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1.
Molecules ; 26(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34361579

RESUMO

Inclusion complexes between cyclodextrins (CDs) and active pharmaceutical ingredients (APIs) have potential for pharmaceutical formulation. Since crystallization of a given complex may result in the isolation of multiple crystal forms, it is essential to characterize these forms with respect to their structures and physicochemical properties to optimize pharmaceutical candidate selection. Here, we report the preparation and characterization of two crystallographically distinct hydrated forms of an inclusion complex between ß-cyclodextrin (ß-CD) and the antifungal API fluconazole (FLU) as well as temperature-concentration conditions required for their individual isolation. Determination of crystal water contents was achieved using thermoanalytical methods. X-ray analyses revealed distinct structural differences between the triclinic (TBCDFLU, space group P1) and monoclinic (MBCDFLU, space group C2) crystal forms. Removal of the crystals from their mother liquors led to rapid dehydration of the MBCDFLU crystal, while the TBCDFLU crystal was stable, a result that could be reconciled with the distinct packing arrangements in the respective crystals. This study highlights (a) the importance of identifying possible multiple forms of a cyclodextrin API complex and controlling the crystallization conditions, and (b) the need to characterize such crystal forms to determine the extent to which their physicochemical properties may differ.


Assuntos
Fluconazol/química , Modelos Moleculares , beta-Ciclodextrinas/química , Cristalografia por Raios X
2.
Molecules ; 26(12)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205446

RESUMO

A combination of Fourier transform infrared spectroscopy in attenuated total reflectance geometry (FTIR-ATR) and 2D correlation analysis (2D-COS) was applied here for the first time in order to investigate the temperature-dependent dynamical evolution occurring in a particular type of inclusion complex, based on sulfobutylether-ß-cyclodextrin (SBE-ß-CD) as hosting agent and Coumestrol (7,12-dihydorxcoumestane, Coum), a poorly-soluble active compound known for its anti-viral and anti-oxidant activity. For this purpose, synchronous and asynchronous 2D spectra were calculated in three different wavenumber regions (960-1320 cm-1, 1580-1760 cm-1 and 2780-3750 cm-1) and over a temperature range between 250 K and 340 K. The resolution enhancement provided by the 2D-COS offers the possibility to extract the sequential order of events tracked by specific functional groups of the system, and allows, at the same time, the overcoming of some of the limits associated with conventional 1D FTIR-ATR analysis. Acquired information could be used, in principle, for the definition of an optimized procedure capable to provide high-performance T-sensitive drug carrier systems for different applications.


Assuntos
Cumestrol/química , beta-Ciclodextrinas/química , Antioxidantes/química , Antivirais/química , Portadores de Fármacos/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Temperatura
3.
Molecules ; 26(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208150

RESUMO

Protocatechuic aldehyde (PCAL) and protocatechuic acid (PCAC) are catechol derivatives and have broad therapeutic effects associated with their antiradical activity. Their pharmacological and physicochemical properties have been improved via the cyclodextrin (CD) encapsulation. Because the characteristics of ß-CD inclusion complexes with PCAL (1) and PCAC (2) are still equivocal, we get to the bottom of the inclusion complexation by an integrated study of single-crystal X-ray diffraction and DFT full-geometry optimization. X-ray analysis unveiled that PCAL and PCAC are nearly totally shielded in the ß-CD wall. Their aromatic rings are vertically aligned in the ß-CD cavity such that the functional groups on the opposite side of the ring (3,4-di(OH) and 1-CHO/1-COOH groups) are placed nearby the O6-H and O2-H/O3-H rims, respectively. The preferred inclusion modes in 1 and 2 help to establish crystal contacts of OH⋅⋅⋅O H-bonds with the adjacent ß-CD OH groups and water molecules. By contrast, the DFT-optimized structures of both complexes in the gas phase are thermodynamically stable via the four newly formed host-guest OH⋯O H-bonds. The intermolecular OH⋅⋅⋅O H-bonds between PCAL/PCAC 3,4-di(OH) and ß-CD O6-H groups, and the shielding of OH groups in the ß-CD wall help to stabilize these antioxidants in the ß-CD cavity, as observed in our earlier studies. Moreover, PCAL and PCAC in distinct lattice environments are compared for insights into their structural flexibility.


