Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 381
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
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
2.
Life Sci ; 239: 116961, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31654745

RESUMO

Neuropathic pain (NP) is a difficult condition to treat because of the modest efficacy of available drugs. New treatments are required. In the study we aimed to investigate the effects of the essential oil from Lippia grata alone or complexed in ß-cyclodextrin (LG or LG-ßCD) on persistent inflammatory and neuropathic pain in a mouse model. We also investigated Ca2+ currents in rat dorsal root ganglion (DRG) neurons. Male Swiss mice were treated with LG or LG/ß-CD (24 mg/kg, i.g.) and their effect was evaluated using an acute inflammatory pleurisy model and nociception triggered by intraplantar injection of an agonist of the TRPs channels. We also tested their effect in chronic pain models: injection of Freund's Complete Adjuvant and partial sciatic nerve ligation (PSNL). In the pleurisy model, LG reduced the number of leukocytes and the levels of TNF-α and IL-1ß. It also inhibited cinnamaldehyde and menthol-induced nociceptive behavior. The pain threshold in mechanical and thermal hyperalgesia was increased and paw edema was decreased in models of inflammatory and neuropathic pain. PSNL increased inflammatory protein contents and LG and LG-ßCD restored the protein contents of TNF-α, NF-κB, and PKA, but not IL-1ß and IL-10. LG inhibited voltage gated Ca2+ channels from DRG neurons. Our results suggested that LG or LG-ßCD produce anti-hyperalgesic effect in chronic pain models through reductions in TNF-α levels and PKA, and inhibited voltage-gated calcium channels and may be innovative therapeutic agents for the management of NP.


Assuntos
Hiperalgesia/tratamento farmacológico , Lippia/metabolismo , beta-Ciclodextrinas/farmacologia , Animais , Dor Crônica/tratamento farmacológico , Modelos Animais de Doenças , Gânglios Espinais/efeitos dos fármacos , Hiperalgesia/metabolismo , Masculino , Camundongos , Neuralgia/tratamento farmacológico , Nociceptividade/efeitos dos fármacos , Óleos Voláteis/farmacologia , Dor/tratamento farmacológico , Dor/metabolismo , Medição da Dor/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , beta-Ciclodextrinas/metabolismo
3.
Biotechnol Lett ; 41(8-9): 921-928, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31286325

RESUMO

OBJECTIVES: To enhance the productivity of foreign protein in culture cells using baculovirus expression system. RESULTS: A low concentration of MßCD, with the optimal application concentration of 0.25 mM and the appropriate preincubation time range from 10 to 120 min, can efficiently enhance expression levels in both the AcMNPV and BmNPV expression systems. CONCLUSIONS: Preincubation with a low concentration MßCD enhance baculovirus infection and foreign protein expression productivity.


Assuntos
Expressão Gênica/efeitos dos fármacos , Proteínas Recombinantes/biossíntese , Ativação Transcricional/efeitos dos fármacos , beta-Ciclodextrinas/metabolismo , Vetores Genéticos
4.
Food Chem ; 298: 125004, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31260986

RESUMO

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


Assuntos
Catecol Oxidase/química , Catecol Oxidase/metabolismo , Solanum tuberosum/enzimologia , beta-Ciclodextrinas/química , Catálise , Catecol Oxidase/antagonistas & inibidores , Fenóis/química , Fenóis/metabolismo , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Especificidade por Substrato , beta-Ciclodextrinas/metabolismo
5.
Carbohydr Polym ; 218: 53-62, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31221343

RESUMO

In tuberculosis, macrophages serve as a host for Mycobacterium tuberculosis and hence targeting them with nanoparticles-based drug delivery could be the best strategy to achieve high therapeutic efficacy. Two tuberculosis drugs, namely rifampicin and levofloxacin, which have different mechanism of action on the bacteria, were complexed with cyclodextrin and conjugated to curdlan nanoparticles, to achieve simultaneous sustained release of both the drugs over a prolonged period of time. They are non-cytotoxic to both RAW 264.7 and L929 cells. They are taken up ˜1.8 times more by the macrophage cells through dectin-1 receptor than the fibroblast cells. They are also able to kill more than 95% of Mycobacterium smegmatis residing within the macrophages in 4 h. These results demonstrate that curdlan-CD nanoparticles can be a promising system for the loading and intracellular release of hydrophobic drugs into macrophages for various therapeutic applications.


