Caracterização do efeito protetor e de encapsulamento de sistemas microtecnológicos de insulina oral baseados em Eudragit®

Abstract

Diabetes mellitus is a chronic, multifactorial, and multicausal disease that affects millions of people worldwide. Some research estimates that by 2045, the diabetic population could rise to 783 million, consequently increasing the use of insulin therapy. Classically, diabetes is classified into three types: Type 1 DM, Type 2 DM, and Gestational DM. However, it is now understood that this classification has become simplistic for defining Diabetes mellitus. But the core issue is the systemic hyperglycemia, which causes problems ranging from moderate to extremely severe, and can even lead to the patient's death. This metabolic disease not only impacts the patient's health but also significantly influences the economic sector, both in terms of treatment costs and the relationship of the affected person with the job market. Complications from diabetes can lead to premature death of patients, especially before the age of 60, causing a major impact on the workforce. It is a disease that moves billions of dollars in research for new treatments. The hormone that controls hyperglycemia is insulin. This uncontrolled hyperglycemia causes ingested carbohydrates to damage the human body. This hormone interacts with specific plasma membrane receptors, controlling glucose uptake, and is extremely important in various anabolic processes, energy storage, and inhibition of catabolic processes. Insulin therapy used in the treatment of DM is not very well accepted by patients due to the discomfort of its administration, with current treatments being exclusively daily subcutaneous injections or intravenous administration in hospital and emergency settings. Besides adherence to insulin treatment, determining the correct dosages is not very easy due to rebound hypoglycemia. This rebound hypoglycemia can cause: cardiovascular problems, cardiac arrhythmias, loss of consciousness, coma, and death. Due to these problems, the pharmaceutical industry, with the advancement of technologies, especially the advent of micro and nanoparticles, has researchers around the world investing in studies to transform parenteral insulins into oral insulins. The use of micro and nanoparticles helps not only with protection but also improves the targeting and release of insulin at the desired site, optimizing its therapeutic effect, improving its dosage regimen, administration method, and patient adherence. Polymethacrylate polymers are an excellent option for the development of these oral insulin microparticles. They are non-toxic substances with well-established properties by the FDA, being biocompatible with human physiology. These polymers can be biodegradable or not, and are also used in the food industry. They can be used for sustained and/or programmed release, as well as for protective coatings of the drug, in this case, insulin. Therefore, this work aims to fabricate three types of oral insulin microparticles, using three types of commercially available Eudragit® polymers: L100, S100, and RS30D. It also aims to characterize the protection and coating of these formulations through analytical tests such as FTIR (Fourier Transform Infrared Spectroscopy); Zeta Potential; Polydispersity; and morphological analysis by field emission gun scanning electron microscopy. Each Eudragit® reacted differently with insulin: L100 and S100 via hydrogen bonds, and RS30D in a more electrostatic manner, highlighting the difference in interaction with the drug and signaling possible differences in release. With these preliminary analyses, the formulation of Eudragit® L100 + Regular Insulin proved to be the most promising for a more elaborate formulation and future testing.