Therefore, insulin conjugates with covalent or non-covalent cargos, such as AD or other CNS drugs, could potentially contribute to a promising strategy to cure CNS-related diseases. Nonetheless, intranasally administered insulin was delivered into the brain. Related to the real trajectory, intranasal labeled-insulins demonstrated distribution into the brain not only along the olfactory nerve but also the trigeminal nerve. Several ongoing AD clinical trials investigate the use of intranasal insulin delivery. Recently, it has been revealed that insulin improved Alzheimer’s disease (AD)-related dementia. Nose-to-brain drug delivery could solve the BBB-related repulsion problem. The nasal cavity directly leads from the olfactory epithelium to the brain through the cribriform plate of the skull bone. Thus, alternative approaches must be developed. ![]() However, the blood–brain barrier (BBB) prevents drugs from penetrating the capillary endothelial cells, blocking their entry into the brain. The direct delivery of central nervous system (CNS) drugs into the brain after administration is an ideal concept due to its effectiveness and non-toxicity.
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