Assuntos
Antioxidantes/química , Benzaldeídos/química , Catecóis/química , Hidroxibenzoatos/química , beta-Ciclodextrinas/química , Antioxidantes/administração & dosagem , Benzaldeídos/administração & dosagem , Catecóis/administração & dosagem , Cristalografia por Raios X , Sistemas de Liberação de Medicamentos/métodos , Ligação de Hidrogênio , Hidroxibenzoatos/administração & dosagem , Termodinâmica , beta-Ciclodextrinas/administração & dosagem
4.
Biosensors (Basel) ; 11(7)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209334

RESUMO

The excess of low-density lipoprotein (LDL) strongly promotes the accumulation of cholesterol on the arterial wall, which can easily lead to the atherosclerotic cardiovascular diseases (ACDs). It is a challenge on how to recognize and quantify the LDL with a simple and sensitive analytical technology. Herein, ß-cyclodextrins (ß-CDs), acting as molecular receptors, can bind with LDL to form stable inclusion complexes via the multiple interactions, including electrostatic, van der Waals forces, hydrogen bonding and hydrophobic interactions. With the combination of gold nanoparticles (Au NPs) and ß-CDs, we developed an electrochemical sensor providing an excellent molecular recognition and sensing performance towards LDL detection. The LDL dynamic adsorption behavior on the surface of the ß-CD-Au electrode was explored by electrochemical impedance spectroscopy (EIS), displaying that the electron-transfer resistance (Ret) values were proportional to the LDL (positively charged apolipoprotein B-100) concentrations. The ß-CD-Au modified sensor exhibited a high selectivity and sensitivity (978 kΩ·µM-1) toward LDL, especially in ultra-low concentrations compared with the common interferers HDL and HSA. Due to its excellent molecular recognition performance, ß-CD-Au can be used as a sensing material to monitor LDL in human blood for preventing ACDs in the future.


Assuntos
Técnicas Biossensoriais , Lipoproteínas LDL/análise , beta-Ciclodextrinas/química , Adsorção , Técnicas Eletroquímicas , Eletrodos , Ouro , Humanos , Nanopartículas Metálicas
5.
Molecules ; 26(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34279429

RESUMO

Racemic ketoprofen (KP) and ß-cyclodextrin (ß-CD) powder samples from co-precipitation (1), evaporation (2), and heating-under-reflux (3) were analysed using X-ray techniques and nuclear magnetic resonance (NMR) spectroscopy. On the basis of NMR studies carried out in an aqueous solution, it was found that in the samples obtained by methods 1 and 2, there were large excesses of ß-CD in relation to KP, 10 and 75 times, respectively, while the sample obtained by method 3 contained equimolar amounts of ß-CD and KP. NMR results indicated that KP/ß-CD inclusion complexes were formed and the estimated binding constants were approximately 2400 M-1, showing that KP is quite strongly associated with ß-CD. On the other hand, the X-ray single-crystal technique in the solid state revealed that the (S)-KP/ß-CD inclusion complex with a stoichiometry of 2:2 was obtained as a result of heating-under-reflux, for which the crystal and molecular structure were examined. Among the methods used for the preparation of the KP/ß-CD complex, only method 3 is suitable.


Assuntos
Cetoprofeno/química , Espectroscopia de Ressonância Magnética/métodos , Difração de Raios X/métodos , beta-Ciclodextrinas/química , Estrutura Molecular
6.
Int J Mol Sci ; 22(13)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34281189

