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The development of new oral insulin delivery systems could bring significant benefits to insulin-dependent patients due to the simplicity of the method, avoidance of pain caused by parenteral administration and maintenance of optimal therapeutic levels for a longer period. However, administration of such therapeutic proteins orally remains a challenge because insulin (Ins) is a very sensitive molecule and can be easily degraded under the existing pH conditions in the stomach and intestines. Moreover, due to the large size of insulin, intestinal epithelium permeability is very low. This could be improved by immobilizing insulin in the mesoporous silica pores (MSN), acting as a shield to protect the molecule integrity from the proteolytic degradation existing in the stomach and upper part of the small intestine. Due to the high adsorption capacity of insulin, biocompatibility, ease of functionalization with various organic and/or inorganic groups, high mechanical and chemical resistance, adjustable pore size and volume, MSN is considered an ideal candidate for the development of controlled release systems that are sensitive to various stimuli (pH, temperature) as well as to glucose. Modifying MSN surfaces by coating with various mucoadhesive polymers (chitosan, alginate, etc.) will also facilitate interaction with the intestinal mucus and improve intestinal retention time. Moreover, the development of glucose-responsive systems for achieving MSN-based self-regulated insulin delivery, decorated with various components serving as sensors – glucose oxidase (GODx) and phenylboronic acid (PBA) that can control the insulin dosage, avoiding overdose leading to serious hypoglycemia. MSN have also been tested for application as biosensors for glucose monitoring.