The Dilemma of Insulin Delivery into the Brain: A Comprehensive Review.

Insulin is a peptide hormone that is essential for regulating body homeostasis. Furthermore, it is involved in various neurological functions such as memory, behaviors, and cognition. The ubiquitous distribution of insulin receptors on various brain cells, such as neurons, microglia, astrocytes, and oligodendrocytes, and their differential localization across various brain regions, including the hippocampus, hypothalamus, and olfactory bulb, collectively underscore the crucial involvement of insulin in the modulation of cerebral functions. Along with ageing, in some pathological conditions such as diabetes and brain insulin resistance, the need for exogenous insulin is felt to compensate for insulin deficiency. In these cases, the biggest obstacle to the delivery of insulin to the brain is the blood-brain barrier (a physical barrier consisting of endothelial cells with tight junctions), which prevents the direct entry of most substances possessing high molecular weight, like insulin, into the brain. Therefore, different delivery methods have been proposed by researchers for insulin delivery that directly or indirectly cause the transfer of insulin to the brain. Some of these methods lack high efficiency and cause many side effects for the patient. In this regard, many new technologies have come to the aid of researchers and have introduced more effective delivery strategies, including the use of nanocarriers. Despite the promising outcomes demonstrated in the experimental models, the utilization of these techniques in human studies remains at a nascent stage and necessitates further comprehensive investigation. This review article aims to examine the diverse methods of insulin administration to the brain by gathering extensive information on insulin and its obstacles to brain delivery.