In vitro characterization and in vivo performance of mefenamic acid-sodium diethyldithiocarbamate based liposomes

Mefenamic acid (MFA) is a hydrophobic drug with low dissolution rate. This study aimed to develop stable and reproducible aqueous formulations of MFA using liposomes as drug carriers. The drug entrapment, particles size and drug release profiles, and stability and reproducibility of the liposomes were determined. In addition, the maximum tolerated dose (MTD) was determined in rats via the oral and intraperitoneal routes of administration. Also, the anti-inflammatory efficacy of these liposomes was evaluated using carrageenan-induced paw edema model in rats. MFA-DDC based liposomes demonstrated a drug entrapment efficacy of 93.6%, particles size of 170.9 nm, and polydispersity index of 0.24 which were not statistically affected when stored in room and refrigerated temperatures for at least 4 weeks. The MTD of the intraperitoneally administrated MFA-loaded liposomes was 20 mg MFA/kg, whereas for those of oral administrations, it was up to 80 mg MFA/kg. Intraperitoneal dose (80 mg MFA/kg) of MFA-DDC liposomes induced extrapyramidal symptoms associated with significant elevation in serum potassium and muscle enzymes. Moreover, significant inhibition of paw edema was demonstrated by the oral and intraperitoneal routes. These findings suggest that MFA-DDC based liposomes are an effective formulation of MFA and recommend the use of bioequivalence assessments with commercial formulations.

Morphometric alterations induced by the toxicity of variable sizes of silver nanoparticles / Alteraciones morfométricas inducidas por la toxicidad de diferentes tamaños de nanopartículas de plata

Silver nanoprticles (SNPs) are invested in medical, industrial and environmental applications. Little if any, is known about the morphometric alterations induced by the toxicity of SNPs. The aim of the present work is to find out the effect of variable size of SNPs on different morphometric parameters. Adult healthy male mice (BAL/C) were subjected to (10 nm, 20 nm, 40 nm 60 nm and 100 nm) SNPs for 35 days. Silver NPs caused non-significant decline on the average weight, significant decline in food consumption, increase in water intake, unilateral blindness, tanning fur color and cholestasis together with a decrease in the relative ratio of the liver, kidney and spleen weight to body weight. Mice subjected to 10 nm and 20 nm were more affected than mice receiving larger nanoparticles. These findings may indicate that SNPs could induce morphometric alterations that are size related wheresmaller SNPs have more impact than the larger ones.

Poco se sabe acerca de las alteraciones morfométricas inducidas por la toxicidad de las nanopartículas de plata (NPP). El objetivo fue investigar el efecto del tamaño variable de las NPP en diferentes parámetros morfométricos. Ratones machos adultos sanos (BAL/C) fueron sometidos a diferentes NPP de diferentes tamaños durante 35 días (10 nm, 20 nm, 40 nm 60 nm y 100 nm, respectivamente). Las NPP causaron una disminución no significativa del peso promedio, una disminución significativa en el consumo de alimentos, un aumento de la ingesta de agua, ceguera unilateral, cambios en el color de piel y colestasis junto con una disminución en el tamaño promedio del hígado, riñón y el peso del bazo, en relación al peso corporal. Los ratones sometidos a 10 nm y 20 nm fueron más afectados que los ratones que recibieron las nanopartículas más grandes. Estos resultados pueden indicar que las NPP podrían inducir alteraciones morfométricas que están relacionadas con el tamaño, en las cuales las NPP más pequeñas tienen un mayor impacto que las más grandes.