Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 410
Filtrar
1.
Carbohydr Polym ; 227: 115287, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31590843

RESUMO

Lopinavir (LPV) is currently used in combination with ritonavir for the clinical management of HIV infections due to its limited oral bioavailability. Herein, we report the application of an in silico method to study cyclodextrin (CyD) host-guest molecular interaction with LPV for the rational selection of the best CyD for developing a CyD based LPV delivery system. The predicted CyD, a (2-hydroxy)propyl-gamma derivative with high degree of substitution (HP17-γ-CyD) was synthesized and comparatively evaluated with γ-CyD and the commercially available HP-γ-CyD. All complexes were prepared by supercritical assisted spray drying (SASD) and co-evaporation (CoEva) at molar ratios (1:1 and 1:2); and afterwards fully characterized. Results indicate a higher LPV amorphization and solubilization ability of HP17-γ-CyD. The SASD processing technology also enhanced LPV solubilization and release from complexes. The application of in silico methodologies is a feasible approach for the rational and/or deductive development of CyD drug delivery systems.


Assuntos
Antirretrovirais/química , Lopinavir/química , gama-Ciclodextrinas/química , Simulação por Computador , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Solubilidade
2.
Mater Sci Eng C Mater Biol Appl ; 106: 110281, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31753335

RESUMO

Artemisinin and its derivatives are currently recommended by World Health Organization for the treatment of malaria. Severe malaria requires a parenteral administration of artemisinin-based formulations. However, the effective use of artemisinin is limited by the pharmacokinetic characteristics of the drug (low water solubility, poor bioavailability and short half-life). To overcome some of these drawbacks, artemisinin-loaded surface-decorated nanoparticles were prepared by co-nanoprecipitation of γ-cyclodextrin bioesterified with C10 alkyl chains and polyethylene glycol (PEG) derivatives (polysorbate 80 and DMPE-mPEG2000). Using a single dose (1.5 mg kg-1 or 2 mg kg-1) by intravenous administration, we investigated the in vivo pharmacokinetic properties in healthy rats of two types of artemisinin-loaded nanoparticle formulations, namely, nanosphere and nanoreservoir systems versus an ethanolic-aqueous solution of artemisinin as reference. Significantly enhanced pharmacokinetic parameters were obtained with artemisinin-loaded nanoparticles. In comparison to reference formulation, the geometric mean exposures in plasma (AUC0-t) exhibited 2.35 and 3.26-fold increases when artemisinin was loaded in nanoreservoir and nanosphere systems, respectively. Its plasma half-life increased 4.00 and 6.25-fold and its clearance decreased up to 2.5 and 4.72-fold. Artemisinin was successfully administered intravenously by means of surface-decorated amphiphilic γ-cyclodextrin nanostructures and showed a longer elimination half-life with respect to an artemisinin solution in ethanol. Therefore, these systems are likely to provide significant advantages for the intravenous treatment of severe malaria.


Assuntos
Antimaláricos/farmacocinética , Artemisininas/química , Nanopartículas/química , gama-Ciclodextrinas/química , Administração Intravenosa , Animais , Antimaláricos/sangue , Antimaláricos/química , Artemisininas/sangue , Artemisininas/farmacocinética , Portadores de Fármacos/química , Meia-Vida , Masculino , Tamanho da Partícula , Polietilenoglicóis/química , Ratos , Ratos Wistar , Propriedades de Superfície
3.
Int J Mol Sci ; 20(19)2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31569423

