Antiepileptic drug-loaded and multifunctional iron oxide@silica@gelatin nanoparticles for acid-triggered drug delivery.

The current study developed an innovative design for the production of smart multifunctional core-double shell superparamagnetic nanoparticles (NPs) with a focus on the development of a pH-responsive drug delivery system tailored for the controlled release of Phenytoin, accompanied by real-time monitoring capabilities. In this regard, the ultra-small superparamagnetic iron oxide@silica NPs (IO@Si MNPs) were synthesized and then coated with a layer of gelatin containing Phenytoin as an antiepileptic drug. The precise saturation magnetization value for the resultant NPs was established at 26 emu g-1. The polymeric shell showed a pH-sensitive behavior with the capacity to regulate the release of encapsulated drug under neutral pH conditions, simultaneously, releasing more amount of the drug in a simulated tumorous-epileptic acidic condition. The NPs showed an average size of 41.04 nm, which is in the desired size range facilitating entry through the blood-brain barrier. The values of drug loading and encapsulation efficiency were determined to be 2.01 and 10.05%, respectively. Moreover, kinetic studies revealed a Fickian diffusion process of Phenytoin release, and diffusional exponent values based on the Korsmeyer-Peppas equation were achieved at pH 7.4 and pH 6.3. The synthesized NPs did not show any cytotoxicity. Consequently, this new design offers a faster release of PHT at the site of a tumor in response to a change in pH, which is essential to prevent epileptic attacks.

Determinação simplificada de carbamazepina, fenitoína, fenobarbital e lamotrigina em plasma emonitoração terapêutica por HPLC/PDA / Simplified determination of carbamazepine, phenytoin,phenobarbital and lamotrigine in plasma and therapeuticmonitoring by HPLC/PDA

Carbamazepina, fenitoína, fenobarbital e lamotrigina são bem conhecidos como fármacos anticonvulsivantes usados para o tratamento da epilepsia. A utilização destes fármacos é associada a várias reações adversas, tornando necessário o controle terapêutico. Os ensaios foram realizados por meio de cromatografia líquida de alta eficiência e o método de extração utilizado foi o líquido-líquido. Os fármacos e o padrão interno de zolpidem foram separados por uma coluna de fase reversa (ACE5, C18150x 4,6 mm d.i.). A fase móvel constituída de acetonitrila (30%) e ácido cítrico/tampão fosfato pH 5,0 (70%) foi utilizada sob gradiente de fluxo de 0,7 a 1,2 mL/min e o comprimento de onda utilizado para a detecção dos analitos foi fixado em 210 nm. A técnica apresentou linearidade ao longo do intervalo de 0,5 a 20,0μg/mL para carbamazepina/lamotrigina e de 2,0 a 64,0 μg/mL, para fenitoina/fenobarbital com coeficiente de correlação linear maior que 0,98. As amostras de sangue foram obtidas de pacientes adultos com diagnóstico de epilepsia em acompanhamento no Ambulatório Municipal de Psiquiatria de Goiânia. A média de recuperação obtida foi de 96,8% a 108,5% para carbamazepina/lamotrigina e de 93,8% a 108,8% para a fenitoina/fenobarbital. Os limites de quantificação, precisão (CV< 15,0 %)e exatidão (E > 85,0 %) demonstraram estar em conformidade com as exigências da ANVISA. Nove pacientes foram avaliados para confirmar a validade do método.

Carbamazepine, phenytoin, phenobarbital and lamotrigine are well known anticonvulsant drugs used in the treatment of epilepsy. However, these medications are associated with side effects and therefore require therapeutic monitoring. Blood samples of adult outpatients diagnosed with epilepsy at the Goiânia Municipal Psychiatry Clinic (Brazil) were collected and analyzed using high-performance liquid chromatography. The analytes and internal standard (zolpidem) were extracted by liquid-liquid extraction. A reversed phase column (ACE 5, C18, 150 x 4.6 mm i.d.) was used. The mobile phase was composed of acetonitrile (30%) and citric acid/phosphate buffer, pH 5.0 (70%). The gradient flow rate was from 0.7 to 1.2 mL/min and the detection wavelength was set at 210 nm for all analytes. The analysis revealed a linear range from 0.5 to 20.0μg/mL for carbamazepine/lamotrigine and 2.0 to 64.0 μg/mL for phenytoin/phenobarbital. Mean recovery ranged from 96.8% to 108.5% for carbamazepine/lamotrigine and 93.8% to 108.8% for phenytoin/phenobarbital. The quantification limit, precision (CV < 15%) and accuracy (A >85%) proved to be in accordance with the requirements stipulated by the Brazilian National Health Surveillance Agency (ANVISA). Nine outpatients were evaluated to confirm the validity of the method.

Análisis cuantitativo de la 3-hidroxi, 3-etil-, 3-fenil propionamida en plasma por cromatografía de líquidos de alta resolución / Quantitatyve analysis of 3-hydroxi, 3-ethyl, 3-phenyl propionomide in plasma by high resolution liquid cromatography

Se describe un método sensible y específico de cromatografía de alta resolución (HPCL) para el análisis en plasma humano de 3-hidroxi, 3-etil, 3-fenil propionami-da (HEPP), un nuevo anticonvulsivante. El estándar interno (2-hidroxi, 2-etil, 2-fenil acetamida HEPA) y la HEPP se extrajeron en acetonitrilo de plasma amortiguado, la extracción fue cercana al 100 por ciento respecto a la cantidad extraída de cada fármaco de solución salina amortiguada. El método consiste en HPCL en fase reversa (Lichro Spher 100 RP-18 en Lichro Cart 125-4), la fase móvil está compuesta de metanol-acetonitrilo-amortiguador de fosfatos (35/15/50 por vol) y detección ultravioleta a 200 nm. Las curvas de calibración fueron lineales y repetibles (coeficiente de correlación > 0.999). Las determinaciones de HEPP en plasma humano o en solución salina fueron lineales en el intervalo 0 - 10 µg/ml y el coeficiente de variación fue menor que 10 por ciento. HEPP es muy estable a temperatura ambiente y a 4 ºC, y puede ser cuantificada en presencia de otros antiepilépticos tales como: difenilhidantoina, clonazepam. carbamezepina y hexobarbital