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1.
Chem Pharm Bull (Tokyo) ; 67(9): 915-920, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474729

RESUMO

Controlling drug crystallization is one of the important issues in pre-formulation study. In recent years, advanced approaches including the use of tailor-made additives have gathered considerable attention to control crystallization behavior of drugs. This review focuses on the use of hydrophilic cyclodextrins (CDs) as additives for controlling drug crystallization. CDs affect the crystallization of drugs in solution and in solid state based on a host-guest interaction. For example, 2,6-di-O-methyl-ß-CD and 2-hydroxybutyl-ß-CD suppressed solution-mediated transition of drugs during crystallization by the host-guest interaction; as a result, metastable forms selectively precipitated in solution. The use of CDs in crystal engineering provided an opportunity for the detection of a new polymorph by changing the crystallization pathway. It was also possible to modify crystal morphology (i.e., crystal habit) by selective suppression of crystal growth on a certain direction based on the host-gust interaction. For solid formulation, stable amorphous drug/CDs complex under humid conditions was prepared using two different CDs. An overview of some recent progress in the use of CDs in crystal engineering and in amorphous formulation is described in this review.


Assuntos
Preparações Farmacêuticas/química , beta-Ciclodextrinas/química , Acetoexamida/química , Aspirina/química , Cristalização , Composição de Medicamentos , Interações Hidrofóbicas e Hidrofílicas
2.
Int J Nanomedicine ; 14: 6481-6495, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496698

RESUMO

Background: Despite the numerous pharmacological activities of quercetin, its biomedical application has been hampered, because of poor water solubility and low oral bioavailability. In the present study, we fabricated a novel form of quercetin-conjugated Fe3O4-ß-cyclodextrin (ßCD) nanoparticles (NPs), and the effect of these prepared NPs was evaluated in a chronic model of epilepsy. Methods: Quercetin-loaded NPs were prepared using an iron oxide core coated with ßCD and pluronic F68 polymer. The chronic model of epilepsy was developed by intraperitoneal injection of pentylenetetrazole (PTZ) at dose of 36.5 mg/kg every second day. Quercetin or its nanoformulation at doses of 25 or 50 mg/kg were administered intraperitoneally 10 days before PTZ injections and their applications continued 1 hour before each PTZ injection. Immunostaining was performed to evaluate the neuronal density and astrocyte activation of hippocampi. Results: Our data showed successful fabrication of quercetin onto Fe3O4-ßCD NPs. In comparison to free quercetin, quercetin NPs markedly reduced seizure behavior, neuronal loss, and astrocyte activation in a PTZ-induced kindling model. Conclusion: Overall, quercetin-Fe3O4-ßCD NPs might be regarded as an ideal therapeutic approach in epilepsy disorder.


Assuntos
Epilepsia/tratamento farmacológico , Nanopartículas de Magnetita/química , Quercetina/uso terapêutico , beta-Ciclodextrinas/química , Animais , Astrócitos/efeitos dos fármacos , Modelos Animais de Doenças , Hipocampo/patologia , Excitação Neurológica , Nanopartículas de Magnetita/administração & dosagem , Nanopartículas de Magnetita/ultraestrutura , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Pentilenotetrazol/administração & dosagem , Quercetina/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier
3.
Chem Biol Interact ; 311: 108774, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31369748

