Influência da insulina oral no epitélio intestinal: uma avaliação dos efeitos da administração de nanopartículas poliméricas contendo insulina em animais alimentados com dieta hipercalórica

Abstract

Insulin is the most used and effective hormone in the control of Diabetes Mellitus (DM). Its application, however, is limited to the subcutaneous route. As it is an invasive route, it is associated with a series of disadvantages, leading to complications, resulting in low adherence to the treatment. The oral route is safer, due to its non-invasive character and prolonged therapeutic effect, but drugs administered by this route must have properties that guarantee their bioavailability. Among these factors, adequate solubility, stability in different environments in the gastrointestinal tract, in addition to intestinal permeability. Insulin, being a peptide hormone, if ingested, would immediately be cleaved by stomach enzymes, losing its function. Furthermore, its high molecular weight and the presence of surface charges make intestinal permeability to insulin another issue to be overcome. In order to increase the bioavailability of insulin by the oral route, oral insulin nanoparticles (INOR) were developed from Humulin® Regular insulin (IHR) and the polymer Eudragit® S100 (ES-100) by the spray-drying method. The INORs that were obtained had yield values greater than 99%. Quantification was performed by Ultra High Performance Liquid Chromatography (UHPLC). The method was specific and linear (R=0.999), with an analysis time of 3.0 minutes. To evaluate the effects of the INOR on the intestinal epithelium, the study was carried out in 60 Wistar rats divided into 4 Groups: Group 1 (Control), Group 2 (Diabetized), Group 3 (treated with INOR) and Group 4 (Diabetized treated with INOR). All groups received high-fat diet (HFD). For the diabetization, Groups 2 and 4 received 20 mg/kg of streptozotocin (STZ). The animals were weighed every fortnight, for 60 days. After this period and after euthanasia, samples were collected to perform the biochemical tests. During the 8 weeks, in the 4 groups, there was mild hyperglycemia and a slight increase in mass, even in those undergoing STZ and INOR. Analyzing the sizes of the villi and crypts of the duodenum, there was a statistical difference in Group 3, rats treated with INOR, showing an increase in the size of the crypt in relation to the other groups. The INORs had as a local effect the increase in the depth of the intestinal crypt, and action at the level of mesenteric and retroperitoneal fats even in animals subjected to HFD, managing to sensitize the lipid metabolism by visceral fats.