An injectable hydrogel/staple fiber composite for sustained release of CA4P and doxorubicin for combined chemotherapy of xenografted breast tumor in mice / 南方医科大学学报

OBJECTIVE@#To prepare an injectable hydrogel/staple fiber composite loaded with combretastain A-4 disodium phosphate (CA4P) and doxorubicin (DOX) and evaluate its antitumor efficacy via intratumoral injection.@*METHODS@#DOX-loaded PELA staple fibers (FDOX) were prepared using electro-spinning and cryo-cutting, and the drug distribution on the surface of the fibers was observed using a fluorescence microscope, and the encapsulation efficiency and loading capacity of FDOX were determined with a fluorospectro photometer. The fibers were then dispersed in CA4P-loaded PLGA-PEG-PLGA tri-block polymer solution at room temperature to obtain the hydrogel/staple fiber composite (GCA4P/FDOX). The thermo-sensitivity of this composite was determined by a test tube inverting method. An ultraviolet spectrophotometer and a fluorospectrophotometer were used to detect the release profile of CA4P and DOX, respectively. We observed in vivo gel formation of the composite after subcutaneous injection in mice. The in vitro cytotoxicity of GCA4P/FDOX composite in MCF-7 and 4T1 cells was assessed using cell Counting Kit-8 (CCK-8) reagent. In a mouse model bearing breast tumor 4T1 cell xenograft, we evaluated the antitumor efficacy of the composite by monitoring tumor growth within 30 days after intratumoral injection of the composite. HE staining, immunohistochemistry for Ki67 and immunofluorescence (TUNEL) assay were used for pathological examination of the tumor tissues 21 days after the treatments.@*RESULTS@#The average length of FDOX was 4.0±1.3 μm, and its drug loading capacity was (2.69±0.35)% with an encapsulation efficiency of (89.70±0.12)%. DOX was well distributed on the surface of the fibers. When the temperature increased to 37 ℃, the composite rapidly solidified to form a gel in vitro. Drug release behavior test showed that CA4P was completely released from the composite in 5 days and 87% of DOX was released in 30 days. After subcutaneous injection, the composite solidified rapidly without degradation at 24 h after injection. After incubation with GCA4P/FDOX for 72 h, only 30.6% of MCF-7 cells and 28.9% of 4T1 cells were viable. In the tumor-bearing mice, the tumor volume was 771.9±76.9 mm3 in GCA4P/FDOX treatment group at 30 days. Pathological examination revealed obvious necrosis of the tumor tissues and tumor cell apoptosis induced by intratumoral injection of G4A4P/FDOX.@*CONCLUSION@#As an efficient dual drug delivery system, this hydrogel/staple fiber composite provides a new strategy for local combined chemotherapy of solid tumors.

Eficacia del indacaterol como broncodilatador en un grupo de pacientes asmáticos / Effectiveness of Indacaterol as bronchodilator in a group of asthmatic patients

La búsqueda de nuevas opciones terapéuticas para tratar las enfermedades obstructivas bronquiales representa un reto permanente y los broncodilatadores constituyen unos de los fármacos más empleados para la atención de estos pacientes. En los últimos años han ido ganando fuerza los broncodilatadores de acción prolongada, pero el mayor efecto alcanzado era 12 h, superado por un broncodilatador nuevo salido al mercado en el año 2011, denominado indacaterol, del grupo de los beta agonistas, se diferencia de estos por la duración de su efecto que llega a alcanzar 24 h. Se realizó un estudio prospectivo, a ciego, tipo ensayo clínico, aleatorizado, con 90 pacientes asmáticos, entre 18 y 59 años de edad, que acudieron al departamento de pruebas funcionales respiratorias para estudiarles la función pulmonar. Todos recibieron de manera aleatoria indacaterol, salbutamol o placebo, y se les repitió la espirometría a los 15 min y a las 24 h de aplicado cada medicamento. Se evidenció que la respuesta broncodilatadora obtenida en los que usaron indacaterol, a las 24 h, fue muy superior a la respuesta de los que usaron otros fármacos. Se muestra además un discreto aumento de la frecuencia cardiaca y de la tensión arterial en los que usaron indacaterol y salbutamol, principalmente a los 15 min de empleados dichos medicamentos, pero dentro de los límites considerados como normales. No se evidenciaron efectos adversos