RESUMO

Silica nanoparticles (SiNPs) are one of the popular nanomaterials used in industrial manufacturing, synthesis, engineering, and medicine. Recently, mechanisms underlying toxicity of silica nanoparticles have been reported; however, their uptake mechanisms have still not fully understood. In this study, toxicity of SiNPs was investigated in the nematode Caenohabditis elegans by using microarray and pathway analysis focusing the uptake mechanisms and their impact on toxicity. Physicochemical characterization of SiNPs was performed using dynamic light scattering (DLS) and zeta potential. No mortality was observed after 24 h exposure to SiNPs. However, reproductive ability was significantly reduced at the same concentrations. To ascertain a global mechanism of toxicity, microarray was conducted on C. elegans exposed to 10 mg/L SiNPs (20% reduction in reproductive ability). Microarray results indicated that genes involved in reproduction, such as msp (Major Sperm Protein) genes, were significantly downregulated in C. elegans exposed to SiNPs. Pathway analyses on differentially expressed genes (DEGs) revealed that endocytic pathway as a major pathway involved in the uptake of SiNPs. Involvement of endocytic pathway in the uptake of SiNPs was assessed using specific inhibitors (methyl-ß-cyclodextrin, chlorpromazine, and LY294002 for caveolin-, clathrin-, and pinocytosis-mediated endocytosis, respectively). The inhibitor assay indicated that an internalization process facilitated by clathrin-mediated endocytosis is involved in the uptake of SiNPs. Functional analysis using endocytosis defective mutants, (i,e.  cav-1, cup-2, and chc-1) confirmed the role of endocytosis on the reproductive toxicity of SiNPs. Overall results suggest that clathrin-mediated endocytosis pathway is a potential mechanism of uptake of SiNPs in C. elegans that in turn, affects general toxic outcome, such as, decrease in reproductive ability.


Assuntos
Caenorhabditis elegans/metabolismo , Clatrina/metabolismo , Endocitose/efeitos dos fármacos , Nanopartículas/toxicidade , Dióxido de Silício/química , Animais , Caenorhabditis elegans/crescimento & desenvolvimento , Redes Reguladoras de Genes/efeitos dos fármacos , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Reprodução/efeitos dos fármacos , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacologia
4.
Chem Asian J ; 14(19): 3320-3328, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31407483

RESUMO

The supramolecular complexation of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) with heptakis(2,3,6-tri-O-methyl)-ß-cyclodextrin (TMCD) has been known to be highly specific in aqueous media. In this study, we have used NMR spectroscopy to reveal that this supramolecular system also works even in biologically crowded media such as serum, blood, and urine. A 13 C-labeled heptakis(2,3,6-tri-O-methyl-13 C)-ß-cyclodextrin (13 C-TMCD) was synthesized and studied using one-dimensional (1D) HMQC spectroscopy in serum and blood. The 1D HMQC spectrum of 13 C-TMCD showed clear signals due to the 2-, 3-, and 6-O13 CH3 groups, whose chemical shifts changed upon addition of TPPS due to quantitative formation of the 13 C-TMCD/TPPS=2/1 inclusion complex in such biological media. The 1 H NMR signals of non-isotope-labeled TPPS included by 13 C-TMCD were detected using the 13 C-filtered ROESY technique. A pharmacokinetic study of 13 C-TMCD and its complex with TPPS was carried out in mice using the 1D HMQC method. The results indicated that (1) 1D HMQC is an effective technique for monitoring the inclusion phenomena of 13 C-labeled cyclodextrin in biological media and (2) the intermolecular interaction between 13 C-TMCD and TPPS is highly selective even in contaminated media like blood, serum, and urine.


Assuntos
Porfirinas/química , beta-Ciclodextrinas/química , Animais , Ânions/química , Isótopos de Carbono/química , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Porfirinas/sangue , Porfirinas/urina , beta-Ciclodextrinas/sangue , beta-Ciclodextrinas/urina
5.
Int J Nanomedicine ; 14: 5397-5413, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409995

RESUMO

Background: Hyperlipidemia is the elevation of low density lipoprotein levels resulting in fat deposites in arteries and their hardening and blockage.  It is the leading cause of several life threatening pathological conditions like hypertension, cardiovascular diseases, diabetes etc. Purpose: The objective of this study was to prepare and optimize nontoxic, biocompatible ß-CD-g-MAA/Na+-MMT nanocomposite hydrogels with varying content of polymer, monomer and montmorillonite. Moreover, lipid lowering potentials were determined and compared with other approaches. Methods: ß-CD-g-MAA/Na+-MMT nanocomposite hydrogels (BM-1 to BM9) were prepared through free radical polymerization by using  ß-CD  as polymer, MAA as monomer, MBA as crosslinker and montmorillonite as clay. Developed networks were evaluated for FTIR, DSC, TGA, PXRD, SEM, sol-gel fraction (%), swelling studies, antihyperlipidemic studies and toxicity studies. Results: Optimum swelling (94.24%) and release (93.16%) were obtained at higher pH values. Based on R2 and "n" value LVT release followed zero order kinetics with Super Case II transport release mechanism, respectively. Tensile strength and elongation at break were found to be 0.0283MPa and 94.68%, respectively. Gel fraction was between 80.55 - 98.16%. Antihyperlipidemic studies revealed that LDL levels were markedly reduced from 522.24 ± 21.88mg/dl to 147.63 ± 31.5mg/dl. Toxicity studies assured the safety of developed network. Conclusion: A novel pH responsive crosslinked network containing ß-CD - g - poly (methacrylic acid) polymer and MMT was developed and optimized with excellent mechanical, swelling and release properties and lipid lowering potentials.


