RESUMO
Abstract Oxazolidine derivatives (OxD) have been described as third-line antibiotics and antitumoral agents. The inclusion complexes based on cyclodextrin could improve the solubility and bioavailability of these compounds. A novel synthetic OxD was used, and its inclusion complexes were based on 2-hydroxy-beta-cyclodextrin (2-HPßCD). We conducted an in silico study to evaluate the interaction capacity between OxD and 2-HPßCD. Characterization studies were performed through scanning electron microscopy (SEM), Fourier-transformed infrared (FTIR), nuclear magnetic resonance spectroscopy (1H-NMR), X-ray diffraction (XRD), and thermal analyses. A kinetic study of the OxD was performed, including a cytotoxicity assay using peripheral blood mononuclear cells (PBMCs). The maximum increment of solubility was obtained at 70 mM OxD using 400 mM 2-HPßCD. SEM analyses and FTIR spectra indicated the formation of inclusion complexes. 1H-NMR presented chemical shifts that indicated 1:1 stoichiometry. Different thermal behaviors were obtained. The pharmacokinetic profile showed a short release time. Pure OxD and its inclusion complex did not exhibit cytotoxicity in PBMCs. In silico studies provided a foremost insight into the interactions between OxD and 2-HPßCD, including a higher solubility in water and an average releasing profile without toxicity in normal cells
Assuntos
Solubilidade/efeitos dos fármacos , Ciclodextrinas/agonistas , Microscopia Eletrônica de Varredura/métodos , Espectroscopia de Ressonância Magnética/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Espectroscopia de Prótons por Ressonância Magnética/métodos , Antibacterianos/análiseRESUMO
Genistein and its monoglucoside derivatives play important roles in food and pharmaceuticals fields, whereas their applications are limited by the low water solubility. Glycosylation is regarded as one of the effective approaches to improve water solubility. In this paper, the glycosylation of sophoricoside (genistein monoglucoside) was investigated using a cyclodextrin glucosyltransferase from Penibacillus macerans (PmCGTase). Saturation mutagenesis of D182 from PmCGTase was carried out. Compared with the wild-type (WT), the variant D182C showed a 13.42% higher conversion ratio. Moreover, the main products sophoricoside monoglucoside, sophoricoside diglucoside, and sophoricoside triglucoside of the variant D182C increased by 39.35%, 56.05% and 64.81% compared with that of the WT, respectively. Enzymatic characterization showed that the enzyme activities (cyclization, hydrolysis, disproportionation) of the variant D182C were higher than that of the WT, and the optimal pH and temperature of the variant D182C were 6 and 40℃, respectively. Kinetics analysis showed the variant D182C has a lower Km value and a higher kcat/Km value than that of the WT, indicating the variant D182C has enhanced affinity to substrate. Structure modeling and docking analysis demonstrated that the improved glycosylation efficiency of the variant D182C may be attributed to the increased interactions between residues and substrate.
Assuntos
Ciclodextrinas , Genisteína , Glucosiltransferases/metabolismo , Glicosilação , CinéticaRESUMO
The aim of the present study is to improve the solubility and antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin by formulating its inclusion complexes with 2-hydroxypropyl-ß-cyclodextrin in solution and in solid state. The phase solubility study was used to investigate the interactions between 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and 2-hydroxypropyl-ß-cyclodextrin and to estimate the molar ratio between them. The structural characterization of binary systems (prepared by physical mixing, kneading and solvent evaporation methods) was analysed using the FTIR-ATM spectroscopy. The antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and inclusion complexes prepared by solvent evaporation method was tested by the diffusion and dilution methods on various strains of microorganisms. The results of phase solubility studies showed that 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin formed the inclusion complexes with 2-hydroxypropyl-ß-cyclodextrin of AP type. The solubility of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin was increased 64.05-fold with 50% w/w of 2-hydroxypropyl-ß-cyclodextrin at 37 oC. The inclusion complexes in solid state, prepared by the solvent evaporation method, showed higher solubility in purified water and in phosphate buffer solutions in comparison with 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin alone. The inclusion complexes prepared by solvent evaporation method showed higher activity on Bacillus subtilis and Staphylococcus aureus compared to uncomplexed 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin due to improved aqueous solubility, thus increasing the amount of available 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin that crosses the bacterial membrane.
Assuntos
Solubilidade , Ciclodextrinas/agonistas , Anti-Infecciosos , Análise Espectral/instrumentação , Staphylococcus aureus/classificação , Bacillus subtilis/classificação , Espectroscopia de Infravermelho com Transformada de Fourier , DiluiçãoRESUMO
The freeze-drying technique, characterized by low-temperature processing, is especially suitable for sensitive volatile oils with thermal instability. However, there are few studies focusing on the retention of volatile oils in the processing of freeze-dried preparations. This study evaluated the effects of different addition methods(adsorption, emulsification, solid dispersion, and inclusion) on the retention rate of the main components in peppermint oil, aiming to explore the application feasibility of freeze-dried preparations of volatile oils. Firstly, the addition method was determined based on the retention rates of menthol in four freeze-dried preparations. Secondly, an orthogonal test was designed to optimize the preparation process based on the characteristics of the preferred addition method. The results showed that the most suitable preparation form of peppermint oil was inclusion with beta-cyclodextrin(β-CD), and the retention rate of menthol in freeze-drying was 86.36%. According to the two-step preparation process of inclusion and freeze-drying, we introduced the product of inclusion rate and retention rate, i.e., comprehensive retention rate, to determine the optimum processing parameters. The results showed that β-CD/oil ratio of 7∶1, inclusion temperature of 40 ℃, and inclusion time of 2 h were the optimum processing parameters. The product prepared with these parameter had the comprehensive retention rate of 68.41%, retention rate of 92.53%, and inclusion rate of 73.93%. The inclusion compound was white powder with significantly increased solubility. The pre-paration process based on cyclodextrin inclusion in this study is stable and reliable and provides a new idea for ensuring the efficacy and stability of volatile components in freeze-dried preparations.