RESUMO

Molecular modeling (MM) results for tedizolid and radezolid with heptakis-(2,3-diacetyl-6-sulfo)-ß-cyclodextrin (HDAS-ß-CD) are presented and compared with the results previously obtained for linezolid and sutezolid. The mechanism of interaction of chiral oxazolidinone ligands belonging to a new class of antibacterial agents, such as linezolid, tedizolid, radezolid, and sutezolid, with HDAS-ß-CD based on capillary electrokinetic chromatography (cEKC), nuclear magnetic resonance (NMR) spectroscopy, and MM methods was described. Principles of chiral separation of oxazolidinone analogues using charged single isomer derivatives of cyclodextrin by the cEKC method were presented, including the selection of the optimal chiral selector and separation conditions, complex stoichiometry, and binding constants, which provided a comprehensive basis for MM studies. In turn, NMR provided, where possible, direct information on the geometry of the inclusion complexes and also provided the necessary structural information to validate the MM calculations. Consequently, MM contributed to the understanding of the structure of diastereomeric complexes, the thermodynamics of complexation, and the visualization of their structures. The most probable mean geometries of the studied supramolecular complexes and their dynamics (geometry changes over time) were determined by molecular dynamics methods. Oxazolidinone ligands have been shown to complex mainly the inner part of cyclodextrin, while the external binding is less privileged, which is consistent with the conclusions of the NMR studies. Enthalpy values of binding of complexes were calculated using long-term molecular dynamics in explicit water as well as using molecular mechanics, the Poisson-Boltzmann or generalized Born, and surface area continuum solvation (MM/PBSA and MM/GBSA) methods. Computational methods predicted the effect of changes in pH and composition of the solution on the strength and complexation process, and it adapted the conditions selected as optimal during the cEKC study. By changing the dielectric constant in the MM/PBSA and MM/GBSA calculations, the effect of changing the solution to methanol/acetonitrile was investigated. A fairly successful attempt was made to predict the chiral separation of the oxazolidinones using the modified cyclodextrin by computational methods.


Assuntos
Oxazolidinonas/química , Tetrazóis/química , beta-Ciclodextrinas/química , Ciclodextrinas/química , Eletroforese Capilar/métodos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Modelos Moleculares , Oxazolidinonas/metabolismo , Estereoisomerismo , Tetrazóis/metabolismo
7.
ACS Appl Mater Interfaces ; 13(24): 27945-27954, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34110788

RESUMO

Magnetic resonance angiography (MRA) is an important imaging technique that can be used to identify and characterize various types of vascular diseases. However, currently used molecular contrast agents are unsuitable for MRA due to the short intravascular retention time, the whole-body distribution, and the relatively low contrast effect. In this study, we developed a vascular analysis contrast agent (i.e., VasCA) for MRA, which is a simple and biocompatible 1:1 host-guest assembly of PEGylated ß-cyclodextrin and gadolinium chelate with renal clearable size and high relaxivity (r1 = 9.27 mM-1 s-1). Its biocompatibility was confirmed by in vivo animal studies as well as in vitro 3D cell culture. In a tumor-bearing rat model, VasCA circulated in the blood vessels much longer (4.3-fold increase) than gadoterate meglumine (Dotarem) and was mainly excreted by the renal system after intravenous injection. This feature of VasCA allows characterization of tumor microvasculature (e.g., feeding and draining vessels) as well as visualization of small vessels in the brain and body organs. Furthermore, after treatment with an angiogenesis inhibitor (i.e., sorafenib), VasCA revealed the vessel normalization process and allowed the assessment of viable and necrotic tumor regions. Our study provides a useful tool for diverse MRA applications, including tumor characterization, early-stage evaluation of drug efficacy, and treatment planning, as well as diagnosis of cardiovascular diseases.


Assuntos
Meios de Contraste/química , Angiografia por Ressonância Magnética/métodos , Microvasos/diagnóstico por imagem , Animais , Quelantes/química , Gadolínio/química , Células HaCaT , Células Hep G2 , Humanos , Masculino , Polietilenoglicóis/química , Ratos Sprague-Dawley , beta-Ciclodextrinas/química
8.
ACS Appl Mater Interfaces ; 13(24): 28774-28781, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34114469

