RESUMEN
To our knowledge, no such polymeric nanoparticle formulation toxicity study has been reported for oral use. The oral route of drug administration is generally preferred because of its versatility, safety and relative patient comfort. Hence, there is an outstanding need of research for polymeric nanoparticles to find whether they are stable for prolonged shelf life, and yet have no toxicity when administered orally. The main objective of this study is to assess the safety of Glipizide (GZ) loaded polymeric nanoparticle systematically and to observe the toxic effects of nanoparticles on the functions of various tissues and organs in rats. The rats were randomly divided into 7 groups (6 in each group); viz. one normal control group (received saline), two groups (1:2 and 1:5 ratio of GZ-Chitosan nanoparticle), two groups (1:2 and 1:5 ratio of GZ-Poly(methyl methacrylate) nanoparticle) and two groups (1:2 and 1:5 ratio of GZ-Ethyl Cellulose nanoparticle). After 30 days of nanoparticle administration, the blood haematology and biochemistry were investigated, along with the histopathological examination. The rats did not show any significant changes in all the parameters studied and the results clearly evidenced its safety. All formulations showed in vitro haemolytic activity less than 5%. Conclusion drawn from the present study is that the polymeric nanoparticles may be a suitable device for safe oral administration. A rigorous safety of these nanoparticles would enable their use in the field of diabetic therapy.
Asunto(s)
Glipizida/administración & dosificación , Glipizida/toxicidad , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/toxicidad , Nanocápsulas/química , Administración Oral , Animales , Celulosa/análogos & derivados , Celulosa/química , Quitosano/química , Femenino , Hemólisis/efectos de los fármacos , Microscopía Electrónica de Rastreo , Nanocápsulas/administración & dosificación , Nanocápsulas/ultraestructura , Nanotecnología , Tamaño de la Partícula , Polimetil Metacrilato/química , Ratas , Ratas WistarRESUMEN
1. The interference of cholestyramine and activated charcoal with the absorption of glipizide was studied. 2. In a cross-over study comprising three phases, single doses of cholestyramine (8 g), activated charcoal (8 g) or water only were given to six healthy volunteers together with a single dose of glipizide. 3. The absorption of glipizide was moderately (29%, P less than 0.01) reduced by cholestyramine and greatly reduced (81%, P less than 0.01) by activated charcoal. 4. If cholestyramine and glipizide are used concomitantly, glipizide should be taken 1-2 h beforehand. In acute glipizide overdosage, activated charcoal can be used to reduce absorption.