The search for new therapeutic options to treat bronchial obstructive diseases represents a permanent challenge and bronchodilators constitute one of the most used drugs in the treatment of these patients. In recent years, long acting bronchodilators have grown importance, but the greatest effect has been 12 h, superseded by a new bronchodilator that came on to the market in the year 2011 named Indacaterol, which belongs to the group of ß2-agonists and differentiates from the rest for its effect on the duration which lasts 24 hours. A randomized, essay-type, blind, prospective study was performed in 90 asthmatic patients, ranging from 18 to 59 years of age that presented to the department of respiratory functional tests for a study of their pulmonary functions. All the patients randomly received Indacaterol, Salbutamol or Placebo and spirometry was repeated 15 minutes and 24 hours after treatment. It was evidenced that the bronchodilator response obtained at the 24 hours in those patients that used Indacaterol, was higher than the response in the patients that used other drugs. The patients that used Indacterol and Salbutamol also showed a discrete increase of the cardiac frequency and blood pressure, mainly 15 minutes after receiving such drugs, but this increase is considered within the normal limits. Adverse effects were not evidenced

Estudio de bioequivalencia entre dos productos: trimebutina de liberación prolongada de laboratorios Leti SAV vs debridat AP® de laboratorios Pfizer, luego de administar una dosis única de 300 mg en voluntarios sanos / Bioequivalence study of two products trimebutine extended release vs debridat SAV Leti laboratories AP Pzizer after administering a single dose of 300 mg in healthy volunteers

El objetivo del estudio fue evaluar la bioequivalencia entre dos formulaciones de liberación prolongada de trimebutina 300 mg, luego de una administración única en voluntarios sanos, a través de la determinación de su metabolito activo la desmetil-trimebutina. Se trata de un estudio abierto, randomizado, balanceado, con control activo, de dosis simple, cruzado, con dos períodos separados por un período de descanso y secuencial, realizado en 12 voluntarios sanos de ambos sexos. Los voluntarios recibieron de acuerdo al esquema asignado por la aleatorización y en dos períodos, una dosis única por vía oral después de un ayuno de 10 horas, de un comprimido de una formulación conteniendo 300 mg de Trimebutina AP de Laboratorios LETI S.A.V., o del producto de referencia DEBRIDAT AP®, de Laboratorios Pfizer. Después de la última muestra de sangre del primer período hubo un tiempo de lavado de siete días, luego del cual los voluntarios que recibieron el producto test en el primer período recibieron el producto de referencia y viceversa. Las tomas de muestras se realizaron antes de la dosis (tiempo cero), 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 18 h, 24 h y 36 h. El análisis estadístico se realizó utilizando un paquete estadístico del programa Equiv test, empleándose el análisis de la varianza (ANOVA) de los parámetros cinéticos AUC 0-inf, AUC 0-36 h y Cmax y la aplicación de los intervalos de confianza para el 90%. En el análisis comparativo se tomaron los intervalos de confianza con el rango de referencia de 0.8-1.25%. Para la Trimebutina test los valores fueron: Cmax 1343.49 +/- 585.58, AUC 0-36 de 8197.19 +/- 3995.23 y AUC 0-inf de 8198.36 +/- 3995.3. Para la formulación de referencia los valores fueron de: Cmax 1023.99 +/- 587.57, AUC 0-36 7221.15 +/- 3211.97 y AUC 0-inf de 7225.97 +/- 3211.62 sin diferencias significativas entre los grupos...

The objective of this study is to assess the bioequivalence of two sustained release formulations of trimebutine 300 mg, after a single administration in healthy volunteers, through determination of the active metabolite desmethyl-trimebutine. This is an open, randomized, balanced, active controlled, single dose, crossover study with two periods separated by a rest period and sequentially, conducted in 12 healthy volunteers of both sexes. Volunteers were assigned according to the randomization scheme and two periods, a single oral dose after fasting for 10 hours, a tablet formulation containing 300 mg of trimebutine AP LETI SAV Laboratories, or product Reference DEBRIDAT AP®, Pfizer Laboratories. After the last blood sample of the first period there will be a wash time of seven days, after which the volunteers received the test product in the first period will received the reference product and viceversa. The sampling is performed: before dosing (time zero), 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 18 h, 24 h and 36 h. Statistical analysis was performed using a statistical package Equiv test program, using analysis of variance (ANOVA) of the kinetic parameters AUC 0-inf, AUC 0-36h and Cmax and application of confidence intervals for 90%. In the comparative analysis we used the confidence intervals with the reference range of 0.8-1.25%. For the Trimebutine test values were Cmax 1343.49 +/- 585.58, AUC 0-36 of 8197.19 +/- 3995.23 and AUC 0-inf 8198.36 +/- 3995.3. For the formulation of reference values were: Cmax 1023.99 +/- 587.57, AUC 0-36 7221.15 +/- 3211.97 y AUC 0-inf of 7225.97 +/- 3211.62 no significant differences between groups. This study found that the Cmax and AUC, its log-transformed means and confidence intervals 90% away from each other not less than 80% or over 125%, so that both products are considered bioequivalent and therefore interchangeable

