ABSTRACT
Nasal delivery offers significant advantages over other noninvasive routes. These include ease of self-administration, accurate dosing, a highly vascularized mucosa leading to rapid absorption, and high systemic bioavailability. This delivery route offers a much lower enzyme activity relative to the oral mucosa and also avoids the first-pass metabolism associated with the oral route. The extent of macromolecular drug delivery across the nasal mucosa is inversely proportional to the molecular weight. Therefore, in order to increase nasal bioavailability, new approaches have been developed, which include penetration enhancers and the development of prodrugs, analogues, and particulate systems composed of biodegradable polymers. Absorption through the nasal mucosa is primarily dependent on the molecular size and hydrophobicity of the molecules [3, 4]. Low molecular weight hydrophilic molecules permeate readily through the porous aqueous channels of the endothelial basement membrane of the nasal epithelium. However, highly polar macromolecules encounter high resistance in passing through these channels. Therefore, new approaches should be investigated to enhance nasal permeability of polar, high molecular weight therapeutic agents, particularly for proteins and vaccines intended to elicit a systemic response. Nasal epithelial cells also express various transporters and receptors for macromolecular entry. Moreover, macromolecules as well as particulate polymeric nano-and microparticles can penetrate the epithelial cell layer by phagocytosis, micropinocytosis, and endocytosis by receptor-mediated or nonreceptor-mediated vesicular pathways. Viral vectors such as adeno-associated virus (AAV), cytomegalovirus (CMV), herpes simplex virus (HSV), and retrovirus (RV) could be engineered to deliver genes and other
macromolecules across the nasal epithelial cells. Liposomes and nanoparticles can be surface decorated with the outer protein coat of the virus to enhance cellular entry. 3.2.1 Nasal Anatomy
The nose provides the sense of smell and also functions to filter, humidify, entrap, and clear particles larger than 10 µm in size. The outer part of the nose is composed of bones and cartilage (Fig. 3.1A). The nasal cavity is separated into left and right passages by a nasal septum and is formed by cranial bones, the nasal bone, the ethmoid bone, and the vomer bone. These bones branch into highly folded segments called turbinates, which project along the lateral walls of the nasal passages. These interwined structures enhance the contact surface area between the inhaled air and the nasal epithelium and
Fig3.1
Fig3.2
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Fig3.2
Figure 3.1 (A) The anatomy of the nose. (B) The nasal mucosa.