Assuntos
Bentonita/química , Hidrogéis/química , Lovastatina/administração & dosagem , Metacrilatos/química , Nanocompostos/química , beta-Ciclodextrinas/química , Acrilamidas/química , Administração Oral , Animais , Varredura Diferencial de Calorimetria , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Cinética , Lipídeos/sangue , Nanocompostos/ultraestrutura , Especificidade de Órgãos , Coelhos , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura Ambiente , Resistência à Tração , Termogravimetria , Testes de Toxicidade Aguda , Difração de Raios X
6.
Chem Commun (Camb) ; 55(67): 9959-9962, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31364996

RESUMO

On the basis of BSA stabilized tetraphenylethylene nanocrystals (BSA-TPE NCs) as aggregation-induced enhanced electrochemiluminescence (ECL) emitters with high ECL efficiency and good biocompatibility, as well as molecular recognition between ß-CD and ferrocene, an ultrasensitive and versatile ECL biosensing platform was constructed to achieve microRNA detection in cancer cells.


Assuntos
Materiais Biocompatíveis/química , Corantes Fluorescentes/química , MicroRNAs/análise , Nanopartículas/química , Soroalbumina Bovina/química , Estilbenos/química , Animais , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Bovinos , Linhagem Celular Tumoral , Técnicas Eletroquímicas , Compostos Ferrosos/química , Humanos , Limite de Detecção , Medições Luminescentes , Metalocenos/química , Sensibilidade e Especificidade , beta-Ciclodextrinas/química
7.
Food Chem ; 300: 125249, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31352291

RESUMO

Under the optimal conditions, a crosslinked electrospun polyvinyl alcohol/cinnamon essential oil/ß-cyclodextrin (CPVA-CEO-ß-CD) nanofibrous films for sustained release of antimicrobials were successfully prepared. Cinnamon essential oil (CEO) can be sustainably released due to CPVA-CEO-ß-CD nanofibers complex delivery systems. The chemical crosslinking and physical welding achieved simultaneously by glutaraldehyde atomization fumigation, making fibers more suitable for fresh food packaging. Nanofibrous films were characterized in terms of SEM, ATR-FTIR, DSC, water contact angle analysis and antibacterial trials. ATR-FTIR and DSC data indicated that CEO was encapsulated in a ß-CD cavity and they coexisted in PVA nanofibers. The water contact angle of the crosslinked PVA nanofibrous films increased with CEO and the values were always below 90°. Crosslinked nanofibers possessed fine properties in vitro antibacterial against Staphylococcus aureus and Escherichia coli. Furthermore, CPVA/ß-CD/CEO nanofibrous films delayed decay of mushroom during storage, indicating their potential implementation in active food packaging.