RESUMO

Photodynamic therapy is an emerging treatment of tumor diseases. The complexes with γ-cyclodextrins (γ-CD) and fullerenes or their derivatives can be used as photosensitizers by direct injection into cancer cells. Using molecular mechanics and molecular dynamics methods, the stability and the geometry of the 2:1 complexes [(γ-CD)2/C70] are investigated analyzing the differences with the analogous C60 complexes, studied in a previous theoretical work and experimentally found to be much less efficient in cancer therapy. The inclusion complex of γ-CD and C70 has a 2:1 stoichiometry, the same as C60, but is significantly less stable and displays an unlike arrangement. In vacuo, mimicking an apolar solvent, the complex is compact, whereas in water the two γ-CDs encapsulate C70 forming a relatively stable complex by interacting through their primary rims, however exposing part of C70 to the solvent. Other higher-energy complexes with the γ-CDs facing different rims can form in water, but in all cases part of the hydrophobic C70 surface remains exposed to water. The stability and arrangement of these peculiar amphiphilic inclusion complexes having non-covalent interactions in water can be an important key for cancer therapy to enhance both the solubilization and the fullerene insertion into liposomes or cell membranes.


Assuntos
Fulerenos/química , Simulação de Dinâmica Molecular , Fármacos Fotossensibilizantes/química , gama-Ciclodextrinas/química , Conformação Molecular , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Análise Espectral , Relação Estrutura-Atividade , gama-Ciclodextrinas/farmacologia
4.
Drug Des Devel Ther ; 13: 2283-2293, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371922

RESUMO

Background: Trazodone (TRZ) is a second-generation non-tricyclic antidepressant derived from a triazolopyridine derivative, which is mainly used to treat emotional disorders and conditions related to depressive disorders. Purpose: This study investigated the design, development and characteristics of polyvinyl chloride (PVC) membrane sensors for trazodone HCl (TRZ). Methods: The developed sensing membranes were constructed using ß-cyclodextrin (ß-CD; sensor 1), γ-cyclodextrin (γ-CD; sensor 2) or 4-tert-butylcalix[8]arene (t-BC8; sensor 3) ionophores as sensing materials in addition to ionic sites and dioctyl phthalate in the PVC matrix. Results: Sensors 1, 2 and 3 displayed fast, stable and near-Nernstian response over a relatively wide trazodone concentration range (7.0×10-6-1×10-3, 5.0×10-5-1×10-3and 8.0×10-6-1.0×10-3 M, respectively), with detection limits of 2.2×10-6, 1.5×10-5 and 2.42×10-6 M, respectively in the pH range of 3.0-6.0. The sensors demonstrated good selectivity for TRZ in the presence of different ionic compounds. The accuracy and precision of the proposed sensors were assessed by the determination of 40.7 µg/ml of TRZ, which showed average recoveries of 99.6%, 99.1% and 98.5% with mean relative standard deviations of 2.4%, 2.5% and 2.6% for sensor 1, 2 and 3 respectively. Molecular modeling was used to calculate the host-guest binding energy. The lowest free binding energy was -6.243, -5.752 and -5.7105 kcal/mol for 1:1 stoichiometry host-guest complexes of trazodone and ß-CD, γ-CD and t-BC8, respectively, which was in-line with a Nernstian response. Conclusion: The investigated methods can be applied for the determination of TRZ in pharmaceutical preparations. The results of investigated dosage-form of TRZ show good agreement with those using the US Pharmacopeia method.


Assuntos
Técnicas Biossensoriais , Calixarenos/química , Ionóforos/química , Trazodona/análise , Trazodona/química , beta-Ciclodextrinas/química , gama-Ciclodextrinas/química , Estrutura Molecular
5.
Food Chem ; 294: 56-59, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31126500

RESUMO

Perilla oil is abundant in α-linolenic acid, which is metabolized to long-chain n-3 fatty acids. This study aimed to determine thermal stability and bioavailability of perilla oil that was powdered by inclusion complexation with γ-cyclodextrin. Fatty acid analysis revealed that the relative abundance of α-linolenic and linoleic acids in the complexes was not affected by heating at 40 °C for six days but decreased after heating at 60 °C for three days. No adverse events occurred in rats fed with an experimental diet containing the complexes for two weeks. Plasma α-linolenic and eicosapentaenoic acids in rats fed with diets containing complexes and liquid perilla oil were equally high, indicating the preserved bioavailability of perilla oil in the complexes. Plasma arachidonic acid decreased only in rats fed with a diet containing the complexes. Results suggest that the complexes have potential as a useful source of α-linolenic acid to increase plasma n-3 fatty acids.


