Advances in pH-Sensitive Polymers for Smart Insulin Delivery.

Since diabetes mellitus has become one of the most serious threats to human health, researchers have been designing new drugs and developing new technologies to control the blood glucose level (BGL) while improving patient compliance. In addition to the traditional subcutaneous injection method, alternative routes of insulin delivery have been investigated and tested, including oral, pulmonary, transdermal, and nasal. The final goal of all these technologies is to develop a system that releases insulin in a controlled manner depending on the BGL. pH-Sensitive polymers appear to be good candidates to achieve this goal because they exhibit a conformational transition when the pH in the surrounding medium fluctuates, which changes the solubility of the polymers and leads to the swelling of hydrogels. Many pH-sensitive polymers, such as poly(2-dimethylamino)ethylmethacrylate) and natural biopolymers such as chitosan, have been used in different delivery systems. This review focuses on the most commonly used pH-sensitive polymers and their applications in insulin delivery systems. In particular, the relationship between the chemical structure of the polymeric systems and their insulin delivery performance is discussed.