Assuntos
Agaricales/fisiologia , Embalagem de Alimentos/métodos , Nanofibras/química , Álcool de Polivinil/química , beta-Ciclodextrinas/química , Antibacterianos/química , Antibacterianos/farmacologia , Cinnamomum zeylanicum/química , Reagentes para Ligações Cruzadas/química , Escherichia coli/efeitos dos fármacos , Embalagem de Alimentos/instrumentação , Armazenamento de Alimentos , Glutaral/química , Microscopia Eletrônica de Varredura , Óleos Voláteis/química , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos
8.
Food Chem ; 299: 125119, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31295638

RESUMO

Of all the active compounds in rosemary extract, carnosic acid (CaA) has the most potent antimicrobial and antioxidant activity; however, its low solubility limits its applications. We developed complexing systems using cycloamylose (CA), branched dextrin (BD), and ß-cyclodextrin (ßCD) to improve the solubility of CaA and compared it to the use of maltodextrin (MD). The complexes formed with CA, BD, ßCD, and MD improved the water solubility of CaA by as much as 2.8-fold, 2.1-fold, 1.75-fold, and 2.06-fold, respectively. The antioxidant capacity of CaA in aqueous solutions was also enhanced in the complexes due to the increased water solubility. Interestingly, the antimicrobial activity was improved more dramatically upon complexation with CA (7.27-fold) compared to the improvement when complexed with BD (4.82-fold), ßCD (2.87-fold), and MD (3.83-fold). This may be due to the improvement of the antimicrobial potential of the functional groups of CaA by complexation with flexible cyclic glucans.


Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Diterpenos de Abietano/farmacologia , Conservantes de Alimentos/farmacologia , Extratos Vegetais/farmacologia , Rosmarinus/química , Ciclodextrinas/química , Aditivos Alimentares , Depuradores de Radicais Livres/farmacologia , Glucanos/química , Extratos Vegetais/isolamento & purificação , Polissacarídeos/química , Solubilidade/efeitos dos fármacos , beta-Ciclodextrinas/química
9.
AAPS PharmSciTech ; 20(6): 244, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286296

RESUMO

Cyclodextrin (CD) inclusions are generally used to increase the solubility of poorly soluble drugs. In this study, magnolol (MAG) was used as a model drug for exploring the effects of CD on the degradation of pharmaceutical drugs by intestinal microflora. MAG/ß-cyclodextrin (ß-CD) and MAG/hydroxypropyl-ß-CD (HP-ß-CD) inclusion complexes were successfully prepared by the saturated aqueous solution and freeze-drying methods, respectively. Structural characterisation along with analyses of solubility, residual water content and drug content of the inclusion complexes was performed. The intestinal microflora of male rats was used to study MAG degradation in vitro. At three concentrations, the degradation of both the inclusion complexes was slower than that of the MAG monomer, MAG and CD mixtures and the MAG-poloxamer 188 micelle. There were no statistically significant differences in the degradation of the MAG/ß-CD and MAG/HP-ß-CD inclusion complexes. A simulation first-order equation of the degradation parameters revealed that the degradation of the inclusion complexes was slower and pronounced, judging by slope. The experimental findings were verified by molecular docking for predicting the stable molecular structure of the inclusion complexes. In conclusion, the inclusion complexes partially protected MAG from degradation by the intestinal bacteria.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Bactérias/metabolismo , Compostos de Bifenilo/metabolismo , Intestinos/microbiologia , Lignanas/metabolismo , beta-Ciclodextrinas/química , Animais , Liofilização , Masculino , Simulação de Acoplamento Molecular , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Solubilidade
10.
Food Chem ; 298: 125004, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31260986

RESUMO

There is general interest in strategies to control polyphenol oxidase (PPO)-initiated enzymatic browning because it is often associated with declining food quality. Cyclodextrins are cyclic glucan oligosaccharides that form inclusion complexes with a number of PPO substrates. This study focuses on the effect of ß-cyclodextrins (ßCyD) on PPO-catalyzed reactions. Potato enzyme extracts and semi-purified potato PPO served as enzyme sources. Substrates included phenolics endogenous to potatoes. Reaction time-courses were followed spectrophotometrically; rates were compared by analysis of variance. Extents of ßCyD inhibition of PPO-catalyzed reactions are shown to be substrate specific and can be quantitatively accounted for based on degrees of ßCyD substrate sequestration. There was no evidence for direct irreversible ßCyD inactivation of potato PPO. An apparent "direct PPO inactivation" by ßCyD is shown to result from a sequence of sequestration-dependent reactions that occur in commonly employed assay systems for the quantification of PPO in fruits and vegetables.


