Shortcut Approaches to Substance Delivery into the Brain Based on Intranasal Administration Using Nanodelivery Strategies for Insulin

Abstract

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. However, the blood–brain barrier (BBB) prevents drugs from penetrating the capillary endothelial cells, blocking their entry into the brain. Thus, alternative approaches must be developed. The nasal cavity directly leads from the olfactory epithelium to the brain through the cribriform plate of the skull bone. Nose-to-brain drug delivery could solve the BBB-related repulsion problem. Recently, it has been revealed that insulin improved Alzheimer’s disease (AD)-related dementia. Several ongoing AD clinical trials investigate the use of intranasal insulin delivery. Related to the real trajectory, intranasal labeled-insulins demonstrated distribution into the brain not only along the olfactory nerve but also the trigeminal nerve. Nonetheless, intranasally administered insulin was delivered into the brain. 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. In this review, I will introduce the CNS drug delivery approach into the brain using nanodelivery strategies for insulin through transcellular routes based on receptor-mediated transcytosis or through paracellular routes based on escaping the tight junction at the olfactory epithelium.

Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury

“…It is one of the main causes of the disturbances in learning and memory. The most effective way of insulin delivery to the brain is its intranasal administration, in which insulin enters directly to the brain, bypassing the blood-brain barrier [ 11 , 12 ]. In clinical trials, the intranasal administration of insulin to patients with Alzheimer’s and other neurodegenerative diseases was shown to improve the cognitive functions (see, for example, [ 15 , 16 , 17 , 18 , 19 ]).…”

“…One of the most promising ways to correct insulin deficiency in the brain is its intranasal administration, since in this case the hormone enters the brain directly with the participation of cells of the olfactory and trigeminal nerves, bypassing the blood-brain barrier [ 11 , 12 ]. The neuroprotective effect of intranasally administered insulin is supported by numerous studies on the prevention of neurodegenerative brain damage in experimental animals [ 1 , 13 , 14 ].…”

Spray Freeze Dried Lyospheres® for Nasal Administration of Insulin

“…More recent approaches intend to use nasal insulin in a different therapeutic context, which is the nose-to-brain delivery in cognitive impairment [39,40]. Although, in these studies, the focus was mainly on the permeation modifying components, such as nanocarrier-assisted delivery, rather than on the question of a liquid or a solid final dosage form, this also underlines the general benefit of a freeze-dried particle system for nasal drug delivery.…”

Delivery of Orally Administered Digestible Antibodies Using Nanoparticles

“…Drug delivery systems are highly important in solving barrier problems, such as transmembrane transportation in drug discovery and development. I have described a transporter-conscious drug design for crossing the cell membrane based on carrier-mediated transport [ 5 ], delivery of substances into cells across the membrane using cell-penetrating peptides through endocytosis or direct translocation [ 6 ], drug internalization into cancer cells that express specific proteins to avoid off-target side effects in cancer therapy [ 7 ], substance delivery into the brain across the blood–brain barrier (BBB) based on transcytosis [ 8 ], and intranasal conjugated substance delivery into the brain using insulin as a carrier [ 9 ]. Despite these approaches, problems in drug delivery persist.…”