RESUMEN
This study determined whether meloxicam in nanocapsules modifies stomach and liver damage caused by free meloxicam in mice. Male Swiss mice were treated with blank nanocapsules or meloxicam in nanocapsules or free meloxicam (10 mg/kg, intragastrically, daily for five days). On the seventh day, blood was collected to determine biochemical markers (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, total bilirubin, unconjugated bilirubin, albumin and alkaline phosphatase). Stomachs and livers were removed for histological analysis. There was no significant difference in the biochemical markers in the plasma of mice. Meloxicam in nanocapsules did not have an ulcerogenic potential in the stomach or cause lipid peroxidation in the stomach and liver. Free meloxicam increased the ulcerogenic potential in the stomach and lipid peroxidation in the stomach and liver. Meloxicam in nanocapsules caused less histological changes than free meloxicam. In conclusion, polymeric nanocapsules can represent a technological alternative to reduce the toxicity caused by meloxicam.
Asunto(s)
Caproatos/farmacología , Lactonas/farmacología , Hígado/efectos de los fármacos , Nanocápsulas/química , Polisorbatos/farmacología , Estómago/efectos de los fármacos , Tiazinas/antagonistas & inhibidores , Tiazoles/antagonistas & inhibidores , Animales , Peso Corporal/efectos de los fármacos , Caproatos/administración & dosificación , Caproatos/química , Relación Dosis-Respuesta a Droga , Mucosa Gástrica/metabolismo , Lactonas/administración & dosificación , Lactonas/química , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Meloxicam , Ratones , Nanocápsulas/administración & dosificación , Tamaño de los Órganos/efectos de los fármacos , Polisorbatos/administración & dosificación , Polisorbatos/química , Estómago/patología , Relación Estructura-Actividad , Tiazinas/administración & dosificación , Tiazinas/toxicidad , Tiazoles/administración & dosificación , Tiazoles/toxicidadRESUMEN
AIMS: The development of new treatments for inflammation and pain continues to be of high interest, since long-acting effect is critical for patients. The present study investigated whether the polymeric nanocapsules, a drug delivery system, have pharmacological effect on acute nociceptive and inflammatory models in mice. MAIN METHODS: Swiss mice (20-25 g) were previously pre-treated with meloxicam-loaded nanocapsules (M-NC) or free meloxicam (M-F) or suspension without drug (B-NC), at a dose of 5 mg/kg (per oral) at different times (0.5-120 h). Antinociceptive and antiedematogenic effects were evaluated by chemical (acetic acid-induced abdominal writhing, nociception and paw edema induced by formalin and glutamate, croton oil-induced ear edema) and thermal (tail immersion and hot-plate) tests. KEY FINDINGS: M-NC reduced the licking time- and paw edema-induced by glutamate and formalin, while M-F did not have an effect. In the acetic acid-induced abdominal writhing and croton oil-induced ear edema, analysis of time-course revealed that M-NC showed a response more prolonged than M-F. In the hot-plate test, a thermal test, the time-course analysis indicated a similar increase in the latency response to thermal stimuli of M-NC and M-F, while in the tail-immersion test M-F had an effect at 0.5 h and M-NC at 24 h. SIGNIFICANCE: Polymeric nanoparticles had antinociceptive, anti-inflammatory and antiedematogenic effects in the formalin and glutamate tests, and prolonged the effect in acetic acid and croton oil tests, but not in thermal tests, supporting the idea that the inflammatory process in tissues facilitates the vectoring of polymeric nanoparticles.