Assuntos
Catecol Oxidase/química , Catecol Oxidase/metabolismo , Solanum tuberosum/enzimologia , beta-Ciclodextrinas/química , Catálise , Catecol Oxidase/antagonistas & inibidores , Fenóis/química , Fenóis/metabolismo , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Especificidade por Substrato , beta-Ciclodextrinas/metabolismo
11.
Cryo Letters ; 40(4): 219-225, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31278402

RESUMO

BACKGROUND: Rosmarinus officinalis essential oil (Rom) has been reported recently to be of interest for use in sperm cryopreservation. However, related to its lipophilic characteristics, encapsulation in cyclodextrin could enhance Rom positive effects by increasing its solubility in sperm extenders. OBJECTIVE: To compare the effect of Rom preloaded in hydroxypropyl-ß-cyclodextrin (Rom-cd) to Rom alone (Rom) on ram sperm conserved at 4°C. MATERIALS AND METHODS: Ram epididymal sperm was collected from six testes. Each collected sperm was split into four equal aliquots. The control aliquot was diluted with Tris extender (Tris + citric acid + fructose + penicillin), two aliquots were treated with Rom at 0.5µl ml-1 and 1µl ml-1 respectively, and one aliquot treated with Rom-cd at 1µl ml-1. All sperm aliquots were analyzed for motility after 0, 2, 4, 24 and 48 h of storage at 4°C using a Computer Aided Semen Analysis (CASA). Membrane integrity and oxidative stress status were measured after 48 h of storage. RESULTS: The results indicated that motility parameters were best preserved in the extender containing Rom-cd compared to the groups treated by Rom without cyclodextrin. Rom alone resulted to higher sperm motility than the control group. Lower oxidative stress and more cell membrane protection were observed in Rom treated samples, especially when using Rom-cd. CONCLUSION: The ability of Rom to protect ram sperm against cryopreservation damages was improved after encapsulation in hydroxypropyl-ß-cyclodextrin (HPßCD).


Assuntos
Óleos Voláteis/química , Rosmarinus/química , Preservação do Sêmen/veterinária , Motilidade Espermática , Espermatozoides/efeitos dos fármacos , beta-Ciclodextrinas/química , Animais , Membrana Celular , Criopreservação/veterinária , Masculino , Estresse Oxidativo , Ovinos , Espermatozoides/citologia
12.
Chem Commun (Camb) ; 55(65): 9697-9700, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31347623

RESUMO

An ultra-high sensitivity sensor with the function of chiral signal amplification has been proposed for the enantiomer discrimination of various amino acid enantiomers based on charge transfer (CT)-induced SERS spectroscopy. The introduced TiO2 in this sensor improves the CT behavior and discrimination efficiency distinctly and enantiomeric discrimination is realized even at low concentration.


Assuntos
Compostos de Anilina/química , Nanopartículas Metálicas/química , Compostos de Sulfidrila/química , Triptofano/análise , beta-Ciclodextrinas/química , Ligações de Hidrogênio , Fenilalanina/análise , Fenilalanina/química , Prata/química , Análise Espectral Raman/métodos , Estereoisomerismo , Titânio/química , Triptofano/química , Tirosina/análise , Tirosina/química
13.
Artigo em Inglês | MEDLINE | ID: mdl-31148522

RESUMO

The capacity to control quadruplex formation, especially in cancer cells, is captivating and entails a reasonable comprehension of the ligand-G-quadruplex binding. Herein, we report an iminopyrenyl-ß-cyclodextrin conjugate interacting with duplex and G-quadrulex DNAs. In addition, the host: guest association of the established G-quadruplex binder, berberine, with the ß-cyclodextrin derivative is studied employing 2-D ROESY. NMR, UV-visible, and fluorescence spectroscopic techniques are utilized to explore the ß-cyclodextrin conjugate's interaction with the quadruplexes. The Binding constants are accounted for the association of the ligands to each of the DNAs viz., calf thymus DNA (duplex), kit22, telo24, and myc22 (quadruplexes). The modulation of the iminopyrenyl-ß-cyclodextrin binding to the DNAs are observed when berberine is loaded in the host molecule. A vivid distinction between the interactions of the ligands with duplex and quadruplex structures is inferred. Berberine-loaded iminopyrenyl-ß-cyclodextrin shows a higher affinity for binding to kit22.