Assuntos
Ciclodextrinas , Liofilização , Mentha piperita , Óleos Voláteis , Óleos de Plantas , Solubilidade , TecnologiaRESUMO
Lippia pedunculosa Hayek (EOLp) presenta efectos tripanocidas y amebicidas. En este trabajo se estudia su aceite esencial en modelos experimentales de analgesia e inflamación una vez que la prevalencia del dolor en la población genera un gran sufrimiento y discapacidad, y los medicamentos que se usan con mayor frecuencia tienen efectos secundarios indeseables. También se evalúa si la formulación del complejo de inclusión EOLp/ß-ciclodextrina (ß-CD) fue capaz de mejorar la actividad antinociceptiva de la EOLp sola. Los datos se evaluaron mediante análisis de varianza (ANOVA), seguido de la prueba de Tukey. Las diferencias se consideraron significativas si p<0,05. EOLp presentó un mejor efecto antinociceptivo en comparación con el complejo de inclusión EOLp/ß-CD. De esta manera, las ciclodextrinas parecen no ser eficientes para aceites esenciales con sustancias de peróxido. Sin embargo, en peritonitis, EOLp redujo la migración total de leucocitos y los niveles de IL-1ß en el líquido peritoneal, lo que confirma su efecto antiinflamatorio. Los efectos observados sugieren que EOLp es una buena y prometedora opción para el tratamiento de la inflamación y los trastornos relacionados con el dolor.
Lippia pedunculosa Hayek (EOLp) presents tripanocid and amebicid effects. However essential oil needs to be further studied in experimental models of analgesia and inflammation once the prevalence of pain in the population generates great suffering and disability and the drugs most often used have undesirable side effects. We also evaluated whether the inclusion complex formulation EOLp/ß-cyclodextrin (ß-CD) was able to improve the antinociceptive activity of the EOLp alone. Data were evaluated by analysis of variance (ANOVA), followed by Tukey's test. Differences were considered significant if p<0.05. EOLp presented better antinociceptive effect when compared to the EOLp/ß-CD inclusion complex. Thus, cyclodextrins appear not to be efficient for essential oils with peroxide substances. However, in peritonitis, EOLp reduced total leucocyte migration and IL-1ß levels in the peritoneal fluid, which confirmed its anti-inflammatory effect. The observed effects suggest that EOLp is the best promising option for the treatment of inflammation and pain-related disorders.
Assuntos
Animais , Masculino , Camundongos , Lippia/química , Analgésicos , Anti-Inflamatórios , Plantas Medicinais , Brasil , Ciclodextrinas , Medicina TradicionalRESUMO
Abstract The aim of this study was to assess the effect of a newly developed nanocomplex formed of hydroxypropyl-b-cyclodextrin and 1% titanium tetrafluoride (TiF4) after distinct complexation periods (12/72 h) on demineralization of bovine enamel in vitro. Enamel blocks (n=60) were allocated in different groups: Mili-Q water, hydroxypropyl-b-cyclodextrin, 1% TiF4, hydroxypropyl-b-cyclodextrin + 1% TiF4 after 12 h of complexation and hydroxypropyl-b-cyclodextrin + 1% TiF4 after 72 h of complexation. The samples were evaluated by surface microhardness, cross-sectional microhardness and micro-CT. Scanning electron microscopy and energy dispersive X-ray spectrometry (SEM/EDX) were also obtained. Hydroxypropyl-b-cyclodextrin + 1% TiF4 after 12 h complexation resulted in lower percentage of surface microhardness loss compared to Mili-Q water, hydroxypropyl-b-cyclodextrin, 1% TiF4 and hydroxypropyl-b-cyclodextrin + 1% TiF4 after 72 h of complexation group, with a large effect size (from 1.307 to 2.943) and high power (84.9 to 99%). All groups resulted in similar integrated mineral loss (ΔZ) obtained by both internal microhardness and micro-CT techniques. Enamel treated with TiF4 and TiF4 + hydroxypropyl-b-cyclodextrin groups showed a TiO2 glaze-layer, while EDX evaluation identified Ti. The solution containing the inclusion complex of hydroxypropyl-b-cyclodextrin + TiF4 with 12 h of complexation period demonstrated a significant ability to reduce surface demineralization of sound enamel under an artificial cariogenic challenge.
Resumo O objetivo deste estudo foi avaliar o efeito da 1-etil-3- (3-dimetilaminopropil) carbodiimida (EDC) na resistência de união de pinos de fibra de vidro em canais radiculares obturados com diferentes cimentos endodônticos. Setenta e oito pré-molares inferiores foram obturados com três cimentos endodônticos (n=26): Endofill (END), AH Plus (AHP) e Endosequence BC Sealer (EBS). Após o preparo do espaço para pino, dois subgrupos formaram-se conforme a cimentação dos pinos (n=13): com EDC e sem EDC (controle - CON). Os espécimes foram submetidos ao teste pull-out, classificação do modo de falha e avaliação da superfície do canal radicular por microscopia eletrônica de varredura após o deslocamento. Quanto à força de resistência de união, uma diferença estatisticamente significativa ocorreu entre os subgrupos EDC e CON apenas no END (p=0,001). Não foi detectada diferença entre os subgrupos CON (p=0,339). Contudo, no subgrupo EDC, o AHP apresentou maiores valores (END versus AHP: p=0,001; AHP versus EBS: p=0,016). Acerca da classificação dos modos de falha, o escore 1 (≥50% de cimento) foi o mais comumente observado, exceto para END + EDC. Restos de cimentos endodônticos e cimentos resinosos foram encontrados no terço cervical, mas sem diferença estatística (p=0,269), enquanto no terço médio, houve diferença (p=0,004). Em conclusão, o EDC diminui a resistência de união quando associado ao cimento END, sem alterar o modo de falha entre o cimento resinoso e o pino de fibra de vidro. O melhor desempenho foi observado quanto o EDC foi usado com o cimento AHP.
