Preliminary safety assessment of Eudragit® polymers nanoparticles administration in the rat brainMosaad A. Abdel-Wahhab, Olivier Joubert, Yasser A. Khadrawy, Ramia Safar, Aziza A. El-Nekeety, Carole Ronzani, Hussein G. Sawie, Nabila S. Hassan, Luc Ferrari, Bertrand H. Rihn.
Although nanotechnology can provide useful carriers to protect successfully active agents, it is necessary to determine the possible toxicity of these technological products before any extensive use. The aim of the current study was to evaluate the effects on the nervous system of Eudragit® polymers nanoparticles (EUD-Nps), considered as model of drug delivery carriers. Nile red-labeled EUD-NPs were prepared by a double emulsion/solvent evaporation technique. Male Sprague-Dawley rats were treated orally (PO) or intraperitoneally (IP) with a single dose of EUD-NPs (50 mg/kg bw). Animals were sacrificed after 4h, 48 h, 1 week and 3 weeks and the brain of each rat was removed and dissected into the forebrain, midbrain and hindbrain regions. Acetylcholinesterase (AChE) activity, lipid peroxidation, reduced glutathione and nitric oxide were determined in different brain region homogenate. Other samples were used for the histological and fluorescent examinations. The results indicated that within the two routes of administration, all the tested parameters showed insignificant changes during the tested intervals and all of them were in the normal range of the control by the 3rd week. Moreover, the histological examination revealed a normal histological picture of the brain tissues after 3 weeks of administration. The fluorescent examination showed that EUD-NPs were found in the brain tissues at all the studied times. These findings showed that EUD-NPs have the ability to cross the blood brain barrier but induced little toxic effects on the brain. Further studies will be needed to verify the fate of these NPs in the long term before using them as a vector.
Eudragit® polymers; nanoparticles; toxicity; brain; oxidative stress; acetylcholiesterase activity; Sprague-Dawley rats