Nasal route, drug delivery

The nasal route of delivery is not applicable to all drugs. Polar drugs and some macromolecules are not absorbed in sufficient concentration because of poor membrane permeability, rapid clearance, and enzymatic degradation into the nasal cavity. 

S. Gungor, A. Okyar, S. Erturk-Toker, G. Baktir, and Y. Ozsoy, Ondansetron-loaded chitosan microspheres for nasal antiemetic drug delivery An alternative approach to oral and parenteral routes. Drug Dev. Ind. Pharm., 36 (7), 806-813,2010. 

S. Mathison, R. Nagilla, and U. B. Kompella. Nasal route for direct delivery of solutes to the central nervous system Fact or fiction J Drug Target 5 415—441 (1998). 

In comparison to the skin, the buccal mucosa offers higher permeability and faster onset of drug delivery, whereas the key features which help it score over the other mucosal route, the nasal delivery system, include robustness, ease of use, and avoidance of drug metabolism and degradation. The buccal mucosa and the skin have similar structures with multiple cell layers at different degrees of maturation. The buccal mucosa, however, lacks the intercellular lamellar bilayer structure found in the stratum corneum, and hence is more permeable. An additional factor contributing to the enhanced permeability is the rich blood supply in the... 

The nasal route of drug delivery is used for the direct administration of medicines to the nose for treatment of local conditions or the systemic delivery of compounds that are not easily delivered by the oral route. It is also suggested that there may be a direct route for drug absorption to the central nervous system (CNS) from the olfactory region of the nose. 

The nasal route is generating increasing interest as a route for the administration of local treatments and a cost-effective and patient-friendly alternative to injection for systemic delivery [49]. The special advantages of nasal delivery make it attractive for (i) crisis treatment where rapid onset of action is desirable (e.g., pain, migraine, panic attacks), (ii) systemic delivery of compounds that at present can only be delivered by injection (peptides/pro-proteins/vaccination), and (iii) direct targeting of the CNS (polar drugs for the treatment of CNS disorders). 

The nasal route of drug delivery avoids the liver first-pass effect, but the pseudo-first-pass effect owing to nasal metabolism of drugs is still a concern. Many enzymes such as carboxylesterase, aldehyde dehydrogenase, glutathione transferases, UDP-glucoronyl transferase, epoxide hydrolases, CYP-dependent monoxygenases, exo- and endopeptidases and proteases are present in the nasal mucosa.106 108,110,116 CYP enzymes are present abundantly in the olfactory epithelium.107,110... 

The nonperoral mucosal delivery routes such as buccal, nasal, and vaginal sites offer barriers to drug molecules similar to that of the peroral route. Drugs delivered via these routes have to be small (<300 Da), lipophilic in nature, and with low dosage regimen requirements. The different approaches used to deliver drugs across these mucosae include the use of enzyme inhibitors, penetration enhancers, bioadhesive patches, prodrugs, liposomes, and solubility modifiers.96,106,130... 

Due to the lack of activity after oral administration for most peptides and proteins, administration by injection or infusion - that is, by intravenous (IV), subcutaneous (SC), or intramuscular (IM) administration - is frequently the preferred route of delivery for these drug products. In addition, other non-oral administration pathways have been utilized, including nasal, buccal, rectal, vaginal, transder-mal, ocular, or pulmonary drug delivery. Some of these delivery pathways will be discussed in the following sections in the order of the increasing biopharmaceutic challenges to obtain adequate systemic exposure. 

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