Assuntos
Berberina/química , DNA/química , Quadruplex G , beta-Ciclodextrinas/química , Sítios de Ligação , Corantes Fluorescentes/química , Ligantes , Espectrometria de Fluorescência , Termodinâmica
14.
Food Chem ; 297: 124994, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31253277

RESUMO

Improving the extraction efficiency and stability of red beet compounds has gained the attention of researchers due to their high nutritional and health benefits. In this study, ß-cyclodextrin (ß-CD) enhanced ultrasound assisted extraction was used for the extraction of red beet extract, and lyophilized extracts were characterized with FTIR and DSC analyses. The samples extracted with aqueous 5% ß-CD solutions revealed the highest content of betanin (2.243 ±â€¯0.04 mg) and total phenolic compounds (20.03 ±â€¯1.28 mg GAE/g DW), and the highest DPPH inhibition activity (59.87 ±â€¯4.94%). Additionally, complexation with ß-CD significantly enhanced the stability of betanin, phenolic compounds and antiradical activity in the stored beverage and gummy candy models at various pH and temperature conditions during 28 days. In conclusion, ß-CD-enhanced ultrasound assisted extraction is a suitable approach to extracting and stabilizing the red beet compounds for application in food, nutraceutical, and medical fields.


Assuntos
Beta vulgaris/química , Extratos Vegetais/química , Extração em Fase Sólida/métodos , Sonicação , beta-Ciclodextrinas/química , Antioxidantes/química , Beta vulgaris/metabolismo , Betacianinas/análise , Betacianinas/isolamento & purificação , Varredura Diferencial de Calorimetria , Armazenamento de Alimentos , Liofilização , Concentração de Íons de Hidrogênio , Fenóis/análise , Fenóis/isolamento & purificação , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura Ambiente
15.
Carbohydr Polym ; 219: 39-45, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31151539

RESUMO

An aqueous dispersion of alpha-lipoic acid (ALA) using octenylsuccinic anhydride-modified high-amylose starch (OS) was prepared, and thermal stability and cellular bioavailability of ALA were compared with those prepared using native high-amylose starch (HA) and beta-cyclodextrin (ß-CD). The ALA was homogeneously dispersed via the encapsulation of V-type amylose helices. In comparison with HA and ß-CD, OS exhibited a higher ALA absorption in Caco-2 cells, indicating the OS facilitated the intestinal epithelial transport of ALA. Oral administration of the encapsulated ALA in-vivo resulted in a higher maximum ALA plasma concentration and extended the terminal half-life by 30-40%. The area under the plasma concentration vs. time for the administration of ALA complexed by OS was 50% larger than that by HA, indicating the effectiveness of OS in enhancing the oral bioavailability of ALA. These results indicate that OS is an efficient carrier for ALA in oral delivery and bioavailability.


Assuntos
Amilose/química , Succinatos/química , Ácido Tióctico , Zea mays/química , beta-Ciclodextrinas/química , Administração Oral , Animais , Disponibilidade Biológica , Células CACO-2 , Meia-Vida , Humanos , Masculino , Ratos Sprague-Dawley , Ácido Tióctico/sangue , Ácido Tióctico/farmacocinética
16.
Anal Bioanal Chem ; 411(21): 5465-5479, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31177331