Assuntos
Antituberculosos/farmacologia , Portadores de Fármacos/química , Macrófagos/microbiologia , Nanopartículas/química , beta-Ciclodextrinas/química , beta-Glucanas/química , Animais , Linhagem Celular , Portadores de Fármacos/metabolismo , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Levofloxacino/farmacologia , Macrófagos/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Mycobacterium smegmatis/efeitos dos fármacos , Nanopartículas/toxicidade , Rifampina/farmacologia , beta-Ciclodextrinas/metabolismo , beta-Ciclodextrinas/toxicidade , beta-Glucanas/metabolismo , beta-Glucanas/toxicidade
6.
Chemosphere ; 225: 135-138, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30870630

RESUMO

The increasing use of cyclodextrins (CDs) as host-molecules for host-guest complexes and their remediation application in environmental science requires to establish easily accessible models of "quantitative structure-activity relationships" (QSARs) to predict the binding constants. A new open-source molecular descriptor, so called spectrophores, was utilised to build 3D-QSAR models which have R2 of 0.95 and RMSE of 0.20.


Assuntos
Relação Quantitativa Estrutura-Atividade , beta-Ciclodextrinas/química , beta-Ciclodextrinas/metabolismo , Modelos Estatísticos
7.
Yakugaku Zasshi ; 139(2): 143-155, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30713223

RESUMO

Recently, the application of ß-cyclodextrins (ß-CDs) as therapeutic agents has received considerable attention. ß-CDs have been reported to have therapeutic effects on various diseases, such as Niemann-Pick type C (NPC) disease, a family of lysosomal storage disorders characterized by the lysosomal accumulation of cholesterol. To further improve the therapeutic efficacy of ß-CDs, the use of ß-CD-threaded polyrotaxanes (PRXs) has been proposed as a carrier of ß-CDs for NPC disease. PRXs are supramolecular polymers composed of many CDs threaded onto a linear polymer chain and capped with bulky stopper molecules. In this review, the design of PRXs and their therapeutic applications are described. To achieve the intracellular release of threaded ß-CDs from PRXs, stimuli-cleavable linkers are introduced in an axle polymer of PRXs. The stimuli-labile PRXs can dissociate into their constituent molecules by a cleavage reaction under specific stimuli, such as pH reduction in lysosomes. The release of the threaded ß-CDs from acid-labile PRXs in acidic lysosomes leads to the formation of an inclusion complex with the cholesterol that has accumulated in NPC disease patient-derived fibroblasts, thus promoting the extracellular excretion of the excess cholesterol. Moreover, the administration of PRXs to a mouse model of NPC disease caused significant suppression of the tissue accumulation of cholesterol, resulting in a prolonged life span in the model mice. Additionally, the induction of autophagy by the methylated ß-CD-threaded PRXs (Me-PRXs) is described. Accordingly, the stimuli-labile PRXs are expected to be effective carriers of CDs for therapeutic applications.


