Toxicological assessment of orally delivered nanoparticulate insulin

Subacute toxicological assessment on diabetic rats was conducted after 15 days of daily oral administration of nanoparticulate insulin. Haematological and biochemical analyses were conducted on blood and urine, biopsies performed on organs and tissues, and histology analysed by optical microscopy. Insulin-loaded nanoparticles alone did not change liver or kidney functions. The increase of some hepatic parameters was attributed to diabetes physiopathology and to chemical inducement of diabetes and not to the nanoparticle composition since diabetic controls showed the same variations. In terms of kidney function, parameters such as urea nitrogen and creatinine, were also similar to normal rats with the exception of glycosuria. This single effect was due to diabetes physiopathology and the method of induction, and not to the nanoparticle composition, since non-dosed diabetic rats showed the same alteration. Even so, glycosuria levels of animals dosed with insulin-loaded nanoparticles were lower than control diabetic rats which may indicate an effective hypoglycaemic response. Nanoparticles did not exhibit toxicity in haematological parameters. Finally, organ histology was similar between dosed animals and normal rats with the exception of pancreas histology.