Efetividade da bupropiona no tratamento de pacientes tabagistas com doença cardiovascular / Effectiveness of sustained-release bupropion in the treatment of smoker patients with cardiovascular disease

OBJETIVOS: Avaliar a efetividade e a tolerabilidade da bupropiona no tratamento de fumantes com doenças cardiovasculares atendidos em rotina de tratamento ambulatorial do tabagismo, e analisar as variáveis preditoras de sucesso ou fracasso. MÉTODOS: A bupropiona foi prescrita de forma exclusiva para tratamento do tabagismo em 100 pacientes cardiopatas durante 12 semanas. O seguimento foi de 52 semanas. As variáveis estudadas foram sexo, idade, número de cigarros, concentração de monóxido de carbono, escala de dependência de nicotina, escala de depressão, escala de ansiedade, consumo de álcool, número de diagnósticos adicionais ao tabagismo, eventos adversos, e consumo de medicamentos concomitantes à bupropiona. RESULTADOS: A taxa de sucesso depois de 12 semanas foi de 50 por cento e depois de 52 semanas, de 25 por cento. A análise de regressão logística revelou que o envelhecimento foi positivamente associado ao sucesso e que o agravo da condição clínica, observado pelo maior número de diagnósticos associados ao tabagismo, foi negativamente associado ao sucesso. CONCLUSÃO: A bupropiona mostrou-se segura e com boa efetividade no tratamento de fumantes portadores de doenças cardiovasculares, especialmente durante a fase de uso (semana 12).

OBJECTIVES: To evaluate the effectiveness of and tolerability to sustained-release bupropion, in smokers with cardiovascular diseases treated in a smoking cessation service, as well as to investigate variables predictive of success or failure in smoking cessation. METHODS: Sustained-release bupropion was prescribed to 100 current smokers with cardiovascular disease for 12 weeks. Patients were followed for 52 week. The variables studied were gender, age, number of cigarettes, exhaled carbon monoxide, nicotine dependence (Fagerstrom Tolerance Questionnaire), depression (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory), alcohol consumption (Alcohol Use Disorders Identification Test), number of diagnoses other than smoking, adverse events, and use of medications concomitantly with sustained-release bupropion. RESULTS: Abstinence rate was 50 percent at week 12 and 25 percent at week 52. The logistic regression analysis showed that ageing was positively associated with success, whereas the worsening of the condition, as verified by the presence of a higher number of other health conditions associated with smoking, was negatively associated with success. CONCLUSION: We conclude that the prescription of bupropion for smokers with cardiovascular diseases proved to be safe and effective, especially during the treatment period (week 12).

Reaçäo tecidual ao implante de um dispositivo de liberaçäo lenta (Periochip©) em dorso de rato albino / Tissue reaction at the implant of a slow release device (Periochip©) in albino rats

Os objetivos do presente trabalho foram verificar, através da revisäo da literatura, os resultados obtidos em estudos que utilizaram os dispositivos de liberaçäo lenta contendo clorexidina, assim como descrever a reaçäo tecidual ocorrida quando um dispositivo de liberaçäo lenta (PerioChip©) foi introduzido no tecido conjuntivo do dorso de ratos albinos. Foi possível constatar que o uso dos dispositivos de liberaçäo lenta contendo clorexidina representa um adjunto ao tratamento das doenças periodontais e, quando colocado no tecido conjuntivo do dorso do rato, provoca uma intensa reaçäo inflamatória

Sistema biomaterial-droga para la liberación controlada de antibióticos / Biomaterials drugs delivery system control of antibiotics

En el presente trabajo se recogen las principales características de los sistemas de liberación sostenida de medicamentos soportados en diferentes biomateriales y que son utilizados fundamentalmente en el tratamiento de lesiones óseas. Sobre la base de una revisión bibliográfica actualizada en este tema, se analizan en detalle los tipos de biomateriales más utilizados, así como las ventajas y desventajas que los mismos presentan en tal aplicación