Assuntos
Ácido alfa-Linoleico/química , gama-Ciclodextrinas/química , Animais , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Dieta , Ácidos Graxos/sangue , Cromatografia Gasosa-Espectrometria de Massas , Ácidos Linoleicos/sangue , Masculino , Óleos Vegetais/química , Óleos Vegetais/metabolismo , Ratos , Ratos Wistar , Espectrometria de Massas por Ionização por Electrospray , Temperatura , Ácido alfa-Linoleico/metabolismo , gama-Ciclodextrinas/metabolismo
6.
Carbohydr Polym ; 216: 224-230, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047061

RESUMO

γ-Cyclodextrin-based metal-organic framework (γCD-MOF) crystals were successfully synthesized using a vapor diffusion method. An applicability of γCD-MOF for encapsulation of immunosuppressive disease-modifying antirheumatic drug leflunomide (LEF) was examined. Loading of LEF in γCD-MOF was performed by impregnation and co-crystallization. The empty and loaded γCD-MOFs were characterized using X-ray powder diffraction, N2 adsorption/desorption, thermogravimetric analysis, 1H NMR and FTIR spectroscopy. It was shown that in the presence of γCD-MOF leflunomide is transformed into its pharmacologically active form - teriflunomide that can be also applied alone in the treatment of multiple sclerosis. It was demonstrated that teriflunomide released from γCD-MOF has improved pharmacologically relevant properties such as solubility, dissolution rate and membrane permeability. It can be proposed that γCD-MOF can be considered as novel strategy for delivery of leflunomide.


Assuntos
Antirreumáticos/química , Crotonatos/síntese química , Leflunomida/química , Estruturas Metalorgânicas/química , Pró-Fármacos/química , Toluidinas/síntese química , gama-Ciclodextrinas/química , Liberação Controlada de Fármacos , Cinética , Estruturas Metalorgânicas/síntese química , Oxirredução , Permeabilidade , Porosidade , Solubilidade , gama-Ciclodextrinas/síntese química
7.
Colloids Surf B Biointerfaces ; 180: 150-158, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31048240

RESUMO

The interaction of a cationic photosensitizer Safranin-O with liposome membranes having similar surface charge (negative) but differing in the presence of saturation on the lipid side-chain has been studied. To this end, dimyristoyl-l-R-phosphatidylglycerol (DMPG) and 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DOPG) phospholipids were employed to prepare small unilamellar vesicles. The dye is found to bind in the headgroup region of both the liposome membranes with significantly higher affinity to DOPG lipid containing unsaturated side chain. The effects of various cyclodextrins (CDs) on the stability of the probe-bound liposome membranes have also been investigated using steady-state and picosecond-resolved fluorescence as well as dynamic light scattering techniques. The modulations of the fluorescence properties of the lipid-bound dye were exploited to rationalize the membrane destabilization following interaction with the cyclodextrins. Experimental results reveal the selective interaction of DMPG membrane with CDs leading to rupture of the integrated structure of the liposome units accompanying release of the bound probe to the bulk aqueous phase. On the contrary, no discernible interaction of the CDs was observed with DOPG liposome membrane. Our results also show the differential extents of interaction of various CDs (α-CD, ß-CD, methyl-ß-CD, and γ-CD) with DMPG leading to varying degrees of release of the bound-dye molecule.


