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1.
J Nanobiotechnology ; 18(1): 13, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941501

RESUMO

BACKGROUND: During the past few decades, drug delivery system (DDS) has attracted many interests because it could enhance the therapeutic effects of drugs and reduce their side effects. The advent of nanotechnology has promoted the development of nanosized DDSs, which could promote drug cellular uptake as well as prolong the half-life in blood circulation. Novel polymer micelles formed by self-assembly of amphiphilic polymers in aqueous solution have emerged as meaningful nanosystems for controlled drug release due to the reversible destabilization of hydrophobic domains under different conditions. RESULTS: The amphiphilic polymers presented here were composed of cholesterol groups end capped and poly (poly (ethylene glycol) methyl ether methacrylate) (poly (OEGMA)) as tailed segments by the synthesis of cholesterol-based initiator, followed by atom transfer radical polymerization (ATRP) with OEGMA monomer. FT-IR and NMR confirmed the successfully synthesis of products including initiator and polymers as well as the Mw of the polymers were from 33,233 to 89,088 g/mol and their corresponding PDI were from 1.25 to 1.55 by GPC. The average diameter of assembled polymer micelles was in hundreds nanometers demonstrated by DLS, AFM and SEM. The behavior of the amphiphilic polymers as micelles was investigated using pyrene probing to explore their critical micelle concentration (CMC) ranging from 2.53 × 10-4 to 4.33 × 10-4 mg/ml, decided by the balance between cholesterol and poly (OEGMA). Besides, the CMC of amphiphilic polymers, the quercetin (QC) feeding ratio and polarity of solvents determined the QC loading ratio maximized reaching 29.2% certified by UV spectrum, together with the corresponding size and stability changes by DLS and Zeta potential, and thermodynamic changes by TGA and DSC. More significantly, cholesterol end-capped polymer micelles were used as nanosized systems for controlled drug release, not only alleviated the cytotoxicity of QC from 8.6 to 49.9% live cells and also achieved the QC release in control under different conditions, such as the presence of cyclodextrin (CD) and change of pH in aqueous solution. CONCLUSIONS: The results observed in this study offered a strong foundation for the design of favorable polymer micelles as nanosized systems for controlled drug release, and the molecular weight adjustable amphiphilic polymer micelles held potential for use as controlled drug release system in practical application.


Assuntos
Colesterol/química , Portadores de Fármacos/química , Nanopartículas/química , Polietilenoglicóis/química , Animais , Linhagem Celular , Sobrevivência Celular , Ciclodextrinas/química , Liberação Controlada de Fármacos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Micelas , Mioblastos/citologia , Mioblastos/efeitos dos fármacos , Pirenos/química , Quercetina/administração & dosagem , Quercetina/química
2.
Chemosphere ; 241: 125043, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31683417

RESUMO

Over the past few decades, cyclodextrin-based adsorbents have drawn worldwide attention as new-generation adsorbents for wastewater treatment due to its extraordinary physicochemical properties. This review outlined the recent development in the synthesis of cyclodextrin-based adsorbents as well as highlighted their applications in the removal of heavy metals, dyes, endocrine disrupting chemicals (EDCs), and mixed pollutants from water. The cross-linked and immobilized cyclodextrin-based adsorbents exhibited excellent adsorption performances. The removal of dyes and heavy metals were effectively controlled by ion exchanging, mainly depending upon the pH; while the adsorptions of EDCs always occurred in cyclodextrin cavities and pH-independent. An easier separation process between aqueous and adsorbents could be achieved compared to native cyclodextrin, which promoted the application of cyclodextrin-based adsorbents in practical industry. This review could provide an inspiration for the advanced study in the development of cyclodextrin-based adsorbents for high efficiency wastewater treatment.


