Biomaterials-Enhanced Intranasal Delivery of Drugs as a Direct Route for Brain Targeting

Abstract

Intranasal (IN) drug delivery is a non-invasive and effective route for the administration of drugs to the brain at pharmacologically relevant concentrations, bypassing the blood–brain barrier (BBB) and minimizing adverse side effects. IN drug delivery can be particularly promising for the treatment of neurodegenerative diseases. The drug delivery mechanism involves the initial drug penetration through the nasal epithelial barrier, followed by drug diffusion in the perivascular or perineural spaces along the olfactory or trigeminal nerves, and final extracellular diffusion throughout the brain. A part of the drug may be lost by drainage through the lymphatic system, while a part may even enter the systemic circulation and reach the brain by crossing the BBB. Alternatively, drugs can be directly transported to the brain by axons of the olfactory nerve. To improve the effectiveness of drug delivery to the brain by the IN route, various types of nanocarriers and hydrogels and their combinations have been proposed. This review paper analyzes the main biomaterials-based strategies to enhance IN drug delivery to the brain, outlining unsolved challenges and proposing ways to address them.

Research progress in brain-targeted nasal drug delivery

“…Powder-based formulations tend to result in stronger and more prolonged contact with the mucosa than solution-based formulations, leading to higher concentration gradients on both sides of the mucosa, thereby increasing drug absorption and brain bioavailability. Many other new dosage forms, such as gel or microsphere preparations, emulsions, liposomes, nanoparticles, and micelles are also conducive to improving the nasal absorption of drugs ( Marcello and Chiono, 2023 ). In summary, an appropriate dosage form should be selected based on the aforementioned specifications on a case-by-case basis depending on the properties of the drug being administered.…”

Intranasal Drug Delivery by Nanotechnology: Advances in and Challenges for Alzheimer’s Disease Management

“…The olfactory neuronal pathway encompasses intra- and extra-neuronal mechanisms [ 166 ], spanning the olfactory epithelium, olfactory bulb, and lamina propria. Administered drugs reach the olfactory bulb from the olfactory region through a transcellular mechanism [ 167 ].…”

“…Therefore, a pressing need exists for a delivery system that can effectively traverse central nervous system barriers and guide the active ingredient to its intended target site without disrupting the physiology and structure of the nasal epithelium or the blood–brain barrier. Nanocarrier-based drug delivery systems present a promising alternative to traditional intranasal delivery methods [ 166 , 184 , 185 ]. Polymers, metal- and lipid-based particulate systems, vesicular carriers, and miscellaneous carriers such as nanoemulsions, nanosponges, dendrimers, and quantum dots are extensively explored nanocarrier-based platforms for intranasal drug delivery in the context of Alzheimer’s disease.…”

The improving strategies and applications of nanotechnology-based drugs in hepatocellular carcinoma treatment

“…Targeting of a drug refers to the characteristic that a drug is selectively concentrated in the target organ, target tissue, or target cell ( Fang et al, 2023 ; Marcello and Chiono, 2023 ). The target location can be divided into three categories, that is, the first level refers to the specific target tissue or organ, the second level refers to the specific target cell, and the third level refers to the specific targets in the cell.…”