Assuntos
Animais , Ciclodextrinas , Fluoretos , Titânio , Bovinos , Estudos Transversais , Esmalte DentárioRESUMO
A repetitive batch process was employed followed by membrane ultrafiltration system to produce low-cost cyclodextrins (CDs) using commercial enzymes Toruzyme® cyclomaltodextrin glucanotransferase (CGTase) and its kinetic parameters were determined. The ultrafiltration system enabled the removalof inhibitory products from the reaction medium, allowing the enzyme to be recovered for reuse. A 10 kDa membrane was used to separate the different CDs produced by the CGTase. The substrates evaluated were maltodextrin, corn starch and cassava starch at 5, 10 and 15% (w/V), in the presence and absence of 10% (V/V) ethanol. After reaction for 132 h, 10% (w/V) cassava starch in the presence of ethanol provided the best results with 32.1 mg/mL of ß-CD. Maximum production occurred after 72 h of reaction, with a yield of 87.4% of ß-CD and an α-CD, ß-CD and γ-CD production ratio of 1:1:0.08 g, respectively. When eight repetitive batches of 72 h followed by ultrafiltration and crystallization of ß-CD were performed, 2.1 g of precipitate was obtained with a purity of 67.6% ß-CD. The supernatant from the crystallization process was lyophilized and resulted in 35.3% α-CD. The developed model can be used industrially for the production of low cost CDs from easily obtained raw material
Assuntos
Ultrafiltração/instrumentação , Modelos Econômicos , Tecnologia de Baixo Custo/análise , Ciclodextrinas/farmacologia , Amidos e Féculas , Cristalização/classificaçãoRESUMO
Temozolomide, a chemotherapeutic drug that is often administered for the treatment of brain cancer has severe side effects and a poor aqueous solubility. In order to decrease the detrimental effect of the drug over healthy cells, a novel drug delivery vehicle was developed where the therapeutic drug was encapsulated within the hydrophobic cavities of b-CD modified magnetite nanoparticles, which are embedded in chitosan nanobeads prepared by salt addition. In-vitro studies have shown that the magnetic properties of the novel delivery vehicle are adequate for targeted drug delivery applications under an external magnetic field. Additionally, an increase in the amount of chitosan was shown to exhibit a strong shielding effect over the magnetic properties of the delivery vehicle, which lead to deterioration of the amount of captured drug at the targeted area, suggesting a delicate balance between the amounts of constituents composing the drug delivery vehicle.
Assuntos
Técnicas In Vitro/instrumentação , Neoplasias Encefálicas , Temozolomida/análise , Preparações Farmacêuticas/administração & dosagem , Ciclodextrinas/farmacologia , Quitosana/antagonistas & inibidores , Óxido Ferroso-Férrico/farmacologia , Nanopartículas de Magnetita/efeitos adversos , Campos Magnéticos/efeitos adversos , Magnetismo/classificaçãoRESUMO
Albendazole and fenbendazole are imidazole derivatives that exhibit broad spectrum activity against parasites, but the low solubility of these drugs considerably reduces their effectiveness. Complexation of albendazole and fenbendazole with cyclodextrins (ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin) in both water and an aqueous solution of polyvinylpyrrolidone (PVP-k30) was studied to determine if it could increase the solubility and dissolution rate of the drugs. In an aqueous solution, ß-cyclodextrin increased the solubility of albendazole from 0.4188 to ~93.47 µg mL-1 (223×), and of fenbendazole from 0.1054 to 45.56 µg mL-1 (432×); hydroxypropyl-ß-cyclodextrin, on the other hand, increased solubility to ~443.06 µg mL-1 (1058×) for albendazole and ~159.36 µg mL-1 (1512×) for fenbendazole. The combination of hydroxypropyl-ß-cyclodextrin and polyvinylpyrrolidone enabled a solubility increase of 1412× (~591.22 µg mL-1) for albendazole and 1373× (~144.66 µg mL-1) for fenbendazole. The dissolution rate of the drugs was significantly increased in binary and ternary systems, with hydroxypropyl-ß-cyclodextrin proving to be more effective. The presence of the water-soluble PVP-k30 increased the dissolution rate and amorphization of the complexes. Analysis of the changes in displacement and the profile of the cyclodextrin bands in the 1H NMR spectra revealed a molecular interaction and pointed to an effective complexation in the drug/cyclodextrin systems. Monomeric forms and nanoclusters of cyclodextrins were observed in the drug/cyclodextrin systems, suggesting that the increase in solubility of the drugs in the presence of cyclodextrins should not be attributed only to the formation of inclusion complexes, but also to the formation of cyclodextrin aggregates
Assuntos
Benzimidazóis/administração & dosagem , Ciclodextrinas/farmacocinética , Dissolução/classificação , Solubilidade , Preparações Farmacêuticas , Albendazol/análise , Fenbendazol/análise , Antiparasitários/análiseRESUMO
