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.
Highlights
Drug delivery technologies such as liquid, semi-solid or particulate formulations are important to deliver pharmaceutical compounds safely to their desired site of therapeutic activity [1]
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
N2B is not limited to small molecule drugs, as peptides or proteins, even stem cells, viruses and nucleotides have already been proven to pass from the nose to the brain. [3,10,11]
Summary
Drug delivery technologies such as liquid, semi-solid or particulate formulations are important to deliver pharmaceutical compounds safely to their desired site of therapeutic activity [1]. A highly critical point in drug delivery is the low availability of drugs in the central nervous system (CNS) due to the blood-brain barrier. This barrier prevents 95% of molecules from entering the CNS by numerous tight junctions and efflux transporters [2]. A chronic drug supply can be provided by implanted medical devices Such techniques are in clinical use, these routes of administration are invasive and their use is predominantly limited to intensive care as the risk of infections is not neglectable [5,6,7,8,9]. A safe and efficient drug delivery platform technology for CNS active molecules is needed
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