RESUMO

A benzylureido-ß-cyclodextrin was synthesized by the reaction of 6-amino-ß-cyclodextrin with an active benzyl isocyanate. Then, it was bonded to silica gel by a thiol-ene addition reaction, obtaining a new benzylureido-ß-cyclodextrin-based chiral stationary phase (BzCDP). Its chemical structure was characterized by infrared spectroscopy, elemental analysis, and solid-state nuclear magnetic resonance spectroscopy. The BzCDP was successfully used to separate phenylmercapturic acid (PMA) and benzylmercapturic acid (BMA) enantiomers, which were confirmed as biomarkers of exposure to benzene and toluene in human urine. The enantiomeric separations were also optimized through the investigation of related factors. The resolutions of PMA and BMA enantiomers could be up to 2.25 and 2.14, respectively, within 30 min under reversed-phase chromatography. Based on the optimal chromatographic and mass spectrometry conditions, a new LC-MS/MS quantitative method for the PMA and BMA enantiomers was established by negative ion multiple reaction monitoring (MRM) and an isotope-labeled PMA (d2-PMA) as an internal standard. The limits of detection (LODs) of enantiomers were less than 0.17 µg/L for PMA and 0.14 µg/L for BMA, and the averaged recoveries of enantiomers were in the range of 86~100% for PMA and 86~113% for BMA. The method had good reproducibility levels with the RSDs (3.5~11.3% for intra-day and 3.9~13.1% for inter-day). The method was successfully applied to urine testing of 60 painting and printing workers. The results showed that only L-PMA was detected in the urine of the Printers, while a high content of L-PMA (27.5~106 µg/L) and D-PMA (19.9~82.8 µg/L) can be detected simultaneously in the urine of the Painters, indicating that benzene pollution was more serious in this group. The positive rate of BMA was rather higher, indicating that toluene pollution was more common than benzene. BMA also existed in the form of two enantiomers (L-BMA and D-BMA), but the difference between the two types of occupational groups was small. It is a meaningful work to deeply study the existence and content of chiral markers in human urine, which will help to better understand and evaluate the harmful effects of benzene series on human beings. Graphical abstract.


Assuntos
Acetilcisteína/análogos & derivados , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , beta-Ciclodextrinas/química , Acetilcisteína/urina , Humanos , Limite de Detecção , Padrões de Referência , Reprodutibilidade dos Testes , Estereoisomerismo
17.
J Food Sci ; 84(6): 1592-1599, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31162880

RESUMO

The purpose of this study was to produce and characterize an inclusion complex between ß-cyclodextrin (ß-CD) and Exocarpium Citri Grandis essential oil (EEO), and to evaluate its antioxidant properties. The volatile compounds of EEO were characterized by gas chromatography-mass spectrometer. A comparison of the ß-CD, EEO, and the physical mixture with the inclusion complex revealed differences in their thermal stabilities and morphologies, which confirmed the formation of the ß-CD-EEO inclusion complex. Complexed with ß-CD, the ß-CD-EEO inclusion complex showed a higher stability and antioxidant activity when compared with physical mixture and EEO. Therefore, ß-CD can be used to form inclusion complexes with EEO to expand its potential applications in the food and drug industries. PRACTICAL APPLICATION: Exocarpium Citri Grandis is rich in essential oil and other ingredients. The optimized extraction, constituent composition, and encapsulation of EEO in ß-CD were investigated in this study. The results showed that the encapsulation process increased the antioxidant activity and stability of EEO, which provides both fundamental and practical knowledge for the application of EEO in the food and drug industries.


Assuntos
Antioxidantes/química , Citrus/química , Composição de Medicamentos/métodos , Óleos Voláteis/química , Estabilidade de Medicamentos , Frutas/química , beta-Ciclodextrinas/química
18.
Chem Commun (Camb) ; 55(50): 7203-7206, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31165120

RESUMO

Failure of autophagy induction results in the accumulation of abnormal mitochondria to cause neurodegenerative diseases. Artificial autophagy activation via the mitochondrial delivery of polyrotaxane with autophagy induced activity is achieved using a MITO-Porter, a nanodevice for mitochondrial delivery. This strategy can be applied to innovative research and therapy.