Assuntos
Ciclodextrinas/química , Águas Residuárias/química , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Adsorção , Corantes/isolamento & purificação , Metais Pesados/isolamento & purificação
3.
J Chromatogr A ; 1609: 460654, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31679713

RESUMO

Cyclodestrins (CDs) are cyclic oligosaccharides well-known for their ability to form host-guest inclusion complexes with properly sized compounds. They have been used for decades as chiral selectors as well as drug delivery systems within the frameworks of separation science and pharmaceutical science. More recently, their use has been extended to the field of extractive science under the stimulus of additional advantageous characteristics, such as low-price, negligible environmental impact, non-toxicity, as arising from the fact that natural CDs are starch degradation products. To abate their solubility in water and generate novel sorbents for solid phase extraction, the following approaches have been employed: (i) immobilization onto inert materials (silica, attapulgite, etc.); (ii) immobilization onto nanomaterials (magnetic nanoparticles, titanium oxide, carbon nanotubes, graphene oxide, etc.); (iii) polymerisation with specific cross-linkers to form the so-called CD-based nanosponges. Particularly promising are these last ones for their selectivity, mesoporous structure, insolubility in aqueous media and good dispersibility. This review offers a concise overview on the state of art and future prospects of CDs in this important sector of the analytical chemistry, offering a critical perspective of the most significant applications.


Assuntos
Ciclodextrinas/química , Extração em Fase Sólida , Adsorção , Reagentes para Ligações Cruzadas/química , Grafite , Compostos de Magnésio/química , Nanoestruturas/química , Compostos de Silício/química
4.
Chemosphere ; 240: 124948, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31726616

RESUMO

Zearalenone is a xenoestrogenic mycotoxin produced by Fusarium species. High exposure with zearalenone induces reproductive disorders worldwide. Cyclodextrins are ring-shaped host molecules built up from glucose units. The apolar cavity of cyclodextrins can entrap so-called guest molecules. The formation of highly stable host-guest type complexes with cyclodextrins can decrease the biological effect of the guest molecule. Therefore, cyclodextrins may be suitable to decrease the toxicity of some xenobiotics even after the exposure. In this study, the protective effect of beta-cyclodextrins against zearalenone-induced toxicity was investigated in HeLa cells and zebrafish embryos. Fluorescence spectroscopic studies demonstrated the formation of stable complexes of zearalenone with sulfobutyl-, methyl-, and succinyl-methyl-substituted beta-cyclodextrins at pH 7.4 (K = 1.4-4.7 × 104 L/mol). These chemically modified cyclodextrins considerably decreased or even abolished the zearalenone-induced loss of cell viability in HeLa cells and mortality in zebrafish embryos. Furthermore, the sublethal effects of zearalenone were also significantly alleviated by the co-treatment with beta-cyclodextrins. To test the estrogenic effect of the mycotoxin, a transgenic bioindicator zebrafish model (Tg(vtg1:mCherry)) was also applied. Our results suggest that the zearalenone-induced vitellogenin production is partly suppressed by the hepatotoxicity of zearalenone in zebrafish. This study demonstrates that the formation of stable zearalenone-cyclodextrin complexes can strongly decrease or even abolish the zearalenone-induced toxicity, both in vitro and in vivo. Therefore, cyclodextrins appear as promising new mycotoxin binders.


Assuntos
Substâncias Protetoras/farmacologia , Zearalenona/toxicidade , Peixe-Zebra/embriologia , beta-Ciclodextrinas/farmacologia , Animais , Ciclodextrinas/química , Estrogênios/farmacologia , Células HeLa/efeitos dos fármacos , Humanos , Micotoxinas/metabolismo , Substâncias Protetoras/química , Reprodução/efeitos dos fármacos , beta-Ciclodextrinas/química , beta-Ciclodextrinas/metabolismo
5.
J Agric Food Chem ; 67(47): 13093-13107, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31693349