Assuntos
Ciclodextrinas , Portadores de Fármacos , Poloxâmero , Rotaxanos , beta-Ciclodextrinas/administração & dosagem , Animais , Autofagia/efeitos dos fármacos , Colesterol/metabolismo , Ciclodextrinas/química , Ciclodextrinas/metabolismo , Modelos Animais de Doenças , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Desenho de Drogas , Fibroblastos/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Lisossomos/metabolismo , Substâncias Macromoleculares , Metilação , Camundongos , Doenças de Niemann-Pick/tratamento farmacológico , Doenças de Niemann-Pick/metabolismo , Poloxâmero/química , Poloxâmero/metabolismo , Rotaxanos/química , Rotaxanos/metabolismo , beta-Ciclodextrinas/metabolismo , beta-Ciclodextrinas/farmacologia
8.
Bioconjug Chem ; 30(3): 583-591, 2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30678457

RESUMO

Nitric oxide (NO) exerts multiple functions in many life processes and was of great significance in a variety of biomedical scenarios. However, the mismatches between releasing locations and NO active sites seriously limited the available NO at areas of interest and greatly dampen the overall efficiency of delivery systems. Therefore, in the present study, a NO donor was developed to achieve intracellular delivery and release of NO to overcome the aforementioned challenges. Enhanced uptake and effective intracellular release of NO were realized via ß-cyclodextrin (ß-CD) mediated endocytosis and high level glutathione (GSH) inside cells, respectively. We demonstrated that intracellularly delivered NO would exert stronger bioeffects than premature release of NO outside targeted cells. Besides, ß-CD assisted cellular uptake proved indispensable in maximizing the influence of NO in modulating cellular behavior. These results demonstrated the significance of intracellular delivery and release of NO in improving its bioutilization. The carrier could efficiently inhibit proliferation of SMCs, while promoting the growth of ECs. Such cell-type-differed physiological effects were advantageous in re-endothelialization and might hold great potential in cardiovascular applications.


Assuntos
Preparações de Ação Retardada/metabolismo , Glutationa/metabolismo , Doadores de Óxido Nítrico/administração & dosagem , beta-Ciclodextrinas/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , GMP Cíclico/metabolismo , Endocitose , Humanos , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/farmacocinética , Doadores de Óxido Nítrico/farmacologia , Coelhos
9.
Bioorg Med Chem ; 27(5): 700-707, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30692022

RESUMO

In the field of nicotinic acetylcholine receptors (nAChRs), recognized as important therapeutic targets, much effort has been dedicated to the development of nicotinic analogues to agonize or antagonize distinct homo- and heteropentamers nAChR subtypes, selectively. In this work we developed di- and heptavalent nicotinic derivatives based on ethylene glycol (EG) and cyclodextrin cores, respectively. The compounds showed a concentration dependent inhibition of acetylcholine-induced currents on α7 nAChR expressed by Xenopus oocytes. Interesting features were observed with the divalent nicotinic derivatives, acting as antagonists with varied inhibitory concentrations (IC50) in function of the spacer arm length. The best divalent compounds showed a 16-fold lowered IC50 compared to the monovalent reference (12 vs 195 µM). Docking investigations provide guidelines to rationalize these experimental findings.


Assuntos
Antagonistas Nicotínicos/farmacologia , Polietilenoglicóis/farmacologia , Piridinas/farmacologia , Receptor Nicotínico de Acetilcolina alfa7/antagonistas & inibidores , beta-Ciclodextrinas/farmacologia , Animais , Feminino , Humanos , Ligantes , Lymnaea/química , Simulação de Acoplamento Molecular , Antagonistas Nicotínicos/síntese química , Antagonistas Nicotínicos/metabolismo , Oócitos/efeitos dos fármacos , Polietilenoglicóis/síntese química , Polietilenoglicóis/metabolismo , Ligação Proteica , Piridinas/síntese química , Piridinas/metabolismo , Xenopus laevis , Receptor Nicotínico de Acetilcolina alfa7/química , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , beta-Ciclodextrinas/síntese química , beta-Ciclodextrinas/metabolismo
10.
J Gen Virol ; 100(2): 156-165, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30484759