Assuntos
Fenazinas/química , Fármacos Fotossensibilizantes/química , alfa-Ciclodextrinas/química , beta-Ciclodextrinas/química , gama-Ciclodextrinas/química , Liberação Controlada de Fármacos , Cinética , Fosfatidilgliceróis/química , Soluções , Espectrometria de Fluorescência , Eletricidade Estática , Lipossomas Unilamelares/química
8.
Electrophoresis ; 40(15): 1913-1920, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30892703

RESUMO

The enantiomeric separation of 9-fluorenylmethoxycarbonyl chloride (FMOC)-homocysteine (Hcy) by CE was investigated using γ-CD and the chiral ionic liquid (R)-(1-hydroxybutan-2-yl)(trimethyl)azanium-bis(trifluoromethanesulfon)imidate (also called (R)-N,N,N-trimethyl-2-aminobutanol-bis(trifluoromethane-sulfon)imidate) (EtCholNTf2 ) as chiral selectors. Using 2 mM γ-CD and 5 mM EtCholNTf2 in 50 mM borate buffer (pH 9), FMOC-Hcy enantiomers were separated with a resolution value of 3.8. A reversal in the enantiomer migration order in comparison with the single use of γ-CD in the separation buffer was obtained. Then, NMR experiments were carried out to elucidate the interactions taking place in the enantiomeric separation of FMOC-Hcy. NMR analyses highlighted the formation of an inclusion complex since the hydrophobic group of FMOC-Hcy was inserted into the γ-CD cavity. Moreover, interactions between EtCholNTf2 and γ-CD were also observed, suggesting that the chiral ionic liquid would also enter the cavity of the γ-CD.


Assuntos
Eletroforese Capilar/métodos , Homocisteína/isolamento & purificação , Líquidos Iônicos/química , Espectroscopia de Ressonância Magnética/métodos , gama-Ciclodextrinas/química , Homocisteína/análise , Homocisteína/química , Imidazóis/química , Estereoisomerismo
9.
J Pharm Biomed Anal ; 169: 170-180, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30921691

RESUMO

NMR spectroscopy is used to investigate the host-guest complexation of (R)-tedizolid, such as tedizolid with the hydroxymethyl substituent at the C5 position of the oxazolidinone ring ((R)-TED) or tedizolid with 5-methyl dihydrogen phosphate ((R)-TED-PO4) with heptakis-(2,3-diacetyl-6-sulfo)-ß-cyclodextrin (HDAS-ß-CD), ß-CD and γ-CD, in particular to obtain information about the mode and strength of the guest complexation into the hydrophobic cavity of the host. The complex stoichiometries of 1:1 (host:guest) and 1:2 were detected in millimolar concentrations for HDAS-ß-CD and γ-CD with TED-PO4 complexes, respectively. In the meantime, the mixed of complexes with stoichiometries of 1:1 and 2:1 were found for ß-CD with both TED and TED-PO4, however the 1:1 complex had a significant advantage.The binding mode was proposed. The estimated binding constants Ka of the complexes of TED or TED-PO4 with CDs differ significantly in the order HDAS-ß-CD<<ß-CD<<γ-CD.


Assuntos
Oxazolidinonas/química , Tetrazóis/química , beta-Ciclodextrinas/química , gama-Ciclodextrinas/química , Espectroscopia de Ressonância Magnética/métodos , Estereoisomerismo
10.
Bioorg Med Chem ; 27(7): 1414-1420, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30808605