RESUMO

In this study, electrospinning of nanofibers from alpha-lipoic acid/cyclodextrin inclusion complex systems was successfully performed without having any polymeric matrix. Alpha-lipoic acid (α-LA) is a natural antioxidant compound which is widely used as a food supplement. However, it has limited water solubility and poor thermal and oxidative stability. Nevertheless, it is possible to enhance its water solubility and thermal stability by inclusion complexation with cyclodextrins. Here, hydroxypropyl-beta-cyclodextrin (HP-ß-CyD) and hydroxypropyl-gamma-cyclodextrin (HP-γ-CyD) were chosen as host molecules for forming inclusion complexation with α-LA. Accordingly, α-LA was inclusion complexed with HP-ß-CyD and HP-γ-CyD by using very high concentrated aqueous solutions of CyD (200%, w/v) having 1/1 and 2/1 molar ratio of α-LA/CyD. Except α-LA/HP-ß-CyD (1/1) solution, other α-LA/CyD solutions were turbid indicating the presence of some noncomplexed α-LA whereas α-LA/HP-ß-CyD (1/1) solution was very homogeneous signifying that α-LA was fully complexed with HP-ß-CyD. Even so, electrospinning was performed for all of the α-LA/HP-ß-CyD (1/1 and 2/1) and α-LA/HP-γ-CyD (1/1 and 2/1) aqueous solutions, and defect-free bead-less and uniform nanofibers were successfully obtained for all of the α-LA/CyD solutions. However, the electrospinning process for α-LA/CyD (1/1) systems was much more efficient than the α-LA/CyD (2/1) systems, and we were able to produce self-standing and flexible nanofibrous webs from α-LA/CyD (1/1) systems. α-LA was efficiently preserved during the electrospinning process of α-LA/CyD (1/1) systems and the resulting electrospun α-LA/HP-ß-CyD and α-LA/HP-γ-CyD nanofibers were produced with the molar ratios of ∼1/1 and ∼0.85/1 (α-LA/CyD), respectively. The better encapsulation efficiency of α-LA in α-LA/HP-ß-CyD nanofibers was due to higher solubility increase and higher binding strength between α-LA and HP-ß-CyD as revealed by the phase solubility test. α-LA was in the amorphous state in α-LA/CyD nanofibers and both α-LA/HP-ß-CyD and α-LA/HP-γ-CyD nanofibers were dissolved very quickly in water and also when they wetted with artificial saliva. Additionally, the antioxidant activity of pure α-LA and α-LA/CyD nanofibers was comparatively evaluated using ABTS radical cation assay. α-LA/CyD nanofibers have shown significantly higher antioxidant performance compared to pure α-LA owing to improved water solubility by CyD inclusion complexation. The thermal stability enhancement of α-LA in α-LA/CyD nanofibers was achieved compared to pure α-LA under heat treatment (100 °C for 24 h). These promising results support that antioxidant α-LA/CyD nanofibers may have potential applications as orally fast-dissolving food supplements.


Assuntos
Antioxidantes/química , Ciclodextrinas/química , Nanofibras/química , Ácido Tióctico/química , Portadores de Fármacos/química , Composição de Medicamentos , Estabilidade de Medicamentos , Cinética , Solubilidade
6.
Chem Commun (Camb) ; 55(97): 14558-14565, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31748764

RESUMO

The association of hydrophobic cavities with porphyrin derivatives has been used to mimic haemoprotein structures. The most employed cavity in this field is ß-cyclodextrin (ß-CD), and scaffolds combining ß-CDs and porphyrins are expected to inspire the combination of porphyrins and cucurbiturils in the near future. Aside from providing water solubility to various porphyrinic structures, the ß-CD framework can also modulate and control the reactivity of the metal core of the porphyrin. After a general introduction of the challenges faced in the field of haemoprotein models and the binding behavior of ß-CDs, this article will discuss covalent and non-covalent association of porphyrins with ß-CDs. In each approach, the role of the CD differs according to the relative position of the concave CD host, either directly controlling the binding and transformation of a substrate on the metalloporphyrin or playing a dual role of controlling the water solubility and selecting the axial ligand of the metal core. The discussion will be of interest to the cucurbituril community as well as to the cavitand community, as the information provided should be useful for the design of haemoprotein mimics using cucurbiturils.


Assuntos
Ciclodextrinas/química , Hemeproteínas/química , Modelos Moleculares , Porfirinas/química , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Estrutura Molecular , Solubilidade , Água/química
7.
Chem Commun (Camb) ; 55(100): 15037-15040, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31782430

RESUMO

We show that the selective enzymatic synthesis of specific cyclodextrins can be modulated using light. We use enzyme-mediated dynamic combinatorial chemistry to generate a mixture of interconverting linear and cyclic α-1,4-glucans, and employ an azobenzene photoswitch as a template. Using UV or blue light to switch between photostationary states with different azobenzene cis/trans isomeric ratios, we can promote the out-of-equilibrium assembly of either α-cyclodextrin or ß-cyclodextrin.