RESUMO

Classical swine fever virus (CSFV), the etiological agent of classical swine fever in pigs, is a member of the Pestivirus genus within the Flaviviridae family. It has been proposed that CSFV infection is significantly inhibited by methyl-ß-cyclodextrin (MßCD) treatment. However, the exact engagement of cellular cholesterol in the life cycle of CSFV remains unclear. Here, we demonstrated that pretreatment of PK-15 cells with MßCD significantly decreased the cellular cholesterol level and resulted in the inhibition of CSFV infection, while replenishment of exogenous cholesterol in MßCD-treated cells recovered the cellular cholesterol level and restored the viral infection. Moreover, we found that depletion of cholesterol acted on the early stage of CSFV infection and blocked its internalization into the host cells. Furthermore, we showed that 25-hydroxycholesterol, a regulator of cellular cholesterol biosynthesis, exhibited a potent anti-CSFV activity by reducing cellular cholesterol level. Taken together, our findings highlight the engagement of cholesterol in the life cycle of CSFV and its potential use as an antiviral target.


Assuntos
Colesterol/metabolismo , Vírus da Febre Suína Clássica/crescimento & desenvolvimento , Internalização do Vírus , Animais , Antivirais/farmacologia , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/virologia , Hidroxicolesteróis/farmacologia , Suínos , beta-Ciclodextrinas/metabolismo
11.
Anal Chem ; 90(22): 13607-13615, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30412380

RESUMO

ß-Cyclodextrin (ß-CD) is a nontoxic cyclic oligosachcharide that can encapsulate all or part of organic molecules of appropriate size and specific shape through noncovalent interaction. Herein, we report the influence of ß-CD complex formation of an antipyrine derivative on its metal ion sensing behavior. In aqueous solution, the antipyrine shows a turn-on fluorescence sensing of vanadyl ion, and in cyclodextrin medium it senses aluminum ion. The compound shows an unusual fluorescence quenching on binding with ß-cyclodextrin (log KSV = 2.34 ± 0.02). The differential metal ion sensing is due to the partial blocking of the chelating moiety by the cyclodextrin molecule. The structure of the antipyrine-cyclodextrin complex is optimized by two-dimensional rotating-frame Overhauser effect spectroscopy. The binding constant is determined by isothermal titration calorimetry (log K = 2.09 ± 0.004). The metal ion binding site is optimized by quanutm mechanical calculations. The lower limit of detection of vanadyl and aluminum ions, respectively, are 5 × 10-8 and 5 × 10-7 mol dm-3. This is the first report of selectivity of two different cations by a chemosensor in water and in ß-CD.


Assuntos
Antipirina/metabolismo , Metais/metabolismo , beta-Ciclodextrinas/metabolismo , Calorimetria/métodos , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral/métodos
12.
AAPS PharmSciTech ; 19(8): 3742-3750, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30255470

RESUMO

Curcumin chewing gums could be therapeutically beneficial if used by the head and neck cancer patients. High curcumin loading in chewing gums however is needed to achieve desired therapeutic effect. Preparing gums with high drug load is nonetheless challenging because of the negative impact of solids on their masticatory properties. The use of liquid flavors was found to partially solve this problem. The objectives of this study were to (1) determine the maximum amount of curcumin that can be loaded into co-compressed chewing gums made from Health in Gum® as the base and flavored with 1.5% peppermint oil, (2) determine if addition of sweeteners can improve the yield strength and compressibility of the gums when examined by a texture analyzer, (3) examine the effect of temperature over a storage period of one month on the physical stability of the chewing gums, and (4) study the impact of substituting curcumin with its inclusion complex with SBE-ß-CD on drug release. It was found that when flavored, Health in Gum® could load up to 25% curcumin by weight without compromising its masticatory properties. When tested for drug release, SBE-ß-CD was found to significantly increase the amount of curcumin dissolved within 30 min. Despite poor drug release from gums loaded with insoluble curcumin, the fragmentation of the gums during mastication by the Erweka tester is nonetheless expected to produce a suspension for absorption in the lower GIT. This study demonstrated how modulating gum composition and storage conditions can impact the mechanical properties of chewing gums with high solids content.