Nesta pesquisa avaliou-se o efeito do colesterol sobre o sêmen de garanhões da raça Nordestina sobre a qualidade espermática. Vinte ejaculados de dois garanhões foram diluídos com BotuSemen e colesterol carreado pela ciclodextrina (CCC) adicionado no sêmen: controle, 0,75mg de CCC e 1,0mg de CCC/120x106 sptz/mL, e incubado a 26°C/15min. O sêmen foi diluído 1:5 (v/v) com diluente Lactose-gema de ovo e resfriado a 5°C/2h, envasado em palhetas de 0,5mL, e acondicionado sob vapor de nitrogênio líquido, e depois imersos. As amostras foram descongeladas (37 °C/30s) e avaliadas. As variáveis foram avaliadas com ANOVA e teste de Tukey (P<0,05). A motilidade total e progressiva foi maior (P<0,05) no sêmen tratado com CCC comparado as amostras do grupo controle, e CCC promoveu maior percentual (P<0,05) de motilidade total e progressiva durante as 3 horas de incubação. A percentagem de espermatozoides com viabilidade e integridade foi maior (P<0,05) no sêmen tratado com CCC (81,47 e 86,07%) comparado ao controle (72,12 e 70,19%). O número de espermatozoides reativos ao teste hiposmótico foi maior (P<0,05) nas amostras de sêmen tratadas com CCC comparado ao controle. Adição de colesterol no sêmen de garanhões Nordestino melhora a qualidade espermática apos a criopreservação.(AU)
In the study effect of cholesterol was evaluated on the sperm quality of Nordestina stallion breed. Twenty semen samples were used from two stallions, diluted with BotuSemen extender and cholesterol add as follows: control, 0.75mg of cholesterol-loaded cyclodextrin (CLC) and 1.0mg of CLC/120x106 sperm/mL, and incubated for 15 min at 22°C. The samples were diluted 1:5 with lactose-yolk egg extender and cooled to 5°C over two hours, loaded into 0.5mL straws and frozen in static liquid nitrogen vapor before being plunged into nitrogen. Samples were thawed (37°C/30s) and analyzed. The variables were analyzed by ANOVA and means compared by Tukey test (P<0.05). Higher percentages of total and progressive motile was higher for sperm treated with CLC compared to control, and CLC promoted higher percentages (P<0.05) of total and progressive motility for the 3 hours of incubation. The percentage of viability and plasma membrane integrity of spermatozoa were higher (P<0.05) in sperm treated with CLC compared to the control group. The number of spermatozoa reacted to hypoosmotic test was higher (P<0.05) in sperm treated with CLC than control. Addition of CLC in the semen of Nordestina stallion breed improve the sperm quality after cryopreservation.(AU)
Assuntos
Animais , Preservação do Sêmen/veterinária , Colesterol/administração & dosagem , Ciclodextrinas/análise , LongevidadeRESUMO
ABSTRACT Temozolomide is a poorly soluble anti-cancer drug used in the treatment of some brain cancers. Following literature reports about the enhancement of solubility and stability for these kinds of drugs upon complexation with cyclodextrins, we aimed to form an inclusion complex between temozolomide and the different types of cyclodextrins (CDs) to enhance its solubility. In this study, three different cyclodextrins (ß -CD, hydroxyl-ß-CD and γ-CD) were used, and changes in solubility was measured by UV-Vis Spectroscopy and HPLC. Morphological changes upon complexation were shown by the Scanning Electron Microscope (SEM), and weight loss profiles with respect to temperatures which were unique to the compounds were shown by Thermogravimetric Analysis. Changes in heat release profiles were shown by Differential Scanning Calorimeter (DSC). Drug solubility was measured to be increased to around 25% for 1:1 molar ratio for all used CD complexations. Changes of morphology, heat release and weight loss profiles are consistent with the formation of an inclusion complex between CDs and temozolomide. In this study, success was shown in the enhancement of temozolomide solubility upon complexation with different types of CDs. It has been demonstrated that cyclodextrins can be used as complexing agents for poorly soluble anti-cancer drugs, increasing their solubility and hence drug availability
Assuntos
Solubilidade , Anticarcinógenos/análise , Ciclodextrinas/efeitos adversos , Preparações Farmacêuticas , Microscopia Eletrônica de Varredura/métodosRESUMO
A radiação UV pode causar danos à pele humana, e, evitar estes danos, é uma preocupação crescente para a população e um desafio à comunidade científica. Para uma ação efetiva de fotoproteção, a associação de filtros, como avobenzona (BMBM) e ρ-metoxicinamato de octila (EHMC), são empregados. Devido à semelhança estrutural com os filtros solares químicos, a rutina (RUT), tal como outros flavonoides, apresenta atividade fotoprotetora. Apesar da disponibilidade de diferentes classes de filtros solares, o desenvolvimento de fotoprotetores contendo filtros químicos é um desafio, devido à instabilidade inerente a certos filtros orgânicos. As ciclodextrinas (CDs) são oligossacarídeos cíclicos, de formato tronco-cônico, cuja estrutura externa é hidrófilica e sua cavidade interna central hidrofóbica, com a capacidade de acomodar substâncias lipofílicas, formando complexos de inclusão. A formação dos complexos de inclusão pode levar à alterações de propriedades físico-químicas da molécula hóspede, tais como, solubilidade, fotoestabilidade e biodisponibilidade. O objetivo deste trabalho foi desenvolver, caracterizar e avaliar a formação de complexos de inclusão entre RUT, BMBM e EHMC e as CDs (HPßCD e SBEßCD). Os complexos de inclusão (RUT:HPßCD, RUT:SBEßCD, BMBM:HPßCD, BMBM:SBEßCD, EHMC:HPßCD e EHMC:SBEßCD) foram