RESUMO

Three-dimensional (3D) scaffolds with chemical diversity are significant to direct cell adhesion onto targeted surfaces, which provides solutions to further control over cell fates and even tissue formation. However, the site-specific modification of specific biomolecules to realize selective cell adhesion has been a challenge with the current methods when building 3D scaffolds. Conventional methods of immersing as-prepared structures in solutions of biomolecules lead to nonselective adsorption; recent printing methods have to address the problem of switching multiple nozzles containing different biomolecules. The recently developed concept of macroscopic supramolecular assembly (MSA) based on the idea of "modular assembly" is promising to fabricate such 3D scaffolds with advantages of flexible design and combination of diverse modules with different surface chemistry. Herein we report an MSA method to fabricate 3D ordered structures with internal chemical diversity for site-selective cell adhesion. The 3D structure is prepared via 3D alignment of polydimethylsiloxane (PDMS) building blocks with magnetic pick-and-place operation and subsequent interfacial bindings between PDMS based on host/guest molecular recognition. The site-specific cell affinity is realized by distributing targeted building blocks that are modified with polylysine molecules of opposite chiralities: PDMS modified with films containing poly-l-lysine (PLL) show higher cell density than those with poly-d-lysine (PDL). This principle of selective cell adhesion directed simply by spatial distribution of chiral molecules has been proven effective for five different cell lines. This facile MSA strategy holds promise to build complex 3D microenvironment with on-demand chemical/biological diversities, which is meaningful to study cell/material interactions and even tissue formation.


Assuntos
Adesão Celular/efeitos dos fármacos , Dimetilpolisiloxanos/química , Polilisina/química , Animais , Linhagem Celular , Humanos , Ácido Hialurônico/química , Fenômenos Magnéticos , Camundongos , Polieletrólitos/química , Coelhos , Ratos , Estereoisomerismo , beta-Ciclodextrinas/química
9.
Int J Biol Macromol ; 182: 2048-2055, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34087295

RESUMO

Two-dimensional MoS2 is emerging as a unique platform for a wide range of biomedical applications including extracellular matrix mimics, drug delivery systems and antimicrobial agents. However, low processability and nonspecific interactions at biointerfaces are serious challenges that hamper the biomedical applications of this nanomaterial. Herein, we show how specific interactions between MoS2 and a gelatin matrix results in a biomimetic hydrogel with the self-healing and molecular recognition properties. ß-Cyclodextrin was conjugated to the surface of freshly exfoliated MoS2 through a one pot nucleophilic substitution reaction and the obtained cyclodextrin-functionalized MoS2 was used to construct an injectable, self-healable and flexible supramolecular hydrogel upon host-guest interactions with adamantane-modified gelatin matrix. Incorporation of almost 1 wt% of CDMoS2 into gelatin matrix with 1cm2 cross-section resulted in a hydrogel that was able to tolerate one hundred grams. Also, storage modulus (G'), loss modulus (G″) of the obtained hydrogel was 10 and 25 times higher than that for the neat gelatin, respectively. Due to its self-healing, molecular recognition and mechanical properties as well as its flexibility, injectability, and processability, MoS2gel is a promising candidate for a wide range of future biomedical applications including extracellular matrix mimics and tissue engineering.


Assuntos
Dissulfetos/química , Gelatina/química , Hidrogéis/química , Molibdênio/química , Animais , Reologia , Suínos , Difração de Raios X , beta-Ciclodextrinas/química
10.
Int J Biol Macromol ; 183: 1851-1860, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34087291

RESUMO

All kinds of soil conditioners have been used to improve soil quality. The application of many traditional soil conditioners was limited by single performance. In this study, a novel multifunctional microspheric soil conditioner was prepared based on Arabic gum, gelatin, chitosan and ß-cyclodextrin. Arabic gum and gelatin (AG-GL) microspheric carriers, which could load ferrous sulfate (FS), were synthesized via complex coagulation method. The AG-GL(FS) microspheres were covered by chitosan quaternary ammonium salt (CQAS) through single coagulation method. And ß-cyclodextrin (ß-CD) was used as the outermost shell to improve chemical stability of the soil conditioner by saturated solution method. Finally, the novel multifunctional microspheric soil conditioner AG-GL/CQAS/ß-CD-FS was obtained and characterized by Fourier transform infrared spectroscopy, thermogravimetric analyzer, polarizing microscope, scanning electron microscope and particle size analyzer. The novel soil conditioner shows good nutrient slowly-releasing, water retention, heavy metal ions adsorption and antibacterial performances with the particle size of 14-17 µm and high thermal decomposition temperature, which has the potential application in improving soil quality.


