Economic model for obtaining cyclodextrins from commercial cgtase

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

Targeting of temozolomide using magnetic nanobeads: an in vitro study

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.

Inclusion complex of amiodarone hydrochloride with cyclodextrins: preparation, characterization and dissolution rate evaluation

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.

Calendario de inicio sexual en México: Comparación entre encuestas nacionales y tendencias en el tiempo / Sexual debut in Mexico: a comparison of household national surveys

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.

Induction of tissue inhibitor of matrix metalloproteinase-2 by cholesterol depletion leads to the conversion of proMMP-2 into active MMP-2 in human dermal fibroblasts

Cholesterol is one of major components of cell membrane and plays a role in vesicular trafficking and cellular signaling. We investigated the effects of cholesterol on matrix metalloproteinase-2 (MMP-2) activation in human dermal fibroblasts. We found that tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) expression and active form MMP-2 (64 kD) were dose-dependently increased by methyl-beta-cyclodextrin (MbetaCD), a cholesterol depletion agent. In contrast, cholesterol depletion-induced TIMP-2 expression and MMP-2 activation were suppressed by cholesterol repletion. Then we investigated the regulatory mechanism of TIMP-2 expression by cholesterol depletion. We found that the phosphorylation of JNK as well as ERK was significantly increased by cholesterol depletion. Moreover, cholesterol depletion-induced TIMP-2 expression and MMP-2 activation was significantly decreased by MEK inhibitor U0126, and JNK inhibitor SP600125, respectively. While a low dose of recombinant TIMP-2 (100 ng/ml) increased the level of active MMP-2 (64 kD), the high dose of TIMP-2 (> or = 200 ng/ml) decreased the level of active MMP-2 (64 kD). Taken together, we suggest that the induction of TIMP-2 by cholesterol depletion leads to the conversion of proMMP-2 (72 kD) into active MMP-2 (64 kD) in human dermal fibroblasts.

Estudo dos compostos de inclusäo tipo hospedeiro-convidado entre a beta-ciclodextrina e a clorexidina: Avaliaçäo in vitro / Study of inclusion compound host: guest type between chlorexidine and ß-cyclodextrin. In vitro evaluation

A clorexidina é hoje, para a Odontologia, um antisséptico importante no controle da placa bacteriana e a gengivites. É, entretanto, fato imprescindível analisar seus efeitos colaterais, embora mínimos, bem como a curta substantividade para se obter uma melhor utilizaçäo. As ciclodextrinas têm sido usadas para melhorar as propriedades farmacológicas das drogas tais como a solubilidade, a estabilidade e biodisponibilidade. Este trabalho visou estudar os compostos de inclusäo (Cl) entre a ß-ciclodextrina e o cloridrato de clorexidina (Cx-di(HCL)), preparaçäo, caracterizaçäo, dissoluçäo a diferentes pHs e atividade microbiológica. Os Cl foram preparados pelos métodos de mistura física, co-precipitaçäo e liofilizaçäo. No difratograma de raios X (DRX) do composto de inclusäo liofilizado observou-se um padräo amorfo quando comparado ao cristalino da ß-ciclodextrina e do Cx-di (HCL) sugerindo a formaçäo do composto de inclusäo. Evidência desta inclusäo também foi observada no espectro infravermelho (IV) do composto de inclusäo liofilizado devido ao afinamento das bandas de estiramento na regiäo de 3500-3300 cmû e 1650- 1500 cmû, sugerindo a quebra de ligaçöes de hidrogênio na saída das moléculas de água da cavidade da BCD quando comparadas as mesmas bandas para a ß-ciclodextrina e a mistura mecânica...

Avaliaçäo da eficácia e da segurança do complexo beta-ciclodextrina piroxicam em afecçöes diversas com componente doloroso/inflamatório / Evaluation of the efficacy and safety of piroxicam beta-ciclodextrin complex in different conditions associated with pain/inflamation: 2and Brazilian multicentric study

Foi realizado o 2§ Estudo Multicêntrico com a utilizaçäo do complexo beta-ciclodextrina-piroxocam, envolvendo 901 médicos e 2.681 pacientes em diversos centros do país. Os 2.681 pacientes avaliáveis foram subdivididos em grupos para melhor determinaçäo dos parâmentros em estudo. Quanto à eficácia, o tratamento foi considerado pelo investigadores e pelos pacientes como ótimo e bom em 94,8 por cento e 94,4 por cento dos casos, respectivamente. O tratamento foi bem tolerado, sendo a tolerabiblidade considerada ótima e boa em 95,5 por cento dos casos. Efeitos adversos foram observados em 5,7 por cento dos casos, sem necessidade de interrupçäo dos pacientes na maioria deles. Epigastralgia foi o efeito adverso mais comum, embora com incidência baixa (2,3 por cento)

Antibacterial activity of ciprofloxacin-beta-cyclodextrin complex and its efficacy in dental implants.

Ciprofloxacin forms an inclusion complex with beta-cyclodextrin. The in vitro antibacterial activity of ciprofloxacin on E. coli and Staphylococcus aureus was found better on complexation. The complex was found very effective as a local antibacterial agent when used in dental implants. Significant reduction in the gingival index, probing pocket depth and microbial growth coupled with gain in attachment at the test site compared to control on the 14th day was observed when the implants containing 2.0 mg of the complex equivalent to 0.4 mg of ciprofloxacin was used in clinical trials.

Evidence for beta-galactosidase catalyzed hydrolysis of paranitrophenyl-beta-D-galactopyranoside anchored in cyclodextrins.

The absorption maximum of p-nitrophenol upon mixing with molar equivalents of alpha-cyclodextrin (alpha-CD) or hydroxypropyl-beta-cyclodextrin (HPB) showed nearly 5 nm shift to the longer wavelength region, indicative of complex formation, while beta-cyclodextrin (beta-CD), gamma-cyclodextrin (gamma-CD) and hydroxyethyl-beta-cyclodextrin (HEB) produced only a marginal shift of about 1-2 nm, suggestive of a weaker interaction. It has been shown by circular dichroism spectral studies that the aglycon part of p-nitrophenyl-beta-D-glycoside (PNPG) is also encapsulated by alpha-cyclodextrin. The encapsulated form of PNPG could be hydrolyzed by beta-galactosidase, the temperature and pH-optima for hydrolysis of anchored substrates being essentially identical to that of free substrate. However, small but consistent increase in Km values were obtained for alpha-cyclodextrin-, HEB- and HPB-anchored substrates. The kcat values also registered an increase for the HEB- and HPB-anchored substrates. However, there was no increase in kinetic efficiency (kcat/Km) of enzyme. The inhibition noted at higher concentrations of HEB- and gamma-cyclodextrin-anchored PNPG but not with o-nitrophenyl-beta-D-galactoside (ONPG)-cyclodextrin mixture suggests that PNPG-cyclodextrin complexes were responsible for the inhibition. Taken together, these results suggest that the enzyme catalyses the hydrolysis of anchored substrates.