , Paladar
14.
Chemosphere ; 250: 126250, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32234618

RESUMO

Presence of even small amount of active pharmaceutical ingredients in the environment carries risks to human and animal health, presenting an important issue. The paper presents issues related to the new drug - pimavanserin (PMV). Biological treatment efficiency of pimavanserin (PMV) was evaluated using lab-scale Sequencing Batch Reactor (SBR). It has been shown to have a negative effect on aquatic organisms by classifying it as a toxic compound (EC50 = 8 mgL-1). The level of biological degradation of PMV was insufficient (37%) and intensively foam formation caused operational problems. For this reason, in this study polymers based on cyclodextrins (CDs) were synthesized and used as adsorbents alternative to active carbons to effectively separate PMV from real industrial waste streams. Crosslinked ß- and γ-CD polymers (ß- and γ-NS), obtained in reaction with 1,1'-carbonyldiimidazole (CDI), were fully characterized by physicochemical methods. The adsorption equilibrium data were interpreted using Freundlich and Langmuir models. The sorption process was fast (60 s) and the efficiency of PMV separation from model waste waters was 93% and 81% for ß- and γ-NS, respectively. Maximum polymer capacity was found at 52.08 mg g-1 for ß-NS and 23.26 mg g-1 for γ-NS. The interactions of PMV with CDs have been studied and indicate that major mechanism of the sorption is based on supramolecular interaction and capture to polymer network. Described biodegradable and reusable materials are perfect example of correctly selected adsorbent for separation of target substance from postproduction aqueous media.


Assuntos
Piperidinas/química , Ureia/análogos & derivados , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Adsorção , Celulose/química , Ciclodextrinas/química , Resíduos Industriais , Preparações Farmacêuticas , Polímeros/química , Ureia/química , Águas Residuárias , beta-Ciclodextrinas/química
15.
Nat Commun ; 11(1): 2045, 2020 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-32341352

RESUMO

Current approaches for nanomaterial delivery in plants are unable to target specific subcellular compartments with high precision, limiting our ability to engineer plant function. We demonstrate a nanoscale platform that targets and delivers nanomaterials with biochemicals to plant photosynthetic organelles (chloroplasts) using a guiding peptide recognition motif. Quantum dot (QD) fluorescence emission in a low background window allows confocal microscopy imaging and quantitative detection by elemental analysis in plant cells and organelles. QD functionalization with ß-cyclodextrin molecular baskets enables loading and delivery of diverse chemicals, and nanoparticle coating with a rationally designed and conserved guiding peptide targets their delivery to chloroplasts. Peptide biorecognition provides high delivery efficiency and specificity of QD with chemical cargoes to chloroplasts in plant cells in vivo (74.6 ± 10.8%) and more specific tunable changes of chloroplast redox function than chemicals alone. Targeted delivery of nanomaterials with chemical cargoes guided by biorecognition motifs has a broad range of nanotechnology applications in plant biology and bioengineering, nanoparticle-plant interactions, and nano-enabled agriculture.


Assuntos
Cloroplastos/química , Nanoestruturas/química , Plantas/química , Arabidopsis/química , Sítios de Ligação , Cinética , Microscopia Confocal , Microscopia de Fluorescência , Nanopartículas , Nanotecnologia , Oxirredução , Peptídeos/química , Fotossíntese , Folhas de Planta/química , Pontos Quânticos , Termodinâmica , beta-Ciclodextrinas/química
16.
Cancer Sci ; 111(5): 1794-1804, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32154964