RESUMO

A cationic derivative of γ-cyclodextrin (GCD) modified with propylenediamine (PDA) was synthesized. It was shown that the derivative (GCD-PDA) is mucoadhesive and resistant to the digestion with ∝-amylase indicating that it may constitute an efficient oral delivery vehicle. GCD-PDA formed an inclusion complex with berberine (BBR), an alkaloid displaying a multitude of beneficial physiological effects. The complexed BBR penetrates a lipid membrane easier than the free one. Both uncomplexed BBR and that complexed with GCD-PDA was delivered to normal (NMuMG) and cancerous (4T1) murine mammary gland cells. In the normal cells both free and complexed BBR was homogeneously dispersed in the cytoplasm and was nontoxic up to 131 µM. In the cancerous cells uncomplexed BBR was also homogeneously dispersed but it was toxic to about 25% of cells at 131 µM, while the GCD-PDA/BBR complex was preferably localized in lysosomes and its toxicity doubled at this concentration compared to that of free BBR. Moreover, free BBR and GCD-PDA/BBR showed even more efficient inhibitory effect against murine melanoma (B16-F10) cells than against 4T1 cells.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos , gama-Ciclodextrinas/química , gama-Ciclodextrinas/farmacologia , Animais , Antineoplásicos/síntese química , Cátions/síntese química , Cátions/química , Cátions/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade , gama-Ciclodextrinas/síntese química
11.
Chem Commun (Camb) ; 55(21): 3156-3159, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30801096

RESUMO

Room temperature phosphorescent (RTP) γ-CD-CB[6]-cowheeled [4]rotaxanes were synthesized by implanting a naphthalene axle into the cavity of iodine-substituted γ-CDs. The strong green RTP was quenched exclusively by Trp while no RTP quenching was observed with other major physiological amino acids or with the Trp-containing protein HSA, demonstrating a highly specific sensing of free Trp.


Assuntos
Hidrocarbonetos Aromáticos com Pontes/química , Imidazóis/química , Substâncias Luminescentes/química , Rotaxanos/química , Triptofano/análise , gama-Ciclodextrinas/química , Hidrocarbonetos Aromáticos com Pontes/síntese química , Humanos , Imidazóis/síntese química , Substâncias Luminescentes/síntese química , Medições Luminescentes/métodos , Rotaxanos/síntese química , Temperatura , Triptofano/sangue , gama-Ciclodextrinas/síntese química
12.
Macromol Rapid Commun ; 40(3): e1800714, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30408258

RESUMO

A novel photoresponsive, water-soluble supramolecular dendronized polymer (SDP) is prepared through a γ -cyclodextrin (γ -CD)-coumarin host-guest interaction. The supramolecular formation, photoresponsive process, and fluorescence properties are investigated by nuclear magnetic resonance (NMR) techniques and spectrometric measurements. Upon different-wavelength light irradiation, this supramolecular polymer undergoes noncovalent polymer and covalent polymer conversion due to coumarin cycloaddition and cleavage reactions. In addition, SDP for bioimaging in Michigan Cancer Foundation-7 (MCF-7) cells is performed and results show that the obtained SDP has good biocompatibility and is lysosome-targetable. This research enriches the field of supramolecular dendrimers and the photo-stimulation response material may have application prospects in organelle-targeting applications.


Assuntos
Dendrímeros/química , Lisossomos/metabolismo , Polímeros/química , Água/química , Cumarínicos/química , Fluorescência , Humanos , Células MCF-7 , Espectroscopia de Ressonância Magnética , Microscopia Confocal , Modelos Químicos , Estrutura Molecular , Processos Fotoquímicos , Polímeros/síntese química , Solubilidade , gama-Ciclodextrinas/química
13.
Int J Pharm ; 556: 89-96, 2019 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-30528633

RESUMO

Assembled between γ-cyclodextrins (CD) and potassium ions, γ-cyclodextrin metal-organic frameworks (CD-MOF) create spatially extended and ordered cage-like structures. Herein, it was demonstrated that folic acid (FA), a model molecule, could be densely packed inside CD-MOF reaching 2:1 FA:CD molar ratio. This "Ship-in-a-Bottle" strategy leads to a 1450 fold increase of the apparent solubility of FA. Moreover, the bioavailability of FA inside CD-MOF in rats was enhanced by a factor of 1.48 as compared to free FA. The unique mechanism of FA incorporation in the CD-MOF 3D network was also explored, which was different from the conventional CD inclusion complexation. Taylor dispersion investigations indicated that FA was incorporated on the basis of a two-component model, which was further supported by a set of complementary methods, including SEM, XRPD, BET, SR-FTIR, SAXS and molecular simulation. The hypothesized mechanism suggested that: i) tiny FA nanoclusters formed inside the hydrophilic cavities and onto the surface of CD-MOF and ii) FA was included inside dual-CD units in CD-MOF. In a nutshell, this dual incorporation mechanism is an original approach to dramatically increase the drug apparent solubility and bioavailability, and could be a promising strategy for other poorly soluble drugs.


