Estudo cientométrico e descritivo da evolução das estratégias biofarmacêuticas para administração oral da insulina

Abstract

The growing prevalence of obesity, associated with a sedentary lifestyle and modern eating habits, contributes to the increase in the number of individuals with Diabetes Mellitus. The application of insulin in patients with insulin-dependent diabetes is the main therapeutic treatment developed to resolve the problems arising from deficient endogenous insulin production, as it is the hormone responsible for promoting the reduction of blood glucose. Treatment for diabetic patients through parenteral insulin administration, despite helping to mitigate the problems arising from the disease, leads to several adverse effects from its application. Faced with the discomfort resulting from subcutaneous insulin injections, research has been carried out over the last few decades to propose approaches for developing new therapeutic strategies for its administration. Given this, the oral route has been the target of research for insulin administration, as it is practical and comfortable for diabetic patients. However, some obstacles, such as physical and chemical-enzymatic barriers in the gastrointestinal tract, related to absorption by the intestinal epithelium, must be overcome for the administered insulin to reach the circulation and exert its proper functions. Objective: In this sense, this work aimed to present a scientometric and descriptive review on the evolution of different biopharmaceutical strategies developed over the years to overcome the obstacles to oral insulin administration. Results and Discussion: The evolution of the development of these biopharmaceutical strategies was designed according to the concerns of each era in which between 1970 and 1990 the main obstacle included enzymatic degradation, in which approaches with polymers and enzyme inhibitors were developed. Subsequently, at the end of the 90s there was a growing concern about the instability of the insulin molecule, which led to the advancement of research into formulation approaches with chemical modifications of the protein, the use of acidity modifiers, surfactants and the use of molecules that promoted endocytosis mediated by membrane receptors. Finally, at the end of 2010, concern turned to the low diffusion and permeability of insulin, leading to the development of strategies such as the use of chelating agents and cell-penetrating peptides. In the current decade, 2020 to 2024, researchers, by combining these strategies discovered in previous decades, hope to significantly improve the effectiveness of oral insulin, offering a convenient and less invasive alternative to traditional subcutaneous administration. Conclusion: The reviewed research highlights a significant evolution in biopharmaceutical strategies for delivering oral insulin over the decades. From the 1970s to the present, efforts have focused on overcoming challenges such as enzymatic degradation, molecular instability, and low intestinal permeability. Innovations such as the use of polymers, enzyme inhibitors, chemical modifications to insulin, and cell-penetrating agents reflect continued adaptation to clinical and technological needs. Combining these approaches promises to improve the effectiveness of oral insulin, offering a more convenient and less invasive option for patients with diabetes, aligning with demands for more accessible and effective treatments.