Evaluation of intranasal delivery route of drug administration for brain targeting

• Published in: Brain research bulletin Vol. 143; pp. 155 - 170
• Main Authors: Erdő, Franciska, Bors, Luca Anna, Farkas, Dániel, Bajza, Ágnes, Gizurarson, Sveinbjörn
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2018
• Subjects: CNS indication; Delivery enhancer techniques; Drug delivery; Intranasal administration; Transporter interactions; IFN-β1b; BBB; EPO; AUC; ANG II; RPMI 2650; l-DOPA; V1; V2; V3; Delivery enhancer techniques; AD; P-gp; FGF; PACAP; IN; FST; EN; IGF-1; Intranasal administration; NGF; OEC; LCC; IL-6; TST; CNS indication; ADNP; E; ONF; CNS; Drug delivery; SC; IF γ; MCP1; Transporter interactions; CSF; GA; MSC; MCAO; GLP-1; CaCo-2; MOG; SCA-1; VEGF; OSN; HIV; PD; scFv; TJ; TEER; TGF-β1; PK; HD; ALI; GALP
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2018.10.009

[Display omitted] •The two main pathways of intranasal drug absorption are the olfactory and trigeminal routes.•The intranasal drugs can bypass the blood-brain barrier and blood-CSF barrier.•There are in vitro, ex vivo and in vivo models for testing drug penetration by intranasal route.•The drug penetartion from nasal cavity can be enhanced by various formulations and devices.•Transporter modulation can also help in nasal delivery of their substrates. The acute or chronic drug treatments for different neurodegenerative and psychiatric disorders are challenging from several aspects. The low bioavailability and limited brain exposure of oral drugs, the rapid metabolism, elimination, the unwanted side effects and also the high dose to be added mean both inconvenience for the patients and high costs for the patients, their family and the society. The reason of low brain penetration of the compounds is that they have to overcome the blood-brain barrier which protects the brain against xenobiotics. Intranasal drug administration is one of the promising options to bypass blood-brain barrier, to reduce the systemic adverse effects of the drugs and to lower the doses to be administered. Furthermore, the drugs administered using nasal route have usually higher bioavailability, less side effects and result in higher brain exposure at similar dosage than the oral drugs. In this review the focus is on giving an overview on the anatomical and cellular structure of nasal cavity and absorption surface. It presents some possibilities to enhance the drug penetration through the nasal barrier and summarizes some in vitro, ex vivo and in vivo technologies to test the drug delivery across the nasal epithelium into the brain. Finally, the authors give a critical evaluation of the nasal route of administration showing its main advantages and limitations of this delivery route for CNS drug targeting.