Assuntos
Autofagia/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Nanotecnologia/instrumentação , Rotaxanos/química , beta-Ciclodextrinas/farmacologia , Células HeLa , Humanos , Metilação , beta-Ciclodextrinas/química
19.
Food Chem ; 293: 550-560, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151647

RESUMO

Green coffee beans are rich in polyphenol chlorogenic acids (CGAs), which are decomposed to give caffeic acid (CFA) and quinic acid (QNA) upon roasting. CGA, CFA and QNA primarily confer the bitterness, astringency and acidity to the coffee brew. Aiming at the structural and thermodynamic insights into the ß-cyclodextrin (ß-CD) encapsulation of key compounds in coffee (CGA 1, CFA 2, and QNA 3), a systematic, comprehensive study using single-crystal X-ray diffraction and DFT calculation has been undertaken. Scrutinizing the X-ray-derived inclusion structures of 1-3 reveals that the CFA moiety plays a determinant role in complexation, in agreement with the DFT-derived relative thermodynamic stabilities. The guest molecules gain stability through OH⋯O hydrogen bonding with ß-CD and are well shielded in the ß-CD wall. The three stable ß-CD inclusion complexes with coffee key compounds suggest the implications of CDs as encapsulating agents for improving bioactivities and masking bitter taste in foods.


Assuntos
Antioxidantes/química , Ácidos Cafeicos/química , Ácido Clorogênico/química , Café/química , Ácido Quínico/química , Paladar/fisiologia , beta-Ciclodextrinas/química , Química Farmacêutica , Cristalografia por Raios X , Teoria da Densidade Funcional , Ligações de Hidrogênio , Termodinâmica
20.
Int J Nanomedicine ; 14: 4029-4044, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213813

RESUMO

Purpose: As well as functioning as a ligand that is selectively internalized by cells overexpressing human epidermal growth factor receptor-2 (HER2), HApt can exert cytotoxic effects by inducing cross-linking and subsequent translocation of HER2 to cytoplasmic vesicles, such downregulation of HER2 inhibits cell proliferation and induces apoptosis. We aimed to exploit the potential of HApt as both a targeting agent and antagonist to maximize the efficacy of mesoporous silica nanoparticle (MSN)-based drug release systems for HER2-positive breast cancer. Materials and methods: We fabricated novel HApt aptamer-functionalized pH-sensitive ß-cyclodextrin (ß-CD)-capped doxorubicin (DOX)-loaded mesoporous silica nanoparticles (termed MSN-BM/CD-HApt@DOX) for targeted delivery and selective targeting of HER2-positive cells. MSN-functionalized benzimidazole (MSN-BM) was used to load and achieve pH stimuli-responsive release of the chemotherapeutic agent doxorubicin (DOX). ß-cyclodextrin was introduced as a gatekeeper for encapsulated DOX and HApt as a selective HER2-targeting moiety and biotherapeutic agent. Results: Physical and chemical characterizations (FT-IR, XRD, TEM and BET) confirmed successful construction of MSN-BM/CD-HApt@DOX nanoparticles. In vitro release assays verified pH-sensitive DOX release. MSN-BM/CD-HApt@DOX (relative DOX concentration, 3.6 µg/mL) underwent HER2-mediated endocytosis and was more cytotoxic to HER2-positive SKBR3 cells than HER2-negative MCF7 cells. MSN-BM/CD-HApt@DOX also exhibited better uptake and stronger growth inhibition in SKBR3 cells than the control MSN-BM/CD-NCApt@DOX functionalized with a scrambled nucleotide sequence on CD. Overall, intracellular delivery of DOX and the biotherapeutic agent HApt resulted in synergistic cytotoxic effects in HER2-positive cancer cells in comparison to either DOX or HApt alone. Conclusion: MSN-BM/CD-HApt@DOX enables HER2-mediated targeting and biotherapeutic effects as well as pH-responsive DOX drug release, resulting in synergistic cytotoxic effects in HER2-overexpressing cells in vitro. This novel nanocarrier could potentially enable specific targeting to improve the efficacy of chemotherapy for HER2-positive cancer.


Assuntos
Neoplasias da Mama/patologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Receptor ErbB-2/metabolismo , Dióxido de Silício/química , Apoptose/efeitos dos fármacos , Benzimidazóis/química , Neoplasias da Mama/tratamento farmacológico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Liberação Controlada de Fármacos , Endocitose , Feminino , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas/ultraestrutura , Porosidade , Padrões de Referência , Espectroscopia de Infravermelho com Transformada de Fourier , beta-Ciclodextrinas/química
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