obtidos pelo método de liofilização e quantificados por cromatografia líquida de alta eficiência (CLAE). Os sistemas binários foram caracterizados em solução, pelo método de equilíbrio de solubilidade, e, no estado sólido, empregando calorimetria exploratória diferencial (DSC), termogravimetria (TG/DTG) e difração de raios-X de pó (PDRX). As substâncias isoladas e os complexos binários foram avaliados quanto à fotoestabilidade em estado sólido, e, em solução. Incremento na solubilidade (X mcg mL-1) foi observado para os complexo RUT:HPßCD (4,13x); RUT:SBEßCD (4,38x); BMBM:HPßCD (43,3x); BMBM:SBEßCD (53,3x); EHMC:HPßCD (12,7x); e EHMC:SBEßCD (70,0x). Os ensaios de DSC, TG/DTG, e P-DRX indicaram a formação de complexos de inclusão para os todos os sistemas, onde a supressão dos eventos endotérmicos característicos das substâncias isoladas foram observados; porém, nos complexos de BMBM, a presença de avobenzona livre no meio foi detectada, sugerindo, que a complexação não foi completa. A formação dos complexos de inclusão promoveu o aumento da fotoestabilidade em todos os sistemas avaliados, tanto no estado sólido, como em solução. Os resultados reportados neste estudo, indicaram que a complexação de substâncias fotoprotetoras com HPßCD e SBEßCD, pode representar, uma estratégia promissora quanto ao aumento da solubilidade e da fotoestabilidade
UV radiation may cause demage on human skin, and preventing it, is an increasing worry for the population and a challenge to the scientific community. For an effective action of photoprotection, the association of filters, like avobention (BMBM) and octyl ρ-methoxycinnamate (EHMC), are used. Due to the structural similarity with the chemical solar filters, the rutin (RUT), like other flavonoids, shows photoprotective activity. Despite the availability of different classes of sunscreens, the development of photoprotectors containing chemical filters is a challenge, due to the inherent instability of certain organic filters. The cyclodextrins (CD) are cyclic oligosaccharides of truncated conical structure, which external structure is hydrophilic and its internal central hydrophobic cavity, with capacity to accommodate lipophilic substances, forming inclusion complexes. The formation of the inclusion complexes can lead to changes in physicalchemical properties of the host molecule, such as, solubility, photostability and bioavailability. The objective of this work was to develop, characterize and evaluate the formation of the inclusion complexes between RUT, BMBM and EHMC and the CDs (HPßCD and SBEßCD). The inclusion complexes (RUT:HPßCD, RUT:SBEßCD, BMBM:HPßCD, BMBM:SBEßCD, EHMC:HPßCD and EHMC:SBEßCD) were obtained by the lyophilization method and quantified by high performance liquid chromatography (HPLC). The binary systems were characterized in solution, by solubility equilibrium method and in solid state, using differential scanning calorimetry (DSC), thermogravimetry (TG/DTG) and powder X-ray diffraction (P-XRD). The isolated substances and binary complexes were evaluated the photostability in solid state, and in solution. The increase in solubility (X mcg mL-1) was observed for the complexes RUT:HPßCD (4.13x); RUT:SBEßCD (4.38x); BMBM:HPßCD (43.3x); BMBM:SBEßCD (53.3x); EHMC:HPßCD (12.7x); and EHMC:SBEßCD (70.0x). The analysis of DSC, TG/DTG, and P-DRX indicated the formation of inclusion complexes for all systems, where the suppression of the endothermic events characteristic of the isolated substances were observed; however, in the BMBM complexes, the presence of free avobenzone was detected, suggesting that the complexation was not complete. The formation of inclusion complexes promoted the increase of photostability in all evaluated systems, as in solid state as in solution. The results reported in this study indicated that the complexation of photoprotective substances with (HPßCD e SBEßCD). may represent a promising strategy for increasing solubility and photostability
Assuntos
Rutina/análise , Ciclodextrinas , Oligossacarídeos/classificação , Protetores Solares , Termogravimetria/métodos , Raios Ultravioleta , Varredura Diferencial de Calorimetria , Cromatografia Líquida de Alta Pressão/métodos , Liofilização/métodosRESUMO
ABSTRACT This study aimed to improve the water solubility of amiodarone hydrochloride (AMH) via inclusion complexes with β-cyclodextrin, methyl-β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin. Inclusion complexes were developed by physical mixture, coevaporation, spray-drying and freeze-drying. Solid state analysis was performed using X-ray powder diffraction, differential scanning calorimetry and scanning electronic microscopy. Thermodynamic studies demonstrate that the inclusion complexes of drug into different cyclodextrins were an exothermic process that occurred spontaneously. Water solubility and drug dissolution rates were significantly increased after the formation of inclusion complexes with the cyclodextrins evaluated in relation to the physical mixture and pure drug. The present study provides useful information for the potential application of complexation with amiodarone HCl. This may be a good strategy for the development of solid pharmaceutical dosage forms.