Assuntos
Ciclodextrinas/química , Glucosiltransferases/metabolismo , Luz , Compostos Azo/química , Biocatálise , Ciclodextrinas/metabolismo , Glucanos/química , Isomerismo , Termodinâmica , Raios Ultravioleta
8.
Curr Top Med Chem ; 19(25): 2357-2370, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31648636

RESUMO

Owing to their wide structural diversity and unique complexing properties, cyclodextrins (CDs) find manifold applications in drug discovery and development. The focus of this mini-review is on their uses as 'enabling excipients' both in the context of early drug discovery and in subsequent optimisation of drug performance. Features highlighted here include descriptions of the structures of CDs, synthetic derivatisation to fine-tune their properties, the nature of inclusion complexation of drugs within the CD cavity, methodology for the study of free and complexed hosts in the solid state and in solution, the inherent pharmacological activity of several CDs and its utility, novel CD-based drug delivery systems, and the role of CDs in drug discovery and optimisation. Illustrative examples are generally based on research reported during the last two decades. Application of CDs to the optimisation of the performance of established drugs is commonplace, but there are many opportunities for the intervention of CDs during the early stages of drug discovery, which could guide the selection of suitable candidates for development, thereby contributing to reducing the attrition rate of new molecular entities.


Assuntos
Ciclodextrinas/química , Animais , Química Farmacêutica , Sistemas de Liberação de Medicamentos , Descoberta de Drogas , Humanos , Estrutura Molecular
9.
Anal Chim Acta ; 1088: 137-143, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31623709

RESUMO

Here, we report a novel fluorescence method for the highly selective and sensitive detection of RNase H by combining the use of a dual-pyrene-labeled DNA/RNA duplex with supramolecular inclusion-enhanced fluorescence. Initially, the probe is in the "off" state due to the rigidness of the double-stranded duplex, which separates the two pyrene units. In the presence of RNase H, the RNA strand of the DNA/RNA duplex will be hydrolyzed, and the DNA strand transforms into a hairpin structure, bringing close the two pyrene units which in turn enter the hydrophobic cavity of a γ-cyclodextrin. As a result, the pyrene excimer emission is greatly enhanced, thereby realizing the detection of RNase H activity. Under optimal conditions, RNase H detection can be achieved in the range from 0.08 to 4 U/mL, with a detection limit of 0.02 U/mL.


Assuntos
Técnicas Biossensoriais/métodos , Ciclodextrinas/química , Limite de Detecção , Pirenos/química , Ribonuclease H/análise , Sequência de Bases , Linhagem Celular Tumoral , Sistema Livre de Células/enzimologia , Sondas de DNA/química , Sondas de DNA/genética , DNA de Cadeia Simples/química , DNA de Cadeia Simples/genética , Humanos , Modelos Moleculares , Conformação de Ácido Nucleico , Sondas RNA/química , Sondas RNA/genética , Ribonuclease H/sangue
10.
AAPS PharmSciTech ; 20(8): 314, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31529175

RESUMO

Baicalin is a flavone glycoside extracted from Scutellaria baicalensis, a traditional Chinese herbal medicine. Numerous pharmacological effects of baicalin were reported (e.g. antioxidant, anxiolytic); nevertheless, the most important physicochemical properties influencing the pharmacokinetic behaviour and the concomitant oral bioavailability have not yet been described in a comprehensive study. The aim of this project was to characterize the acid-base, lipophilicity, biorelevant solubility and permeability properties of the drug substance and providing scientific data to support the dosage form design. Another important objective was the comparative evaluation of six various baicalin-cyclodextrin (CD) inclusion complexes along with the creation of a suitable Drug Delivery System (DDS) for this BCS IV drug. Biorelevant profiling was carried out by NMR-pH titrations, saturation shake-flask and distribution coefficients (logP) measurements, while CD inclusion studies were fulfilled by experimental methods (phase solubility, 1H/13C NMR, 2D ROESY) and computational approaches. Due to low aqueous solubility (67.03 ± 1.60 µg/ml) and low permeability (Papp = 0.037 × 10-6 cm/s), baicalin is classified as BCS IV. The γ-CD complexation significantly increased the solubility of baicalin (~ 5 times). The most promoted chemical shift change occurred in baicalin-γ-CD complex. Computational studies showed disparate binding pattern for baicalin in case of ß- and γ-CD; furthermore, the calculated complexation energy was - 162.4 kJ mol-1 for ß-CD, while it was significantly stronger for γ-CD (- 181.5 kJ mol-1). The physicochemical and structural information of baicalin and its CD complexes introduced herein can create molecular basis for a promising DDS with enhanced bioavailability containing a bioactive phytopharmacon.