Assuntos
Química Farmacêutica/métodos , Goma de Mascar , Força Compressiva , Curcumina/síntese química , Excipientes/síntese química , beta-Ciclodextrinas/síntese química , Curcumina/metabolismo , Liberação Controlada de Fármacos , Excipientes/metabolismo , Solubilidade , Comprimidos , beta-Ciclodextrinas/metabolismo
13.
Carbohydr Polym ; 199: 649-660, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30143173

RESUMO

Two ß-cyclodextrin derivatives randomly appended on the primary face with both the nitric oxide (NO) photodonor 4-nitro-3-(trifluoromethyl)aniline and a mannose or α(1→2)mannobioside residue are reported to construct targeted NO photoreleasing nanocarriers. 2D ROESY and PGSE NMR suggested supramolecular homodimerization in water by inclusion of the nitroaniline group into the facing macrocycle cavities. Isothermal titration calorimetry on their concanavalin A lectin binding showed an exothermic binding event to the lectin and an endothermic process during the dilution of the conjugates. Both α(1→2)mannobioside and the nitroaniline moieties significantly enhanced the binding to the lectin. These effects might arise from a better fit within the carbohydrate-recognition site in the former case and a multivalent effect caused by homodimerization in the latter. Direct detection of NO by amperometric technique shows that both ß-cyclodextrin derivatives release this radical upon excitation with visible light with higher efficiency than the unfunctionalized NO photodonor.


Assuntos
Concanavalina A/metabolismo , Manosídeos/metabolismo , Doadores de Óxido Nítrico/metabolismo , beta-Ciclodextrinas/metabolismo , Luz , Substâncias Macromoleculares/síntese química , Substâncias Macromoleculares/química , Substâncias Macromoleculares/metabolismo , Substâncias Macromoleculares/efeitos da radiação , Manosídeos/síntese química , Manosídeos/química , Manosídeos/efeitos da radiação , Óxido Nítrico/análise , Doadores de Óxido Nítrico/síntese química , Doadores de Óxido Nítrico/química , Doadores de Óxido Nítrico/efeitos da radiação , Ligação Proteica , Termodinâmica , beta-Ciclodextrinas/síntese química , beta-Ciclodextrinas/química , beta-Ciclodextrinas/efeitos da radiação
14.
Sci China Life Sci ; 61(10): 1178-1188, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30159681

RESUMO

The rapid endothelialization of tissue-engineered blood vessels (TEBVs) can effectively prevent thrombosis and inhibit intimal hyperplasia. The traditional Chinese medicine ingredient icariin is highly promising for the treatment of cardiovascular diseases. ß-cyclodextrin sulfate is a type of hollow molecule that has good biocompatibility and anticoagulation properties and exhibits a sustained release of icariin. We studied whether icariin-loaded ß-cyclodextrin sulfate can promote the endothelialization of TEBVs. The experimental results showed that icariin could significantly promote the proliferation and migration of endothelial progenitor cells; at the same time, icariin could promote the migration of rat vascular endothelial cells (RAVECs). Subsequently, we used an electrostatic force to modify the surface of the TEBVs with icariin-loaded ß-cyclodextrin sulfate, and these vessels were implanted into the rat common carotid artery. After 3 months, micro-CT results showed that the TEBVs modified using icariin-loaded ß-cyclodextrin sulfate had a greater patency rate. Scanning electron microscopy (SEM) and CD31 immunofluorescence results showed a better degree of endothelialization. Taken together, icariin-loaded ß-cyclodextrin sulfate can achieve anticoagulation and rapid endothelialization of TEBVs to ensure their long-term patency.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Vasos Sanguíneos/efeitos dos fármacos , Células Progenitoras Endoteliais/efeitos dos fármacos , Flavonoides/farmacologia , beta-Ciclodextrinas/farmacologia , Animais , Prótese Vascular , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/fisiologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/fisiologia , Flavonoides/química , Ratos Sprague-Dawley , Sulfatos/metabolismo , Engenharia Tecidual/métodos , beta-Ciclodextrinas/química , beta-Ciclodextrinas/metabolismo
15.
AAPS PharmSciTech ; 19(6): 2710-2718, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29978292