Assuntos
Ciclodextrinas/farmacologia , /análise , Dissolução/análise , Amiodarona/farmacologia , SolubilidadeRESUMO
Estratégias amplamente utilizadas para potencializar os efeitos citotóxicos de moléculas antitumorais com o objetivo de reduzir a dose aplicada e os efeitos colaterais são a inclusão molecular e a associação da quimioterapia com a hipertermia. No presente trabalho foram estudadas estas duas estratégias, sendo a primeira a inclusão molecular que é muito utilizada para aumentar a solubilidade, a absorção e a disponibilidade de moléculas; e a segunda, a hipertermia que é uma proposta de tratamento do câncer no qual as células do tumor são afetadas pela elevação da temperatura local, podendo ser associada com a quimioterapia para potencializar os efeitos dessa técnica. Para a inclusão molecular usou-se a hidroxipropil-¿-ciclodextrina (HP-¿-CD) a fim de aumentar a solubilidade, a absorção e a disponibilidade do erlotinibe (ERL), caracterizou-se fisico-quimicamente, e avaliou-se a citotoxicidade e a apoptosein vitro, e a angiogênese inflamatória in vivo em camundongos Swiss. Para avaliar o efeito citotóxico da hipertermia (aquecimento a 42°C ou 43°C por 1h) associada à cisplatina utilizou-se linhagens de câncer de mama triplo-negativos (MDA-MB-231, MDA-MB-436, MDA-MB-468 e HCC-1937), linhagens de câncer de colo do útero (ME-180 e SiHa) e linhagens de câncer de pulmão (A549 e H460). A caracterização físico-química mostrou a formação do complexo de inclusão em estado sólido e aquoso, e com uma razão molar entre o ERL e HP-¿-CD preferencialmente de 1:1. O estudo de solubilidade de fases mostrou um diagrama do tipo AL e a calorimetria de titulação isotérmica e a espectrometria de ressonância magnética nuclear, efeito Overhauser nuclear suportam essa formação...
Strategies widely used to potentiate the cytotoxic effects of antitumor molecules with the aim of reduce the applied dose and side effects are molecular inclusion and the combination of chemotherapy with hyperthermia. In this thesis, these two strategies were studied, the first molecular inclusion that is widely used to enhance solubility, absorption and availability molecules; and the second, hyperthermia which is a proposal for treatment of cancer where the tumor cells are affected by local temperature elevation and can be associated with chemotherapy to enhance the effects of this technique. For molecular inclusion used to hydroxypropyl--cyclodextrin (HP--CD) to enhance solubility, absorption and availability of erlotinib (ERL), was characterized physico chemically and evaluated the in vitro cytotoxicity and apoptosis, and in vivo inflammatory angiogenesis in Swiss mice. To evaluate the cytotoxic of hyperthermia (heating to 42°C or 43°C for 1h) associated with cisplatin was used triple-negative breast cancer cell lines (MDA-MB-231, MDA-MB-436, MDA-MB-468 and HCC-1937), cervical cancer cell lines (ME-180 and SiHa) and lung cancer cell lines (A549 and H460). The physico-chemical characterization showed the formation of the inclusion complex in solid and aqueous state and with a molar ratio between the ERL and HP--CD preferably 1:1. Phase-solubility ...
Assuntos
Animais , Camundongos , Ciclodextrinas , Hipertermia Induzida , Neoplasias/terapia , Tratamento Farmacológico , Temperatura Alta/uso terapêutico , Apoptose , Citotoxinas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Solubilidade/efeitos da radiação , Células Tumorais Cultivadas , Técnicas In VitroRESUMO
Platinum-based anticancer drugs have been becoming one of the most effective drugs for clinical treatment of malignant tumors for its unique mechanism of action and broad range of anticancer spectrum. But, there are still several problems such as side effects, drug resistance/cross resistance and no-specific targeting, becoming obstacles to restrict its expanding of clinical application. In recent years, supramolecular chemistry drug delivery systems have been gradually concerned for their favorable safety and low toxicity. Supramolecular macrocycles-platinum complexes increased the water solubility, stability and safety of traditional platinum drugs, and have become hot focus of developing novel platinum-based anticancer drugs because of its potential targeting of tumor tissues/organs. This article concentrates in the research progress of the new drug delivery system between platinum-based anticancer drugs with three generations of macrocycles: crown ether, cyclodextrin, cucurbituril and calixarene.
Assuntos
Humanos , Antineoplásicos , Farmacologia , Calixarenos , Coronantes , Ciclodextrinas , Sistemas de Liberação de Medicamentos , Compostos Macrocíclicos , Farmacologia , Neoplasias , Tratamento Farmacológico , Compostos de Platina , FarmacologiaRESUMO
Carvedilol is administered as a racemic mixture of the R[+]- and S[-]-enantiomers, although it was demonstrated that the two enantiomers exhibit different pharmacological effects and stereoselective pharmacokinetics. The aim of this study was the evaluation of several native and derivatized cyclodextrines as chiral selectors for the separation of carvedilol enantiomers. Stereoselective interactions were observed with four cyclodextrines [beta-CD, hydroxypropyl-beta-CD, randomly methylated beta-CD and sulfobuthyl ether-beta-CD]. The effects of CD concentration, pH value and composition of the background electrolyte, capillary temperature, running voltage and injection parameters have been investigated. The method was validated for precision of peak-area response, linearity range and limits of detection and quantification. An efficient stereoselective capillary zone electrophoretic method was developed for the determination of carvedilol enantiomers using a simple 25 mM phosphate buffer at a pH = 2.5 and 10 mM beta-CD as chiral selector, resulting in baseline separation of the two enantiomers with sharp peaks and relatively short analysis time. Highly satisfactory results were obtained from the analysis of carvedilol from tablets, indicating that the method is suitable for routine analysis of carvedilol in pharmaceutical products
