Tailoring Formulations for Intranasal Nose-to-Brain Delivery: A Review on Architecture, Physico-Chemical Characteristics and Mucociliary Clearance of the Nasal Olfactory Mucosa

Abstract

The blood-brain barrier and the blood-cerebrospinal fluid barrier are major obstacles in central nervous system (CNS) drug delivery, since they block most molecules from entering the brain. Alternative drug delivery routes like intraparenchymal or intrathecal are invasive methods with a remaining risk of infections. In contrast, nose-to-brain delivery is a minimally invasive drug administration pathway, which bypasses the blood-brain barrier as the drug is directed from the nasal cavity to the brain. In particular, the skull base located at the roof of the nasal cavity is in close vicinity to the CNS. This area is covered with olfactory mucosa. To design and tailor suitable formulations for nose-to-brain drug delivery, the architecture, structure and physico-chemical characteristics of the mucosa are important criteria. Hence, here we review the state-of-the-art knowledge about the characteristics of the nasal and, in particular, the olfactory mucosa needed for a rational design of intranasal formulations and dosage forms. Also, the information is suitable for the development of systemic or local intranasal drug delivery as well as for intranasal vaccinations.

Pharmacotechnical Development of a Nasal Drug Delivery Composite Nanosystem Intended for Alzheimer’s Disease Treatment

“…Indeed, the olfactory pathway is mainly responsible for the translocation of negatively charged nanoparticles, whereas the positively charged nanoparticles reach the brain more slowly, by involving the trigeminal pathway [50]. Intranasally applied nanoparticles have to penetrate the mucus layer covering nasal mucosa to reach the olfactory mucosa, and thus the CNS [51]. Interactions between particles and mucus could lead to trapping and wrapping of nanoparticles in mucus, making them less suitable as efficient vehicles for nose-to-brain delivery [27].…”

Acrylated Eudragit® E PO as a novel polymeric excipient with enhanced mucoadhesive properties for application in nasal drug delivery

“…Drug delivery through mucosal routes of administration offers numerous advantages such as improved bioavailability of active pharmaceutical ingredients, ease of therapy application and in some cases the possibility of targeting particular organs (Andrews et al, 2009;Khutoryanskiy, 2011;Khutoryanskiy, 2014). In recent years, nasal administration has gained a lot of interest due to the possibility for bypassing the blood-brain barrier and targeting the brain directly through drug absorption via olfactory mucosa (Gänger et al, 2018;Pires et al, 2018;Battaglia et al, 2018;Sonvico et al, 2018). This minimally invasive route to deliver drugs directly to the brain could potentially offer new opportunities for treating various neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases (Poovaiah et al, 2018).…”

Niosome-Based Approach for In Situ Gene Delivery to Retina and Brain Cortex as Immune-Privileged Tissues

“…In any case, and despite the promising future that awaits gene therapy, some controversial issues still need to be improved. At the moment, all of the gene therapy treatments approved for human use by different regulatory authorities are based on viral vectors, which rises controversy regarding their safety profile, limited gene-packing capacity, large-scale production, and high costs [164]. Consequently, during the last years, research on non-viral vectors has gained "momentum" as a safer alternative to their viral vectors counterparts, and the number of clinical trials has considerably increased since 2010 (www.clinicaltrials.gov).…”