RESUMO

Cyclodextrins are cyclic carbohydrates widely used as complexing and non-complexing excipients in drug delivery systems. The purpose of this work was to study the ability of hydroxypropyl-ß-cyclodextrin and ß-cyclodextrin to act as tablet fillers for direct compression. In this way, several parameters of the cyclodextrins were evaluated, namely: (i) the flow properties such as angle of repose, flow time, Carr index, and Hausner ratio; (ii) the compaction behavior, specifically the energies and forces exerted during tableting, the plasticity index, the lubrication efficiency, and compression profiles (force/time and work/displacement of the upper punch); and (iii) the influence on carbamazepine release characteristics from uncoated tablets, i.e., dissolution rate and disintegration time. In addition, these properties of the cyclodextrins were compared with those from other commonly used direct compression fillers (lactose monohydrate, mannitol, calcium hydrogen phosphate dihydrate, and microcrystalline cellulose) and co-processed excipients (microcrystalline cellulose/mannitol and lactose monohydrate/cellulose). Three main conclusions can be drawn: (i) the studied cyclodextrins can be used as tablet fillers for direct compression; (ii) hydroxypropyl-ß-cyclodextrin showed better properties than ß-cyclodextrin mainly at the level of the physics of compression (higher values of plasticity index and lubrication efficiency) and of the drug release characteristics (faster and greater dissolution rate and a shorter disintegration time); and (iii) lactose monohydrate and hydroxypropyl-ß-cyclodextrin displayed the best results. As there are people intolerant to lactose, hydroxypropyl-ß-cyclodextrin, although its cost is higher, can be considered a good substitute for lactose.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Química Farmacêutica/métodos , Força Compressiva , beta-Ciclodextrinas/química , 2-Hidroxipropil-beta-Ciclodextrina/metabolismo , Excipientes/química , Excipientes/metabolismo , Pressão , Sequestrantes/química , Sequestrantes/metabolismo , Solubilidade , Comprimidos , beta-Ciclodextrinas/metabolismo
16.
Spectrochim Acta A Mol Biomol Spectrosc ; 205: 497-502, 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30059876

RESUMO

In the present work we are reporting the synthesis and binding interaction of a saturated fatty acid containing 9-aminoacridine derivative (AC-PA) with ct-DNA and ß-cyclodextrin (ß-CD). From Steady-state fluorescence experiments this newly synthesized 9-aminoacridine derivative, AC-PA, shows more efficient binding interaction with ct-DNA as compared to the 9-aminoacridine (AC). The extent of interaction of AC-PA and AC with ct-DNA was found out by calculating the fluorescence quenching by using Stern-Volmer quenching equation. The calculated quenching constants of AC-PA and AC are (4.5 ±â€¯0.5) × 103M-1 (3.7 ±â€¯0.5) × 103M-1 respectively. The mechanism of fluorescence quenching of AC-PA and AC, were understand by using Stern-Volmer plots as well as time-resolved fluorescence experiments. The fluorescence quenching of AC-PA and AC by ct-DNA are static in nature and take place by formation of ground state complexes. The binding mode between AC-PA and AC were understood by DNA melting analysis experiment. The DNA melting analysis experiments were reveals that the binding interactions between fluorophores (AC-PA and AC) with ct-DNA are intercalative in nature. The melting temperature and mode of binding intercalative mode of binding between AC-PA and AC were further confirmed by DSC and CD experiments. The steady-state and time-resolved fluorescence parameters of AC-PA are quite sensitive towards the formation of inclusion complexes between AC-PA and ß-CD. Long hydrophobic tail containing acridine conjugate (AC-PA) shows more efficient binding interactions with the ß-CD and the calculated binding constants value of AC-PA is 0.51 × 102M-1. Whereas, the parent molecule, AC not showing any binding interactions with ß-CD.