Assuntos
Propanolaminas , Ciclodextrinas , Eletroforese CapilarRESUMO
A alveolite seca (AS) é uma das complicações pós-operatórias mais comuns e sintomáticas na odontologia, porém, até o momento não há um protocolo de tratamento definido. O composto fenólico guaiacol (Gu) é um dos materiais utilizados para revestimento intra-alveolar devido às suas propriedades analgésicas, antioxidantes e antimicrobianas. Contudo, sua desvantagem é a dificuldade de manipulação decorrente da sua baixa estabilidade, alta volatilidade e sensibilidade à oxidação. Para melhorar suas propriedades e aumentar sua aplicabilidade clínica, um complexo de inclusão de Gu com ß-ciclodextrina (ßcd) foi desenvolvido. A formação do complexo supramolecular de Gu:ßcd foi caracterizada mediante a ressonância magnética nuclear (RMN), nos experimentos de 1H e 2D ROESY. A atividade antibacteriana do Gu e Gu:ßcd frente a Escherichia coli, Staphylococcus aureus, Streptococcus mitis, Streptococcus mutans, Streptococcus sanguis e Aggregatibacter actinomycetemcomitans foi analisada pelo método da microdiluição e sua citotoxicidade em osteoblastos de calvária de rato, foi estudado com o ensaio do MTT. O processo de reparo alveolar induzido pelo Gu:ßcd foi avaliado histologicamente após tratamento de alveolite seca em molares inferiores de ratos. A RMN mostrou correlações espaciais entre os hidrogênios internos (H3 e H5) da ßcd e os hidrogênios aromáticos, H(a) e H(b) do Gu, confirmando a formação do complexo. A complexação do Gu na ßcd potencializou seu efeito antibacteriano e reduziu sua citotoxicidade em osteoblastos. O estudo in vivo evidenciou a ocorrência de ossificação no ápice alveolar dos ratos tratados com Gu:ßcd, no 7o dia. No 14o dia, as trabéculas ósseas ocuparam também o terço médio do alvéolo e no 21o dia, todo o alvéolo se encontrava preenchido por osso neoformado. Estes resultados foram similares ao controle negativo e superiores ao controle positivo (Alvogyl®). Os benefícios obtidos pela inclusão do Gu na ßcd foram demonstrados pela melhora das...
Dry socket is one of the most common and symptomatic complications in dentistry, however, there is still not a settled treatment for this condition. The phenolic compound guaiacol (Gu) is one of several alveolar dressings used in dry socket because it has analgesic, antioxidant and antimicrobial properties. Nevertheless, its disadvantage is the difficulty of manipulation due to its low stability, high volatility and sensitivity to oxidation. To improve its properties and increase its clinical applicability, an inclusion complex of Gu with ß-cyclodextrin (ßcd) was developed. The Gu:ßcd supramolecular complex was characterized by Nuclear Magnetic Ressonance (NMR), in the 1H and 2D ROESY experiments. The antibacterial activity of Gu and Gu:ßcd over Escherichia coli, Staphylococcus aureus, Streptococcus mitis, Streptococcus mutans, Streptococcus sanguis and Aggregatibacter actinomycetemcomitans was analyzed using the microdilution method and its cytotoxicity in rat calvaria-derived osteoblast was evaluated with the MTT assay. The alveolus repair process induced by Gu:ßcd was histologically studied after the treatment of dry socket in rat mandibular molars. The NMR showed spatial correlations between internal hydrogens (H3 and H5) of ßcd and aromatic hydrogens, H(a) and H(b), of Gu confirming the inclusion complex formation. Gu:ßcd complex potentiated Gu antibacterial effect and reduced its cytotoxicity in osteoblasts. The in vivo study revealed that ossification occurred in the alveolar apex of rats treated with Gu:ßcd, by day 7. In the 14th day, the trabecular bone occupied the apical and middle thirds of the socket and on the 21st day, the entire alveolus was filled by newly formed bone. These results were similar to the negative control and superior to the positive control (AlvogylTM). Benefits gained from inclusion of Gu in cyclodextrin have been particularly demonstrated by the improvement in Gu biological properties in vitro and the appropriate alveolus...
Assuntos
Humanos , Masculino , Feminino , Alvéolo Seco/complicações , Alvéolo Seco/diagnóstico , Alvéolo Seco/metabolismo , Ciclodextrinas/análise , Ciclodextrinas/efeitos adversos , Ciclodextrinas/normas , Guaiacol/análise , Guaiacol/efeitos adversosRESUMO
Objetivo. Estimar el calendario de inicio sexual en México y sus tendencias a partir de encuestas poblacionales. Material y métodos. Se analizaron cinco cohortes de nacimiento con cuatro encuestas nacionales (Encuesta Nacional de Salud 2000, Encuesta Nacional de la Dinámica Demográfica 2009, Encuesta Nacional de Juventud 2010 y Encuesta Nacional de Salud y Nutrición 2012) y se identificaron las proporciones de individuos que iniciaron actividad sexual antes de los 16 y antes de los 20 años. Resultados. Las distintas encuestas son, en general, consistentes, pero difieren entre ellas en algunas cohortes. En las cohortes más jóvenes, se identificó una proporción algo mayor de individuos que iniciaron antes de los 20 años; no se advierten cambios en el inicio sexual antes de los 16 años. Conclusiones. La falta de grandes cambios en la edad de inicio de vida sexual con tendencia al adelanto del calendario en México llama a fortalecer la educación sexual integral y la oferta de servicios de salud sexual y reproductiva accesibles a los adolescentes.