RESUMO

Folate receptor alpha (FRα) is overexpressed in >80% of epithelial ovarian cancer (EOC). Accordingly, folate is attracting attention as a targeting ligand for EOC. For EOC patients, paclitaxel (PTX) is generally used as a first-line chemotherapeutic agent in combination with platinum-based drugs. Cyclodextrin (CyD) is a potential new formulation vehicle for PTX that could replace Cremophor-EL, a traditional formulation vehicle that causes significant side effects, including neutropenia. Several years ago, folate-appended ß-CyD (Fol-c1 -ß-CyD) was developed as an FRα-targeting drug carrier, but its efficacy as a treatment for EOC remains to be determined. In this study, we assessed the antitumor activity of PTX in Fol-c1 -ß-CyD (PTX/Fol-c1 -ß-CyD) in EOC-derived cell lines. We found that PTX/Fol-c1 -ß-CyD killed not only FRα-expressing cells but also FRα-negative cells. In the FRα-negative A2780 cells, knockdown of proton-coupled folate transporter (PCFT) significantly decreased the cytotoxicity of PTX/Fol-c1 -ß-CyD, whereas knockdown of FRα did not. By contrast, knockdown of either FRα or proton-coupled folate transporter (PCFT) decreased the cytotoxicity of PTX/Fol-c1 -ß-CyD in FRα-expressing SK-OV-3 cells. Furthermore, the cytotoxicity of PTX/Fol-c1 -ß-CyD in A2780 cells was increased at acidic pH, and this increase was suppressed by PCFT inhibitor. In mice intraperitoneally inoculated with FRα-expressing or PCFT-expressing EOC cells, intraperitoneal administration of PTX/Fol-c1 -ß-CyD significantly suppressed the growth of both types of EOC cells relative to PTX alone, without inducing a significant change in the neutrophil/white blood cell ratio. Our data suggest that Fol-c1 -ß-CyD targets not only FRα but also PCFT, and can efficiently deliver anticancer drugs to EOC cells in the peritoneal cavity.


Assuntos
Carcinoma Epitelial do Ovário/metabolismo , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Ácido Fólico/química , Neoplasias Ovarianas/metabolismo , Transportador de Folato Acoplado a Próton/metabolismo , beta-Ciclodextrinas/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/administração & dosagem , Feminino , Receptor 1 de Folato/genética , Receptor 1 de Folato/metabolismo , Ácido Fólico/administração & dosagem , Expressão Gênica , Humanos , Camundongos , Estrutura Molecular , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Paclitaxel/química , Paclitaxel/farmacologia , Transportador de Folato Acoplado a Próton/genética , Ensaios Antitumorais Modelo de Xenoenxerto , beta-Ciclodextrinas/administração & dosagem
17.
J Chromatogr A ; 1619: 460971, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32089289

RESUMO

When cyclodextrins (CDs) are used in chromatography analytes' retention time is decreased with an increase in concentration of CD in the mobile phase. Thus complex stability constants can be determined from the change in retention time of the ligand molecule upon complexation. Since the preceding approach implies extensive and time-consuming HPLC experiments, the goal of this research was to investigate the possibility of using in silico prediction tools instead. Quantitative structure-retention relationship (QSRR) model previously developed to explain the retention behavior of risperidone, olanzapine and their structurally related impurities in ß-CD modified HPLC system was applied to predict retention factor under different chromatographic conditions within the examined domains. Predicted retention factors were further used for calculation of stability constants and important thermodynamic parameters, namely standard Gibbs free energy, standard molar enthalpy and entropy, contributing to inclusion phenomenon. Unexpected prolonged retention with an increase in ß-CD concentration was observed, in contrast to the employed chromatographic theory used for the calculation of the stability constants. Consequently, it led to failure in stability constants and thermodynamic parameters calculation for almost all analytes when acetonitrile content was 20% (v/v) across the investigated pH range. Moreover, ionization of investigated analytes and free stationary phase silanol groups are pH dependent, leading to minimization of secondary interactions if free silanol groups are non-ionized at pH lower than 3. In order to prove accuracy of predicted retention factors, HPLC verification experiments were performed and good agreement between predicted and experimental values was obtained, confirming the applicability of proposed in-silico tool. However, the obtained results opened some novel questions and revealed that chromatographic method is not overall applicable in calculation of stability constants and thermodynamic parameters indicating the complexity of ß-CD modified systems.


Assuntos
Cromatografia Líquida de Alta Pressão , Modelos Teóricos , beta-Ciclodextrinas/química , Acetonitrilos/química , Entropia , Termodinâmica
18.
J Chromatogr A ; 1620: 460932, 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32029266

RESUMO

Although various cyclodextrins (CDs) have been utilized to prepare organic polymer-based monolithic columns, there were few reports on fabrication of cyclodextrin functionalized hybrid monolithic columns. Herein, a sulfobutylether ß-cyclodextrin (SBE-ß-CD)-silica hybrid monolithic column was prepared by "one-step" method via the co-polymerization of hydrolyzed organosiloxane precursors and glycidyl methacrylate-sulfobutylether ß-cyclodextrin (GMA-SBE-ß-CD). The morphologies of prepared monolithic columns were observed by optical microscopy and scanning electron microscopy (SEM). The sulfobutylether ß-cyclodextrin was incorporated into the polymeric structure, which was demonstrated by energy dispersive X-ray spectroscopy (EDS), Fourier-transform infrared spectroscopy (FTIR) spectrum and X-ray photoelectron spectroscopy (XPS). The resulting columns were used for chiral separations of twenty six racemic compounds, and satisfactory separation selectivity was obtained. Compared with other two kinds of neutral cyclodextrin (ß-CD and HP-ß-CD) based hybrid monoliths, sulfobutylether ß-cyclodextrin-silica hybrid monolith showed superior chiral resolution. These results demonstrated the sulfobutylether ß-cyclodextrin-silica hybrid monolithic column was promising in chiral compounds analysis.


Assuntos
Eletrocromatografia Capilar , Dióxido de Silício/química , beta-Ciclodextrinas/química , 2-Hidroxipropil-beta-Ciclodextrina/química , Compostos de Epóxi/química , Metacrilatos/química , Microscopia Eletrônica de Varredura , Espectroscopia Fotoeletrônica , Polimerização , Polímeros/química , Estereoisomerismo
19.
Food Chem ; 316: 126280, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32058192

RESUMO

Green pepper (Piper nigrum) presents high levels of functional compounds, with antioxidant and anti-glycation properties. Thus, the optimization of the ß-cyclodextrin-based extraction of functional compounds from green pepper through Response Surface Methodology was performed. The optimum extraction conditions were assessed by optimizing total polyphenolic content (TPC) and antioxidant activity (DPPH• and FRAP methods). 15 mM for ß-CD solution, 5 min of ultrasonication and 41 °C were the optimum extraction conditions, with the TPC of 24.9 mg GAE/mL and the anti-radical activities were 3.1 mg GAE/mL (DPPH• assay) and 0.45 mg GAE/mL (FRAP method). This natural extract obtained through eco-friendly techniques proved to be effective to reduce the formation of hydroxymethylfurfural, a glycation marker, at 70 and 80 °C. GPE presented higher TPC than black and white pepper. The relationship between the antioxidant and anti-glycation properties was confirmed and green pepper and can be proposed as a natural potential anti-glycation agent.


Assuntos
Antioxidantes/química , Piper nigrum/química , Glicosilação , beta-Ciclodextrinas/química
20.
J Chromatogr A ; 1619: 460937, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32063276

RESUMO

An ethylenediamine dicarboxyethyl diacetamido-bridged bis(ß-cyclodextrin) was firstly synthesized through the reaction of 6-deoxy-6-amino-ß-cyclodextrin (NH2-CD) with ethylenediaminetetraacetic dianhydride. Then it was bonded onto the surface of silica gel SBA-15 to obtain an ethylenediamine dicarboxyethyl diacetamido-bridged bis(ß-CD)-bonded chiral stationary phase (EBCDP). The structures of the bridged bis(ß-CD) and EBCDP were characterized by infrared spectroscopy, mass spectrometry, elemental analysis and thermogravimetric analysis, accordingly. The chiral chromatographic performances of EBCDP were systematically evaluated by separating 28 racemic analytes in the reversed-phase or polar organic mode, including eight flavanones, eight bolckers, five dansyl-amino acids, three DL-amino acids and four other common drugs. As a result, the relatively high enantioselectivity of EBCDP was observed in comparison with a native ß-CD-CSP (CDSP). All selected analytes were separated on EBCDP, of which 20 analytes had resolutions up to baseline, 2'-hydroxyflavanone and arotinolol had resolutions up to 4.35 and 2.05 in about 30 min, respectively, whereas CDSP only separated 11 analytes with low resolutions (0.55~1.69). Moreover, EBCDP was able to utilize the complexation of the bridging linker (ethylenediamine dicarboxyethyl diamide group, EDTA-based) to realize direct separations of DL-amino acids with a mobile phase containing copper ion (Cu2+), which was similar to the chiral ligand exchange chromatography. Unlike the native cyclodextrin with small cavity (~242 Å3), the bridged bis(ß-CD) combined two ß-CD units with a bridging linker, having a well-organized "pseudo-cavity" as an organic whole to encapsulate more analytes, which made EBCDP have broad-spectrum applications in chiral separations.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , beta-Ciclodextrinas/química , Aminoácidos/isolamento & purificação , Flavanonas/química , Dióxido de Silício/química , Estereoisomerismo , beta-Ciclodextrinas/síntese química , beta-Ciclodextrinas/normas
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