Assuntos
Acridinas/química , DNA/química , beta-Ciclodextrinas/química , Acetilação , Acridinas/metabolismo , Sítios de Ligação , Varredura Diferencial de Calorimetria , Dicroísmo Circular , DNA/metabolismo , Espectrometria de Fluorescência , beta-Ciclodextrinas/metabolismo
17.
Water Res ; 142: 256-266, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29890474

RESUMO

As the main intermediate metabolite in anaerobic digestion of wasted activated sludge (WAS), volatile fatty acids (VFAs) are proper substrate for mixed culture (MC) polyhydroxyalkanoate (PHA) synthesis. To further optimize the performance of MC PHA production process, VFA_odd (i.e., VFA with odd carbon atoms) oriented acidification process was proposed and conducted in this study. Three regulation factors including reaction pH, fraction of added ß-cyclodextrin (ß-CD) and glycerol were selected and response surface methodology (RSM) was used to enhance and effectively regulate the VFA_odd production while maintaining enough acidification degree in the WAS acidification. High percentage of VFA_odd (larger than 60% and dominated by propionic acid) can be obtained in the operating condition area with glycerol addition ratio (quantified by C/N) ranging from 15 to 20 and reaction pH ranging from 8.0 to 9.5 when ß-CD addition was held at zero level (0.2 g/gTSS) according to the RSM. Semi-continuous acidification and MC PHA production assays further verified the reliability and effectiveness of the VFA_odd oriented acidification strategy. Microbial function group related to propionic acid production (Gprop) was defined based on the relationships between system function and microbial community structure, and 13 frequent species were found being involved in the Gprop. Roles of the group members in the oriented acidification were analyzed to understand the mechanisms of the regulation of VFA_odd production at microbial ecological level. A synergistic effect of WAS and glycerol on the VFA_odd production in the acidification process was revealed based on the ecological analysis.


Assuntos
Ácidos Graxos Voláteis/metabolismo , Microbiota/fisiologia , Poli-Hidroxialcanoatos/metabolismo , Esgotos/microbiologia , Gerenciamento de Resíduos/métodos , Reatores Biológicos/microbiologia , Carbono/química , Ácidos Graxos Voláteis/química , Glicerol/química , Glicerol/metabolismo , Concentração de Íons de Hidrogênio , Reprodutibilidade dos Testes , Esgotos/química , Gerenciamento de Resíduos/instrumentação , beta-Ciclodextrinas/química , beta-Ciclodextrinas/metabolismo
18.
AAPS PharmSciTech ; 19(6): 2658-2671, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29943282

RESUMO

Amisulpride (AMS) is an atypical antipsychotic agent used for the treatment of schizophrenia. The effect of different variables, i.e., the type of cyclodextrins (CDs), ratio of drug/CDs, and type of loading on the prepared AMS-CD liposomes (single and double loaded) was studied by applying 23 full factorial design. Double-loaded liposomes are loaded with AMS-hydroxyl propyl-ß-cyclodextrin (HP-ß-CD) in the aqueous phase and free drug in the lipophilic bilayer, while single-loaded liposomes are loaded only with AMS-HP-ß-CD in the aqueous phase. Entrapment efficiency, particle size, polydespersibility, and zeta potential were selected as dependent variables. Design Expert® software was used to obtain an optimized formulation with high entrapment efficiency (64.55 ± 1.27%), average particle size of 40.1 ± 2.77 nm, polydespersibility of 0.44 ± 0.37, and zeta potential of - 48.8 ± 0.28. Optimized formula was evaluated for in vitro release, surface morphology and stability study was also conducted. AMS-HP-ß-CD in double-loaded liposomes exhibited higher drug release than those in the conventional liposomes and in the single-loaded liposomes. The maximum plasma concentration (Cmax) of AMS in optimized AMS-HP-ß-CD double-loaded liposomal formulation increased by 1.55- and 1.29-fold, as compared to the commercial tablets and conventional liposomes, respectively. However, the relative bioavailability of AMS double-loaded liposomes was 1.94- and 1.28-folds of commercial tablet and conventional liposomes, respectively.