Objective. To estimate calendar of sexual debut in Mexico and its trends using national representative household surveys. Materials and methods. Analysis of five birth cohorts extracted from four national population based household surveys in Mexico (National Health Survey 2000, National Survey on Demographic Dynamics 2009, National Youth Survey 2010, and National Health & Nutrition Survey 2012), using as outcome the proportion of individuals that reported sexual debut before the age of 16 and before the age of 20. Results. Overall, the four analyzed surveys produce consistent results, although some differences were found. While a larger proportion among younger cohorts reported sexual debut before the age of 20, that was not the case for sexual debut before 16 years. Conclusions. While data seems to reflect a relative stable age of sexual debut in Mexico, there is a recent trend to prepone sexual initiation that highlights the need to strengthen comprehensive sexual education and the supply of sexual & reproductive health services that are accessible and friendly to adolescents thus responding to the growing demand from this age group.
Assuntos
Animais , Feminino , Masculino , Camundongos , Ratos , Anti-Inflamatórios não Esteroides/farmacologia , Benzenoacetamidas , Ciclodextrinas/farmacologia , Ácidos Hidroxâmicos/farmacologia , Ibuprofeno/farmacologia , beta-Ciclodextrinas , Anti-Inflamatórios não Esteroides/síntese química , Ciclodextrinas/química , Modelos Animais de Doenças , Combinação de Medicamentos , Mucosa Gástrica/efeitos dos fármacos , Ácidos Hidroxâmicos/química , Inflamação/tratamento farmacológico , Contração Muscular/efeitos dos fármacos , Medição da Dor/efeitos dos fármacos , EstereoisomerismoRESUMO
Geraniol (GR) is an acyclic monoterpene alcohol present in essential oils of aromatic plant species used in Brazilian folk medicine for the treatment of epilepsy. The present study was designed to evaluate the anticonvulsant effect of GR and of the inclusion complex geraniol:beta-cyclodextrin (GR:beta-CD). Mice were treated with GR or with GR:beta-CD (50, 100 and 200 mg/kg) 30 min before pentylenetetrazole (PTZ) or strychnine (STN). GR at 200 mg/kg and GR:beta-CD at the doses of 100 and 200 mg/kg significantly increased the latency for the first PTZ-induced convulsion and reduced the percentage of animals that convulsed. The pretreatment of flumazenil did not revert the anticonvulsant effect of GR in the PTZ-induced convulsion model. In the STN-induced convulsion model, the effects of GR were investigated and no difference was found against control. The results demonstrated an anticonvulsant activity of GR in the PTZ-model, which was potentialized by the complexation with beta-CD...
Geraniol (GR) es un alcohol monoterpeno acíclico presentes en los aceites esenciales de las especies de plantas aromáticas utilizadas en la medicina popular brasileña para el tratamiento de la epilepsia. El presente estudio fue diseñado para evaluar el efecto anticonvulsivo del GR y de la inclusión de geraniol complejo: beta-ciclodextrina (GR:beta-CD). Los ratones fueron tratados con GR o con GR:beta- CD (50, 100 y 200 mg/kg) 30 minutos antes de pentylenotetrazole (PTZ) o strichinine (STN). GR a 200 mg/kg y GR:beta-CD en las dosis de 100 y 200 mg/kg aumentó significativamente la latencia para la primera convulsión inducida PTZ-y redujo la porcentaje de animales que convulsionó. El tratamiento previo de flumazenil no revirtió el efecto anticonvulsivo de GR en el modelo de convulsión inducida con PTZ. En el modelo de convulsión inducida com STN, los efectos de GR fueron investigados y no se encontró ninguna diferencia contra el control. Los resultados demostraron una actividad anticonvulsiva de geraniol en el modelo de PTZ, que fue potenciada por la formación de complejos con beta-CD...
Assuntos
Animais , Camundongos , Óleos Voláteis/administração & dosagem , Anticonvulsivantes/administração & dosagem , Epilepsia/tratamento farmacológico , Terpenos/administração & dosagem , Ciclodextrinas , Fármacos Neuroprotetores/administração & dosagem , Monoterpenos/administração & dosagem , Pentilenotetrazol/administração & dosagemRESUMO
Background Cyclodextrin glucanotransferase (CGTase) from Amphibacillus sp. NPST-10 was covalently immobilized onto amino-functionalized magnetic double mesoporous core-shell silica nanospheres (mag@d-SiO2@m-SiO2-NH2), and the properties of the immobilized enzyme were investigated. The synthesis process of the nanospheres included preparing core magnetic magnetite (Fe3O4) nanoparticles, coating the Fe3O4 with a dense silica layer, followed by further coating with functionalized or non-functionalized mesoporous silica shell. The structure of the synthesized nanospheres was characterized using TEM, XRD, and FT-IR analyses. CGTase was immobilized onto the functionalized and non-functionalized nanospheres by covalent attachment and physical adsorption. Results The results indicated that the enzyme immobilization by covalent attachment onto the activated mag@d-SiO2@m-SiO2-NH2, prepared using anionic surfactant, showed highest immobilization yield (98.1%), loading efficiency (96.2%), and loading capacity 58 µg protein [CGTase]/mg [nanoparticles]) which were among the highest yields reported so far for CGTase. Compared with the free enzyme, the immobilized CGTase demonstrated a shift in the optimal temperature from 50°C to 50-55°C, and showed a significant enhancement in the enzyme thermal stability. The optimum pH values for the activity of the free and immobilized CGTase were pH 8 and pH 8.5, respectively, and there was a significant improvement in pH stability of the immobilized enzyme. Moreover, the immobilized CGTase exhibited good operational stability, retaining 56% of the initial activity after reutilizations of ten successive cycles. Conclusion The enhancement of CGTase properties upon immobilization suggested that the applied nano-structured carriers and immobilization protocol are promising approach for industrial bioprocess for production of cyclodextrins using immobilized CGTase.