Assuntos
Antineoplásicos Fitogênicos/química , Ciclodextrinas/química , Flavonoides/química , Antineoplásicos Fitogênicos/administração & dosagem , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos , Flavonoides/administração & dosagem , Lipídeos/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Permeabilidade , Solubilidade , Termodinâmica
11.
J Agric Food Chem ; 67(40): 11066-11076, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31508948

RESUMO

The electrospinning of nanofibers (NFs) of cinnamaldehyde inclusion complexes (ICs) with two different hydroxypropylated cyclodextrins (CDs), hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and hydroxypropyl-γ-cyclodextrin (HP-γ-CD), was successfully performed in order to produce cinnamaldehyde/CD-IC NFs without using an additional polymer matrix. The inclusion complexation between cinnamaldehyde and hydroxypropylated CDs was studied by computational molecular modeling, and the results suggested that HP-ß-CD and HP-γ-CD can be inclusion complexed with cinnamaldehyde at 1:1 and 2:1 (cinnamaldehyde/CD) molar ratios. Additionally, molecular modeling and phase solubility studies showed that water solubility of cinnamaldehyde dramatically increases with cyclodextrin inclusion complex (CD-IC) formation. The HP-ß-CD has shown slightly stronger binding with cinnamaldehyde when compared to HP-γ-CD for cinnamaldehyde/CD-IC. Although cinnamaldehyde is a highly volatile compound, it was effectively preserved with high loading by the cinnamaldehyde/CD-IC NFs. It was also observed that cinnamaldehyde has shown much higher temperature stability in cinnamaldehyde/CD-IC NFs compared to uncomplexed cinnamaldehyde because of the inclusion complexation state of cinnamaldehyde within the hydroxypropylated CD cavity. Moreover, cinnamaldehyde still has kept its antibacterial activity in cinnamaldehyde/CD-IC NF samples when tested against Escherichia coli. In addition, cinnamaldehyde/CD-IC NF mats were fast-dissolving in water, even though pure cinnamaldehyde has a water-insoluble nature. In brief, self-standing nanofibrous mats of electrospun cinnamaldehyde/CD-IC NFs are potentially applicable in food, oral-care, healthcare, and pharmaceutics because of their fast-dissolving character, enhanced water solubility, stability at elevated temperature, and promising antibacterial activity.


Assuntos
Acroleína/análogos & derivados , Antibacterianos/química , Antibacterianos/farmacologia , Composição de Medicamentos/métodos , Acroleína/química , Acroleína/farmacologia , Ciclodextrinas/química , Composição de Medicamentos/instrumentação , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Nanofibras/química , Solubilidade , Temperatura Ambiente
12.
Chem Commun (Camb) ; 55(78): 11790-11793, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31524903

RESUMO

Balancing and neutralizing heparin dosing after surgeries and hemodialysis treatment is of great importance in medical and clinical fields. In this study, a series of new amphiphilic multi-charged cyclodextrins (AMCD)s as anti-heparin coagulants were designed and synthesized. The AMCD assembly was capable of selective heparin binding through multivalent bonding and showed a better neutralizing effect towards both unfractionated heparin and low molecular weight heparin than protamine in plasma. Meanwhile, an AMCD and vitamin K (VK) co-assembly was prepared to realize heparin-responsive VK release and provide a novel VK deficiency treatment for hemodialysis patients. This AMCD-VK co-assembly for heparin neutralization & vitamin K supplementation synergistic coagulation represents a promising candidate as a clinical anti-heparin coagulant.


Assuntos
Coagulantes/química , Ciclodextrinas/química , Vitamina K/química , Coagulantes/metabolismo , Ciclodextrinas/metabolismo , Heparina/química , Heparina/metabolismo , Tempo de Tromboplastina Parcial , Protaminas/química , Protaminas/metabolismo , Espectrofotometria , Vitamina K/metabolismo
13.
Carbohydr Polym ; 225: 115209, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521306

RESUMO

The very low aqueous solubility of celecoxib (CCB) hampers its ocular bioavailability. Thus, the aim of this study was to develop topical eye drop formulations containing cyclodextrin (CD) and a biocompatible polymer in an aqueous microsuspension. Aqueous CCB eye drop formulations containing biocompatible carbohydrate nano- and microparticles were prepared and their physicochemical and mucoadhesive properties evaluated. In vitro and ex-vivo permeation studies were performed as well as retinal cell viability tests. The appearance of the eye drop formulations and their pH, osmolality and viscosity were within acceptable range. The formulations containing hyaluronic acid (HA), a natural polysaccharide found in the eye, displayed excellent mucoadhesive properties. An increasing CCB content of the eye drops, obtained by heating method (sonication at the temperature of 70 °C for 1 h) to form ternary CCB/CD/polymer complex, resulted in higher drug permeation through a semipermeable membrane, simulated artificial vitreous humor and scleral tissues, especially from the formulation containing randomly methylated ßCD and HA (0.5% w/v). The CCB eye drops demonstrated no cytotoxicity in a human retina cell line.


Assuntos
Celecoxib , Sistemas de Liberação de Medicamentos/métodos , Soluções Oftálmicas/química , Disponibilidade Biológica , Celecoxib/química , Celecoxib/farmacocinética , Celecoxib/farmacologia , Linhagem Celular , Celulose/química , Celulose/farmacologia , Ciclodextrinas/química , Ciclodextrinas/farmacologia , Composição de Medicamentos , Humanos , Solubilidade , Viscosidade
14.
Mater Sci Eng C Mater Biol Appl ; 104: 109976, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499989

RESUMO

The preparation of fluorescent inorganic-organic polymer composites for biomedical applications has become one of the most interest research focuses recently. In this work, we reported a novel method for the preparation of Tb3+-doped luminescent layered double hydroxides (LDHs) based composites by taken advantage of a one-pot supramolecular chemistry. The adamantane can be immobilized on the surface of Tb3+-doped LDHs to obtain LDH-Ad, which could be further utilized for modified by the ß-cyclodextrin (ß-CD) containing hyperbranched polyglycerols (ß-CD-HPG) through the host-guest interaction. Based on the characterization results, we demonstrated that the hyperbranched polyglycerol could be facilely introduced on these fluorescent Tb3+-doped LDHs through the method described in this work. The obtained Tb3+-doped LDHs based polymer composites (LDHs-ß-CD-HPG) display improved water dispersibility and still maintain their fluorescence. The results based on various biological assays suggest that LDHs-ß-CD-HPG polymer composites are of low cytotoxicity and their cell uptake behavior can be effectively traced using confocal laser imaging. All of the above results demonstrated that the fluorescent Tb3+-doped LDHs based polymer composites could be effectively surface modified with hydrophilic hyperbranched polymers through a one-pot facile host-guest interaction and the resultant fluorescent composites are of excellent physicochemical properties and display great potential for biomedical applications. This novel surface modification method should also be important for fabrication of other multifunctional composites and therefore great advanced the development of biomedical applications of fluorescent LDHs based polymer composites and related materials.