Assuntos
Antipsicóticos/química , Antipsicóticos/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Sulpirida/análogos & derivados , 2-Hidroxipropil-beta-Ciclodextrina/administração & dosagem , 2-Hidroxipropil-beta-Ciclodextrina/química , 2-Hidroxipropil-beta-Ciclodextrina/metabolismo , Amissulprida , Animais , Antipsicóticos/administração & dosagem , Disponibilidade Biológica , Portadores de Fármacos/administração & dosagem , Avaliação Pré-Clínica de Medicamentos/métodos , Liberação Controlada de Fármacos/fisiologia , Lipossomos , Masculino , Tamanho da Partícula , Ratos , Ratos Wistar , Sulpirida/administração & dosagem , Sulpirida/química , Sulpirida/metabolismo , Comprimidos , beta-Ciclodextrinas/química , beta-Ciclodextrinas/metabolismo
19.
AAPS PharmSciTech ; 19(5): 2255-2263, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29748896

RESUMO

Norfloxacin, an antibiotic that exists in different solid forms, has very unfavorable properties in terms of solubility and stability. Binary complexes of norfloxacin, in the solid form C, and ß-cyclodextrin were procured by the kneading method and physical mixture. Their effect on the solubility, the dissolution rate, and the chemical and physical stability of norfloxacin was evaluated. To perform stability studies, the solid samples were stored under accelerated storage conditions, for a period of 6 months. Physical stability was monitored through powder X-ray diffraction, high-resolution 13C solid-state nuclear magnetic resonance, and scanning electron microscopy. The results showed evidence that the kneaded complex increased and modulated the dissolution rate of norfloxacin C. Furthermore, it was demonstrated that the photochemical stability was increased in the complex, without affecting its physical stability. The results point to the conclusion that the new kneading complex of norfloxacin constitutes an alternative tool to formulate a potential oral drug delivery system with improve oral bioavailability.


Assuntos
Antibacterianos/química , Antibacterianos/metabolismo , Norfloxacino/química , Norfloxacino/metabolismo , beta-Ciclodextrinas/química , beta-Ciclodextrinas/metabolismo , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Varredura , Sequestrantes/química , Sequestrantes/metabolismo , Solubilidade , Difração de Raios X
20.
Chem Commun (Camb) ; 54(49): 6252-6255, 2018 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-29736504

RESUMO

Fluorescent unimolecular micelles (FUMs) with multicolor emission acting as fluorescent nanoagents for optical fluorescence imaging have, for the first time, been reported. The FUMs show good water-solubility, ultra-small size, and enhanced biocompatibility, which endow the FUMs with versatile applications including organelle labeling, multicolor markers and high tumor accumulation, revealing that our design can serve as a rational strategy for the development of UM-based fluorescent nanoagents for bioprocess monitoring.


Assuntos
Corantes Fluorescentes/metabolismo , Metacrilatos/metabolismo , Micelas , Neoplasias/diagnóstico por imagem , Polietilenoglicóis/metabolismo , beta-Ciclodextrinas/metabolismo , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Carbocianinas/síntese química , Carbocianinas/química , Carbocianinas/metabolismo , Linhagem Celular Tumoral , Citoesqueleto/metabolismo , Feminino , Fluoresceínas/síntese química , Fluoresceínas/química , Fluoresceínas/metabolismo , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Humanos , Lisossomos/metabolismo , Metacrilatos/síntese química , Metacrilatos/química , Camundongos Endogâmicos BALB C , Mitocôndrias/metabolismo , Tamanho da Partícula , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Rodaminas/síntese química , Rodaminas/química , Rodaminas/metabolismo , Solubilidade , beta-Ciclodextrinas/síntese química , beta-Ciclodextrinas/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA