Recent progress in polymeric non-invasive insulin delivery.

The design of carriers for insulin delivery has recently attracted major research attentions in the biomedical field. In general, the release of drug from polymers is driven via a variety of polymers. Several mechanisms such as matrix release, leaching of drug, swelling, and diffusion are usually adopted for the release of drug through polymers. Insulin is one of the most predominant therapeutic drugs for the treatment of both diabetes mellitus; type-I (insulin-dependent) and type II (insulin-independent). Currently, insulin is administered subcutaneously, which makes the patient feel discomfort, pain, hyperinsulinemia, allergic responses, lipodystrophy surrounding the injection area, and occurrence of miscarried glycemic control. Therefore, significant research interest has been focused on designing and developing new insulin delivery technologies to control blood glucose levels and time, which can enhance the patient compliance simultaneously through alternative routes as non-invasive insulin delivery. The aim of this review is to emphasize various non-invasive insulin delivery mechanisms including oral, transdermal, rectal, vaginal, ocular, and nasal. In addition, this review highlights different smart stimuli-responsive insulin delivery systems including glucose, pH, enzymes, near-infrared, ultrasound, magnetic and electric fields, and the application of various polymers as insulin carriers. Finally, the advantages, limitations, and the effect of each non-invasive route on insulin delivery are discussed in detail.