Assuntos
Glicerol/química , Hidróxidos/química , Polímeros/química , Térbio/química , Celulose/química , Corantes/química , Ciclodextrinas/química , Fluorescência , Interações Hidrofóbicas e Hidrofílicas , Luminescência , Polimerização , Água/química , beta-Ciclodextrinas/química
15.
Carbohydr Polym ; 224: 115168, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472867

RESUMO

Kynurenic acid demonstrates antioxidant, neuroprotective and free radical scavenging properties. However, low aqueous solubility of kynurenic acid limits its therapeutic activity. In the present study, cyclodextrin nanosponges were used to improve the solubility and therapeutic activity of kynurenic acid. The formation of kynurenic acid loaded nanosponge was confirmed by different characterization techniques. The solubility of kynurenic acid was significantly increased with nanosponge (111.1 µg/ml) compared to free kynurenic acid (16.4 µg/ml) and ß-cyclodextrin (28.6 µg/ml). High drug loading (19.06%) and encapsulation efficiency (95.31%) were achieved with NS. The particle size and zeta potential of kynurenic acid loaded nanosponge was around 255.8 nm and -23 mV respectively. Moreover, higher solubilization of kynurenic acid loaded nanosponge produced better antioxidant activity compared to free kynurenic acid. The kynurenic acid loaded nanosponge and blank nanosponge were found nontoxic in the cytotoxicity assay. Thus, these studies demonstrated that nanosponges can be used as a carrier for the delivery of kynurenic acid.


Assuntos
Ciclodextrinas/química , Portadores de Fármacos/química , Depuradores de Radicais Livres/química , Ácido Cinurênico/química , Nanoestruturas/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/toxicidade , Depuradores de Radicais Livres/toxicidade , Humanos , Ácido Cinurênico/toxicidade , Solubilidade
16.
J Chromatogr A ; 1608: 460407, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31383356

RESUMO

A chiral methodology was developed for the first time to ensure the quality control of ivabradine, a novel anti-ischemic and heart rate lowering drug commercialized as a pure enantiomer. With this aim, electrokinetic chromatography (EKC) was employed and the enantiomeric separation of ivabradine was investigated using different anionic and neutral cyclodextrins (CDs) and amino acid-based chiral ionic liquids (CILs) as sole chiral selectors. Baseline separation was only achieved with sulfated CDs, and the best enantiomeric resolution was obtained with sulfated-γ-CD. Under the optimized conditions, ivabradine enantiomers were separated in 6 min with a resolution of 2.7. Nuclear magnetic resonance experiments showed a 1:1 stoichiometry for the enantiomer-CD complexes and apparent and averaged equilibrium constants were determined. The combined use of sulfated-γ-CD and different CILs as dual separation systems was investigated, resulting in a significant increase in the resolution. The use of 5 mM tetrabutylammonium-aspartic acid ([TBA][L-Asp]) in 50 mM formate buffer (pH 2.0) containing 4 mM sulfated-γ-CD were considered the best conditions in terms of resolution and migration times for ivabradine enantiomers. Nevertheless, as no inversion of the enantiomer migration order was observed when combining CILs and sulfated-γ-CD and a good enantiomeric resolution and efficiency were obtained using just sulfated-γ-CD as the sole chiral selector, the analytical characteristics of this method were evaluated, showing good recovery (98% and 103% for S- and R-ivabradine, respectively) and precision values (RSD < 5% for instrumental repeatability, < 6% for method repeatability and < 7% for intermediate precision). The limits of detection (LODs) were 0.22 and 0.28 µg mL-1 for S- and R-ivabradine, respectively, and the method enabled to detect a 0.1% of the enantiomeric impurity, allowing to accomplish the requirements of the International Conference on Harmonisation (ICH) guidelines. Finally, the method was applied to the analysis of a pharmaceutical formulation of ivabradine. The content of R-ivabradine was below the LOD and the amount of S-ivabradine was in agreement to the labeled content.


Assuntos
Aminoácidos/química , Química Farmacêutica/métodos , Cromatografia Capilar Eletrocinética Micelar , Ciclodextrinas/química , Líquidos Iônicos/química , Ivabradina/isolamento & purificação , Tampões (Química) , Ivabradina/química , Limite de Detecção , Estereoisomerismo , Sulfatos/química
17.
Macromol Rapid Commun ; 40(20): e1900323, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31429992

RESUMO

Reversible covalent bonds yield polymeric materials with functional characteristics such as self-healing, shape memory, stress relaxation, and stimuli-responsiveness. Here, photo-reversibly cappable polyrotaxanes are designed and the on-off controlled dissociation of their supramolecular architectures is demonstrated. The polyrotaxanes are synthesized by capping dithiobenzoates at both terminals of polyethylene glycol threaded through multiple α-cyclodextrins. Since dethreading of the α-cyclodextrins is prevented by the dithiobenzoate stoppers, the supramolecular dissociation is induced by their photo-cleavage. Subsequently, the cleaved dithiobenzoates spontaneously re-cap the polyrotaxane terminals in darkness. Thus, the supramolecular dissociation can be modulated by photo-reversible capping of the dithiobenzoate stoppers. These polyrotaxanes with dithiobenzoate stoppers are promising functional materials for photo-controlling physical properties and structures.