Assuntos
Ácido Fólico/administração & dosagem , Estruturas Metalorgânicas/química , Nanoestruturas , gama-Ciclodextrinas/química , Animais , Disponibilidade Biológica , Química Farmacêutica/métodos , Ácido Fólico/química , Ácido Fólico/farmacocinética , Interações Hidrofóbicas e Hidrofílicas , Masculino , Modelos Moleculares , Potássio/química , Ratos , Ratos Sprague-Dawley , Solubilidade
14.
J Sci Food Agric ; 99(2): 941-946, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30009400

RESUMO

Cyclodextrins (CDs) are macromolecules with several industrial applications, being particularly used in the food industry as health-promoting compounds protection agents, as flavour stabilizers, or to eliminate undesired tastes and browning reactions, among others. This study shows the effects of α- (10, 30 and 40 mmol L-1 ), ß- (3, 6 and 10 mmol L-1 ) and maltosyl-ß-CDs (30, 60 and 90 mmol L-1 ) use on the health-promoting glucoraphanin-sulforaphane system of a broccoli juice up to 24 h at 22 °C. Maltosyl-ß-CD (90 mmol L-1 ) highly retained glucoraphanin content after 24 h at 22 °C, showing better effectiveness than ß-CD (10 mmol L-1 ). Sulforaphane was efficiently encapsulated with ß-CD at just 3 mmol L-1 , and the sulforaphane formed was stable during 3 h at 22 °C. On the other hand, 40 mmol L-1 α-CD retained a high glucoraphanin content in broccoli juice. In contrast, glucoraphanin levels in juice without CDs decreased by 71% after 24 h. Consequently, CDs addition may potentially preserve glucoraphanin in this broccoli juice during industrial processing with the possibility to be later transformed by endogenous myrosinase after ingestion to the health-promoting sulforaphane. © 2018 Society of Chemical Industry.


Assuntos
Brassica/química , Aditivos Alimentares/química , Sucos de Frutas e Vegetais/análise , Glucosinolatos/química , Imidoésteres/química , Isotiocianatos/química , alfa-Ciclodextrinas/química , beta-Ciclodextrinas/química , gama-Ciclodextrinas/química , Reação de Maillard , Extratos Vegetais/química
15.
Chem Asian J ; 14(6): 847-852, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30506664

RESUMO

α-Amylase, an essential biomarker in pancreas related diseases and perform a major role in carbohydrates metabolism. Hence, monitoring the dynamic changes of α-amylase is crucial for better clinical diagnosis of diseases. However, the existing methods are suffered from low sensitivity, time consumption and indirect assay with aid of tool enzyme or inhibitor of competitive substrates, the rapid and non-destructive sensing of α-amylase in biological samples was highly desired. In this work, a very simple tetraphenylethylene motif and γ-cyclodextrin based supramolecular fluometric sensing system was firstly established. This system has no emission signal in aqueous media for the freely rotation of phenyl rings in the cavity of γ-cyclodextrin, but the AIE residues can be released in to water after the α-amylase hydrolysing γ-cyclodextrin, then turn on the fluorescence. In this system, the detection limit is calculated to be 0.007 U mL-1 in MES buffer with a linear range of 0-0.35 U mL-1 , having excellent selectivity to α-amylase compared to other proteins. At last, our probe can be applied to the quantitative analysis of α-amylase in human serum, showing potential in point of care testing.