Assuntos
Quitosana/química , Gelatina/química , Goma Arábica/química , Solo/química , beta-Ciclodextrinas/química , Adsorção , Compostos Ferrosos/química , Microesferas , Tamanho da Partícula , Compostos de Amônio Quaternário/química , Sais , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
11.
Int J Biol Macromol ; 183: 2017-2029, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34097958

RESUMO

To enhance drug utilization and reduce their side effects, the strategy of "tumor-triggered targeting" was introduced to fabricate dual-pH-sensitive chitosan (CHI)/mesoporous silica nanoparticle (MSN)-based anticancer drug delivery system (DDS) in this work. Model drug doxorubicin hydrochloride (DOX) was loaded in MSN, which was modified with benzimidazole (Bz) group. Then chitosan-graft-ß-cyclodextrin (CHI-g-CD) was applied as the "gatekeeper" to cover MSN through host-guest interaction between ß-CD and Bz. After being coated with targeting peptide adamantane-glycine-arginine-glycine-aspartic acid-serine (Ad-GRGDS), methoxy poly(ethylene glycol) benzaldehyde (mPEG-CHO) was finally grafted on CHI through the pH-sensitive benzoic imine bond. Due to the dynamic protection of PEG, the obtained carriers were "stealthy" at pH 7.4, but could reveal the shielded targeting peptide and the positive charge of CHI in the weakly acidic environment achieved a "tumor-triggered targeting". Inside cancer cells, the interaction between ß-CD and Bz group could be destroyed due to the lower pH, resulted in DOX release. Both in vitro and in vivo studies proved the DDS could targeting induce cancer cell apoptosis, inhibit tumor growth, and reduce the cytotoxicity of DOX against normal cells. It is expected that the system named DOX@MSN-CHI-RGD-PEG could be a potential choice for cancer therapy.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Quitosana/química , Portadores de Fármacos , Nanopartículas , Silicatos/química , beta-Ciclodextrinas/química , Adamantano/química , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/metabolismo , Benzimidazóis/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Doxorrubicina/química , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Composição de Medicamentos , Feminino , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos BALB C , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Polietilenoglicóis/química , Porosidade , Carga Tumoral/efeitos dos fármacos
12.
Int J Biol Macromol ; 183: 2215-2226, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34097964

RESUMO

Triple negative breast cancer (TNBC) metastasis is still one of the obstacles in clinical treatment, while highly-effective cancer drugs usually cannot be used for their hydrophobicity and comprehensive system toxicity. This study built a kind of pH-sensitive nanoparticles (PP/H NPs) constructed by poly (lactic-co-glycolic acid) modified with ß-cyclodextrin (PLGA-ß-CD), polyethyleneimine grafted with benzimidazole (PEI-BM) and low molecular weight heparin (LMWH) to delivery Celastrol (Cela) and ferrocene (Fc) for breast cancer therapy. PLGA-ß-CD and PEI-BM were synthesized by amidation reaction, the amphipathic polymer nanoparticles with 108.37 ± 1.02 nm were self-assembled in water. After PP/H NPs treatment, the half maximal inhibitory concentration (IC50) decreased by 91% compared with Cela, and ROS level was also elevated. PP/H NPs led to substantial tumor inhibiting rate (TIR, 65.86%), utilized LMWH to strengthen the anti-metastasis effect of PP/H NPs. PP/H NPs took advantage of exogenous chemotherapeutics and endogenous ROS to inhibit tumor growth, and combined with LMWH to hinder breast cancer metastasis.


Assuntos
Antineoplásicos/farmacologia , Portadores de Fármacos , Compostos Ferrosos/farmacologia , Heparina de Baixo Peso Molecular/química , Metalocenos/farmacologia , Nanopartículas , Triterpenos Pentacíclicos/farmacologia , Polímeros Responsivos a Estímulos/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Antineoplásicos/química , Benzimidazóis/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Composição de Medicamentos , Feminino , Compostos Ferrosos/química , Concentração de Íons de Hidrogênio , Metalocenos/química , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Triterpenos Pentacíclicos/química , Polietilenoimina/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Espécies Reativas de Oxigênio/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Carga Tumoral/efeitos dos fármacos , beta-Ciclodextrinas/química
13.
J Chromatogr A ; 1651: 462298, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34111678

RESUMO

In this work, novel stationary phase coatings by zeolite SiO2NPs coupled with ß-cyclodextrin (ß-CD) or ß-CD/L-phenylalanine were developed for chiral open-tubular capillary electrochromatography (OT-CEC). The OT columns were prepared taking advantage of the strong adhesion of polydopamine in one-step method. Scanning electron micrography and electroosmotic flow were used to characterize the prepared single/dual-selector OT columns. Chiral separation of four chiral analytes (catechin/epicatechin, ephedrine/pseudoephedrine, ritodrine and salbutamol) was carried out in order to evaluate the performance of the prepared columns in OT-CEC with amperometric detection system. In terms of migration time, peak area, resolution, and selectivity factor of catechin/epicatechin and salbutamol, the run-to-run, day-to-day, and column-to-column repeatability were within 8.9%. Under the optimum conditions, the developed methods were applied for the analyses of Chinese herbal medicine Catechu herbs and salbutamol aerosol samples.


Assuntos
Eletrocromatografia Capilar/métodos , Nanopartículas/química , Dióxido de Silício/química , Zeolitas/química , Tampões (Química) , Concentração de Íons de Hidrogênio , Estereoisomerismo , beta-Ciclodextrinas/química
14.
J Chromatogr A ; 1651: 462338, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34153735

RESUMO

ß-Cyclodextrin can be functionalized by derivation of reactive hydroxyl on the ring due to its special chiral environment and structural characteristics, which can be used to identify or separate a variety of chiral substance. In this manuscript, a series of excellent chiral stationary phases for high-performance liquid chromatography were developed for enantioseparation by using anhydride modified ß-cyclodextrin bearing chiral (R/S)-α-phenethylamine or (S)-(+)-2-amino-1-propanol. They were characterized by elemental analysis, Fourier transform infrared spectra (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and BET. These chiral stationary phases presented good resolution and repeatability, about 17 kinds of enantiomers were effectively separated. And most of enantiomers were separated better than those reported in the literature in the same both normal and reversed phase modes. The RSD values of Rs for repeatability and column-to-column were below 0.44% and 2.83%, respectively. All results revealed that these new CSPs show great prospect for chiral separation in actual applications.


Assuntos
Anidridos/química , Cromatografia Líquida/métodos , beta-Ciclodextrinas/química , Cromatografia Líquida de Alta Pressão/métodos , Dióxido de Silício/química , Espectroscopia de Infravermelho com Transformada de Fourier , Estereoisomerismo
15.
Biomed Pharmacother ; 140: 111763, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34044273

RESUMO

Silibinin is effective in significantly inhibiting the growth of cancer cells which shown significant anti-neoplastic effects in a variety of in vitro and in vivo cancer models, including skin, breast, lung, colon, bladder, prostate and kidney carcinomas. So, development of a new method to its biomedical analysis in clinical samples in highly demanded. In this study, an innovative electroanalysis method for the accurate, sensitive and rapid recognition of silibinin in human plasma samples was proposed and validated. The sensing platform was designed using silver nanoparticles (AgNPs) dispersed on the polymeric layer of ß-cyclodextrin (ß-CD). AgNPs with cubic shape providing a large effective surface area for ß-CD electropolymerization. So, a layer with high electron conductivity boosting the detection electrochemical signals. Also, poly(ß-CD) providing an efficient substrate with cavities to interact with silibinin and its oxidation. Differential pulse voltammetry technique was conducted to measure silibinin concentration in human real samples. Under optimized conditions, proposed sensor indicated linear relationship between the anodic peak current and concentration of silibinin in the range of 0.0103-10.3 µM on the standard and human plasma samples. Based on obtained results, proposed sensor is an efficient platform to efficient therapy of cancer based on recognition of silibinin in clinical samples.


Assuntos
Antineoplásicos/sangue , Técnicas Biossensoriais , Nanopartículas Metálicas/química , Polímeros/química , Prata/química , Silibina/sangue , beta-Ciclodextrinas/química , Técnicas Eletroquímicas , Humanos , Silibina/química
16.
Food Chem ; 361: 130117, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34058659

RESUMO

To overcome the poor water solubility of curcumin, a curcumin-ß-cyclodextrin (Cur-ß-CD) complex was prepared as a novel photosensitizer. Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were used to verify the formation of Cur-ß-CD. Furthermore, the ROS generation capacity and photodynamic bactericidal effect were measured to confirm this Cur-ß-CD complex kept photodynamic activity of curcumin. The result showed Cur-ß-CD could effectively generate ROS upon blue-light irradiation. The plate count assay demonstrated Cur-ß-CD complex possess desirable photodynamic antibacterial effect against food-borne pathogens including Staphylococcus aureus, Listeria monocytogenes and Escherichia coli. The cell morphology determined by scanning electron microscope (SEM) and transmission electron microscope (TEM) showed Cur-ß-CD could cause cell deformation, surface collapse and cell structure damage of the bacteria, resulting in the leakage of cytoplasmic; while agarose gel electrophoresis and SDS-PAGE further illustrated the inactivation mechanisms by Cur-ß-CD involve bacterial DNA damage and protein degradation.


Assuntos
Antibacterianos/química , Curcumina/química , Fármacos Fotossensibilizantes/química , beta-Ciclodextrinas/química , Antibacterianos/farmacologia , Varredura Diferencial de Calorimetria , Curcumina/farmacologia , Escherichia coli/efeitos dos fármacos , Luz , Listeria monocytogenes/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Difração de Raios X , beta-Ciclodextrinas/farmacologia
17.
Molecules ; 26(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33947062

RESUMO

1-Pyrrolines are important intermediates of active natural products, such as the 2,5-dialkyl-1-pyrroline derivatives found in fire ant venoms. Here, 5-hexyl-2-methyl-3,4-dihydro-2H-pyrrole was synthesized by the enzymatic transamination/cyclization of 2,5-undecadione, and enantiodifferenciation was successfully achieved by capillary electrophoresis with sulfobutyl ether-ß-cyclodextrin as the chiral selector. The rationale of the enantiomeric discrimination was based on the results of a docking simulation that revealed the higher affinity of (S)-5-hexyl-2-methyl-3,4-dihydro-2H-pyrrole for the sulfobutyl ether-ß-cyclodextrin.


Assuntos
Pirróis/química , beta-Ciclodextrinas/química , Técnicas de Química Sintética , Ciclodextrinas/química , Eletroforese Capilar , Humanos , Modelos Moleculares , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Pirróis/análise , Pirróis/síntese química , beta-Ciclodextrinas/análise
18.
Int J Mol Sci ; 22(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946414

RESUMO

There is growing evidence that repurposed drugs demonstrate excellent efficacy against many cancers, while facilitating accelerated drug development process. In this study, bedaquiline (BDQ), an FDA approved anti-mycobacterial agent, was repurposed and an inhalable cyclodextrin complex formulation was developed to explore its anti-cancer activity in non-small cell lung cancer (NSCLC). A sulfobutyl ether derivative of ß-cyclodextrin (SBE-ß-CD) was selected based on phase solubility studies and molecular modeling to prepare an inclusion complex of BDQ and cyclodextrin. Aqueous solubility of BDQ was increased by 2.8 × 103-fold after complexation with SBE-ß-CD, as compared to its intrinsic solubility. Solid-state characterization studies confirmed the successful incorporation of BDQ in the SBE-ß-CD cavity. In vitro lung deposition study results demonstrated excellent inhalable properties (mass median aerodynamic diameter: 2.9 ± 0.6 µm (<5 µm) and fine particle fraction: 83.3 ± 3.8%) of BDQ-CD complex. Accelerated stability studies showed BDQ-CD complex to be stable up to 3 weeks. From cytotoxicity studies, a slight enhancement in the anti-cancer efficacy was observed with BDQ-cyclodextrin complex, compared to BDQ alone in H1299 cell line. The IC50 values for BDQ and BDQ-CD complex were found to be ~40 µM in case of H1299 cell line at 72 h, whereas BDQ/BDQ-CD were not found to be cytotoxic up to concentrations of 50 µM in A549 cell line. Taken together, BDQ-CD complex offers a promising inhalation strategy with efficient lung deposition and cytotoxicity for NSCLC treatment.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Diarilquinolinas/administração & dosagem , Portadores de Fármacos/química , Neoplasias Pulmonares/tratamento farmacológico , beta-Ciclodextrinas/química , Células A549 , Administração por Inalação , Antibióticos Antineoplásicos/farmacologia , Antituberculosos/administração & dosagem , Antituberculosos/farmacologia , Linhagem Celular Tumoral , Diarilquinolinas/farmacologia , Reposicionamento de Medicamentos , Humanos , Modelos Moleculares
19.
Anal Bioanal Chem ; 413(15): 3933-3944, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33903946

RESUMO

A novel ß-cyclodextrin derivative chemically bonded chiral stationary phase (EDACD) was synthesized by the reaction of mono-6-ethylenediamine-ß-cyclodextrin with the active alkyl isocyanate, anchoring to silica gel. After the successful analysis and characterization using scanning electron microscopy, Fourier transform infrared spectra, solid-state nuclear magnetic resonance spectra, elemental analysis, and thermogravimetric analysis techniques, the enantioselective performance of the as-prepared EDACD column was evaluated by non-steroidal antiinflammatory drugs and flavonoids under the reversed-phase HPLC condition. The factors that affected enantioseparation including mobile phase compositions and buffers were investigated in more detail. As a result, EDACD showed a satisfactory enantioselectivity for the tested drugs. With the mobile phase of acetonitrile and 20-mM ammonium formate adjusted to pH 4.0 using formic acid (85:15, v/v) at the flow rate of 0.6 mL min-1, the enantiomers of ibuprofen, carprofen, naproxen, indoprofen, ketoprofen, eriocitrin, naringin, and narirutin were separated with the best resolutions of 1.53, 1.64, 3.72, 2.40, 0.50, 0.61, 0.58, and 0.52. To adjust the proportion of acetonitrile to 80% (by volume), the enantiomers of pranoprofen and flurbiprofen were completely resolved with the best resolutions of 1.60 and 1.59. Additionally, by the study of the molecular docking, hydrogen bonding and inclusion complexation were believed to play an important role in chiral recognition. As a new material, EDACD will have a wider application in the analysis of chiral compounds.


Assuntos
beta-Ciclodextrinas/química , Cromatografia Líquida de Alta Pressão/métodos , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Análise Espectral/métodos , Estereoisomerismo
20.
Carbohydr Polym ; 262: 117868, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33838791

RESUMO

In this study, we have investigated the host-guest inclusion complexes between ß-cyclodextrin (ßCD), 2-hydroxypropyl-ß-cyclodextrin (2-HPßCD), and mono-6-tosyl-ß-cyclodextrin (TS-ßCD) excipients and two amino acids, such as L-arginine (L-Arg) and L-lysine (L-Lys). The formation of inclusion complexes was detected, and a comparative study was conducted at different pH, density, and viscosity. A physical mixture, comprising equal amount of amino acids was used to prepare the complex in a solid-state form. The experimental parameters, such as apparent molar volume, limiting apparent molar volume, partial molar volume were analyzed by measuring density at infinite dilution. The other quantities, such as dynamic viscosity, kinematic viscosity, relative viscosity, intrinsic viscosity, spatial viscosity, activation energy were determined for amino acid/ßCD complexes at various mass fractions of ßCDs and different temperatures. Finally, we found moderate (R2 > 0.5) and strong (R2 > 0.7) linear relationships (p-value < 0.0001) between the dynamic viscosity and the temperature: the temperature evaluation promotes the decrease in dynamic viscosity for amnio acid-ßCD (its derivatives) complexes. The results of this study emphasize important properties of analyzed complexes that can be utilized in the development of controlled drug delivery vectors.


Assuntos
Aminoácidos Básicos/química , beta-Ciclodextrinas/química , 2-Hidroxipropil-beta-Ciclodextrina/química , Arginina/química , Ciclodextrinas/química , Excipientes/química , Humanos , Lisina/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Temperatura , Viscosidade
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