Assuntos
Ciclodextrinas/química , Luz , Poloxâmero/química , Rotaxanos/química , Benzoatos/química , Ciclodextrinas/síntese química , Poloxâmero/síntese química , Polietilenoglicóis/química , Rotaxanos/síntese química , alfa-Ciclodextrinas/química
18.
Int J Nanomedicine ; 14: 4589-4599, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31296988

RESUMO

Purpose: Ferulic acid (FA) is a poorly water-soluble natural antioxidant with anticancer activity. This poor solubility limits the application of FA in the food and pharmaceutical industry. Cyclodextrin nanosponges (CD-NSs) are a novel group of cross-linked CD derivatives which can be used to enhance the solubility of low-soluble bioactive compounds. Methods: In this study, FA was encapsulated into the NSs in the proportion of 1:4 (FA:NS). Diphenyl carbonate was used as a cross-linker in different proportions with ß-CD. Characterization of obtained NSs was performed using scanning electron microscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) analysis. Results: Our results revealed that the solubility of encapsulated FA was increased up to fifteenfold compared with pure FA in the proportion of 1:4 (CD:cross-linker). The results of FTIR, XRD, and DSC confirmed the interaction of FA with NSs. The cytotoxicity of encapsulated FA against MCF7 and 4T1 breast cancer cell lines was investigated using different concentrations of FA in 24, 48, and 72 hrs. The cytotoxicity assay indicated that FA treatment reduced viability and enhanced apoptosis of cancer cells. IC50 value of encapsulated FA (250 ppm) was decreased by threefold when compared with pure FA (750 ppm). Conclusion: In general, CD-NS was found to be a suitable delivery system for poorly soluble bioactives such as FA.


Assuntos
Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Ciclodextrinas/química , Nanoestruturas/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Varredura Diferencial de Calorimetria , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Feminino , Humanos , Microscopia Eletrônica de Varredura , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X
19.
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
/farmacologia , Anti-Infecciosos/farmacologia , Antioxidantes/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
20.
Molecules ; 24(13)2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31284697

RESUMO

Silica-supported metallic species have emerged as valuable green-chemistry catalysts because their high efficiency enables a wide range of applications, even at industrial scales. As a consequence, the preparation of these systems needs to be finely controlled in order to achieve the desired activity. The present work presents a detailed investigation of an ultrasound-promoted synthetic protocol for the grafting of ß-cyclodextrin (ß-CD) onto silica. Truly, ultrasound irradiation has emerged as a fast technique for promoting efficient derivatization of a silica surface with organic moieties at low temperature. Three different ß-CD silica-grafted derivatives have been obtained, and the ability of ß-CD to direct and bind Cu when CD is bonded to silica has been studied. A detailed characterization has been performed using TGA, phenolphthalein titration, FT-IR, diffuse reflectance (DR), DR UV-Vis, as well as the inductively-coupled plasma (ICP) of the ß-CD silica-grafted systems and the relative Cu-supported catalysts. Spectroscopic characterization monitored the different steps of the reaction, highlighting qualitative differences in the properties of amino-derivatized precursors and final products. In order to ensure that the Cu-ß-CD silica catalyst is efficient and robust, its applicability in Cu(II)-catalyzed alkyne azide reactions in the absence of a reducing agent has been explored. The presence of ß-CD and an amino spacer has been shown to be crucial for the reactivity of Cu(II), when supported.


Assuntos
Cobre/química , Ciclodextrinas/química , Ciclodextrinas/isolamento & purificação , Dióxido de Silício/química , Catálise , Estrutura Molecular , Dióxido de Silício/síntese química , Análise Espectral , Termogravimetria
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