Assuntos
Corantes Fluorescentes/química , Estilbenos/química , alfa-Amilases/metabolismo , gama-Ciclodextrinas/química , Bacillus/enzimologia , Corantes Fluorescentes/síntese química , Humanos , Limite de Detecção , Saliva/enzimologia , Espectrometria de Fluorescência , alfa-Amilases/análise , alfa-Amilases/sangue
16.
Molecules ; 23(12)2018 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-30567325

RESUMO

Amphotericin B is a low soluble broad-spectrum antifungal agent. Cyclodextrins can be added to amphotericin formulations to enhance both their solubility and antifungal properties. Semisolid amphotericin formulations containing gamma cyclodextrin (AGCD) were prepared and compared with two reference formulations-one of them without any solubility enhancer (A) and the other with DMSO (ADMSO). Rheological, the permeability through hairless mouse skin and antifungal characteristics of the different formulations were evaluated. All three semisolid formulations show low thixotropy characteristics. ADMSO was the formulation with the least consistency, lowest viscosity, and greatest extensibility. The AGCD formulation had the opposite behavior and had both the greatest consistency and viscosity and the lowest extensibility. The lowest permeability was obtained with the reference A formulation while both AGCD and ADMSO had a similar permeability enhancement. According to the antimicrobial in vitro efficacy trials, the AGCD formulation showed 45⁻60% more activity than the reference A formulation. It can be concluded that γ-cyclodextrin is a useful excipient to improve the solubility, permeability, and antifungal activity of amphotericin B in semisolid topical formulations.


Assuntos
Anfotericina B/química , Antifúngicos/química , Composição de Medicamentos/métodos , gama-Ciclodextrinas/química , Reologia
17.
Org Biomol Chem ; 16(38): 6870-6875, 2018 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-30229798

RESUMO

Photoexcitation of dibenzalacetones (1a-d) in homogeneous media and solid state yields a mixture of products with poor conversions. Irradiation of the reactants complexed to γ-cyclodextrin predominantly affords a single dimer (syn adduct 6) despite the possibility for several monomeric and dimeric products. High selectivity in the cavitand-mediated reaction along with the structural characterization of the inclusion complex provides insight into the supramolecular interactions that drive the self-assembly of the host-guest system.


Assuntos
Alcenos/química , gama-Ciclodextrinas/química , Alcenos/síntese química , Hidrocarbonetos Aromáticos com Pontes/síntese química , Hidrocarbonetos Aromáticos com Pontes/química , Chalconas/síntese química , Chalconas/química , Reação de Cicloadição , Dimerização , Imidazóis/síntese química , Imidazóis/química , Luz , Modelos Moleculares , Estereoisomerismo , gama-Ciclodextrinas/síntese química
18.
J Phys Chem Lett ; 9(19): 5718-5725, 2018 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-30226383

RESUMO

We use the electronic properties of 2D solid-state nanopore materials to propose a versatile and generally applicable biosensor technology by using a combination of molecular dynamics, nanoscale device simulations, and statistical signal processing algorithms. As a case study, we explore the classification of three epigenetic biomarkers, the methyl-CpG binding domain 1 (MBD-1), MeCP2, and γ-cyclodextrin, attached to double-stranded DNA to identify regions of hyper- or hypomethylations by utilizing a matched filter. We assess the sensing ability of the nanopore device to identify the biomarkers based on their characteristic electronic current signatures. Such a matched filter-based classifier enables real-time identification of the biomarkers that can be easily implemented on chip. This integration of a sensor with signal processing architectures could pave the way toward the development of a multipurpose technology for early disease detection.


