Eudragit L-100 capsules/aromatize and quaternerize chitosan for insulin nanoparticle oral delivery on toxic oxidative stress in rat liver and kidney.

BACKGROUND Insulin, like most peptides, is classified as a hydrophilic and macromolecular drug that considered as a low permeable and un-stable compound in the gastrointestinal (GI) tract. The acidic condition of the stomach can degrade insulin molecules. Moreover, the presence of proteolytic activities of some enzymes such as trypsin and chymotrypsin can hydrolysis amide-bonds between various amino-acids in the structure of peptide and proteins. However, due to its simplicity and high patient compliance, oral administration is the most preferred route of systemic drug delivery and the for development of an oral delivery system some obstacles in oral administration of peptides and proteins including as low permeability and low stability of the proteins in GI should be overcome. OBJECTIVE In this study, the effects of orally insulin nanoparticles (INPs) prepared from quaternerized N-aryl derivatives of chitosan on the biochemical factors of the liver in diabetic rats were studied. METHODS INPs composed of methylated (amino benzyl) chitosan were prepared by the PEC method. Lyophilized INPs was filled in preclinical capsules and the capsules were enteric-coated with Eudragit L100. Twenty Male Wistar rats were randomly divided into four groups: group1: normal control rats, group 2: diabetic rats, group 3: diabetic rats received capsules INPs(30U/kg/day, orally), group 4: the diabetic rats received regular insulin (5U/kg/day, subcutaneously). At the end of the treatment time, serum, liver and kidney tissues were collected. Biochemical parameters in serum were measured using spectrophotometric methods. Also, oxidative stress was measured in plasma, liver and kidney. Histological studies were performed using H and E staining. RESULTS Biochemical parameters, liver and kidney injury markers in serum of the diabetic rats that received INPs improved significantly compared with diabetic group. INPs reduced oxidative toxic stress biomarkers in serum, liver and kidney of the diabetic treated group. Furthermore, a histopathological change was developed in the treated groups. CONCLUSION Capsulated INPs can prevent diabetic liver and oxidative kidney damages (similar regular insulin). Therefore oral administration of INPs seems that it is safe.