Assuntos
Biomarcadores/metabolismo , Nanoporos , Algoritmos , Técnicas Biossensoriais , DNA/química , Condutividade Elétrica , Técnicas Eletroquímicas , Domínio de Ligação a CpG Metilada , Proteína 2 de Ligação a Metil-CpG/química , Proteína 2 de Ligação a Metil-CpG/metabolismo , Simulação de Dinâmica Molecular , Estrutura Terciária de Proteína , Semicondutores , gama-Ciclodextrinas/química
19.
Drug Des Devel Ther ; 12: 2529-2537, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30147300

RESUMO

Purpose: The formulation of topical ophthalmic products with appropriate therapeutic effect and patient compliance is a major challenge. To increase the efficiency of the ocular delivery of the drug, the enhancement of water solubility and the contact time of the drug on the surface of the cornea are necessary. In this work, prednisolone (PR)-containing eye drops were formulated with antimicrobial, mucoadhesive biopolymer and PR-cyclodextrin inclusion complex. This approach can be used for the development of innovative ophthalmic formulations. Materials and methods: After adjusting the optimal physiological parameters, the amount of the required cyclodextrin for the highest penetration of PR was determined by dialysis membrane diffusion study. The viscosity, surface tension and mucoadhesion of the eye drops were measured. The microbiological effectiveness of zinc-hyaluronate (ZnHA) was investigated by a standard method of the European Pharmacopoeia. Results: In this case, no significant difference of surface tension was measured in products with different amounts of cyclodextrin. According to the results of the tensile test, ZnHA as a mucoadhesive biopolymer improves the mucoadhesion of ophthalmic products. The antimicrobial stability of formulations preserved by ZnHA meets requirement B of the European Pharmacopoeia. Conclusion: It can be stated that the innovative PR-containing compositions are suitable for producing mucoadhesive, properly preserved aqueous ophthalmic solutions with increased bioavailability attributes.


Assuntos
Anti-Infecciosos/química , Portadores de Fármacos , Glucocorticoides/química , Ácido Hialurônico/química , Compostos Organometálicos/química , Prednisolona/química , gama-Ciclodextrinas/química , Adesividade , Administração Oftálmica , Anti-Infecciosos/administração & dosagem , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Composição de Medicamentos , Estabilidade de Medicamentos , Glucocorticoides/administração & dosagem , Ácido Hialurônico/administração & dosagem , Soluções Oftálmicas , Compostos Organometálicos/administração & dosagem , Prednisolona/administração & dosagem , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Solubilidade , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Tensão Superficial , Viscosidade
20.
J Chromatogr A ; 1568: 214-221, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30122164

RESUMO

The present study describes a rapid and effective capillary electrophoresis (CE) method for the enantioseparation of pindolol using single-isomer octa(6-O-sulfo)-γ-cyclodextrin. The complexation parameters were determined under neutral and high pH conditions to identify optimal separation conditions using a theoretical model. Baseline separation of pindolol enantiomers was achieved within 6 min in a sodium/MOPS buffer, pH 7.2, with a selector concentration of 6 mM. The method was validated according to the ICH guidelines using imidazole as an internal standard. Low limits of detection and quantification were found, specifically 1.2 µg/mL and 4 µg/mL (0.6 µg/mL and 2 µg/mL per enantiomer), respectively. The calibration curves showed good linearity, with a coefficient of determination R2 ≥ 0.999 over a 5 - 55 µg/mL concentration range and over a 50 - 300 µg/mL concentration range of the racemic mixture. The relative standard deviations (%RSD) of intra-day and inter-day precision were lower than 8% at LOQ level, lower than 3% at 50 µg/mL level and lower than 1.5% at 300 µg/mL level. Accuracy ranged from 95 to 103% (106% at LOQ level). The proposed method was successfully tested on a medical formulation of Visken® Sandoz intravenous solution and Visken® Teofarma pills for oral use.


Assuntos
Eletroforese Capilar/métodos , Pindolol/isolamento & purificação , Software , gama-Ciclodextrinas/química , Tampões (Química) , Calibragem , Concentração de Íons de Hidrogênio , Limite de Detecção , Reprodutibilidade dos Testes , Estereoisomerismo , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA