Nasal epithelium barrier

This refers to the transport across the epithelial cells, which can occur by passive diffusion, carrier-mediated transport, and/or endocytic processes (e.g., transcytosis). Traditionally, the transcellular route of nasal mucosa has been simply viewed as primarily crossing the lipoidal barrier, in which the absorption of a drug is determined by the magnitude of its partition coefficient and molecular size. However, several investigators have reported the lack of linear correlation between penetrant lipophilicity and permeability [9], which implies that cell membranes of nasal epithelium cannot be regarded as a simple lipoidal barrier. Recently, compounds whose transport could not be fully explained by passive simple diffusion have been investigated to test if they could be utilized as specific substrates for various transporters which have been identified in the... 

In the respiratory tract, mucus is also involved in the process of mucociliary clearance, which contributes to the epithelial barrier properties by entrapping potentially hazardous substances, such as dust and microorganisms, within a viscoelastic mucus blanket. The mucus is then propelled by the claw-like tips of hair-like cilia towards the throat (movement occurs in a downwards direction from the nasal epithelium, or... 

One method by which mucus protects the nasal epithelium is by acting as a physical barrier and respiratory mucus has been reported to retard the diffusion of water and a range of //-lactam antibiotics used to treat respiratory infections. The use of mucolytics, which alter the viscoelasticity of mucus, has been shown to increase the absorption of intranasally administered human growth hormone (hGH, M. Wt.=22 kDa). However, other studies have shown that antibodies (150-970 kDa) are able to diffuse through cervical mucus relatively unimpeded these latter studies tend to suggest that the diffusion barrier presented by mucus in the nasal cavity would be insignificant. 

The purpose of this chapter is to present overviews of a selection of the major endothelial and epithelial barriers to drug delivery for which there are either primary culture or cell line systems that recapitulate the characteristics of the in vivo barrier. Our objective is to define some general characteristics of cell culture models and highlight the more commonly applied primary cell cultures and cell lines in use today. Specifically, we focus on cell culture models for the intestinal epithelium, blood-brain barrier, pulmonary and nasal epithelium, ocular epithelium, placental barrier, and renal epithelium. Renal epithelium was included here primarily because some cell lines derived from this tissue [e.g., Madin-Darby canine kidney cells (MDCK)] are often used as surrogates for other barriers by pharmaceutical scientists. We have arbitrarily chosen to exclude the skin and liver from the scope of this overview. However, it should be noted that hepatocyte cell culture models, for example, are becoming more widely available and have been the subject of recent reviews.1,2... 

Local host defenses of both the upper and lower respiratory tract, along with the anatomy of the airways, are important in preventing infection. Upper respiratory defenses include the mucodliary apparatus of the nasopharynx, nasal hair, normal bacterial flora, IgA antibodies, and complement. Local host defenses of the lower respiratory tract include cough, mucodliary apparatus of the trachea and bronchi, antibodies (IgA, IgM, and IgG), complement, and alveolar macrophages. Mucus lines the cells of the respiratory tract, forming a protective barrier for the cells. This minimizes the ability of organisms to attach to the cells and initiate the infectious process. The squamous epithelial cells of the upper respiratory tract are not ciliated, but those of the columnar epithelium of the lower tract are. The cilia beat in a uniform fashion upward, moving particles up and out of the lower respiratory tract. 

Proteolysis. Proteolysis is the cleavage of amide bonds that comprise the backbone of proteins and peptides. The reaction can occur spontaneously in aqueous medium under acidic, neutral, or basic conditions. This process is accelerated by proteases, ubiquitous enzymes that catalyze peptide-bond hydrolysis at rates much higher than occur spontaneously. In humans, these enzymes only recognize sequences of L-amino acids but not d-amino acids. They are found in barrier tissues (nasal membranes, stomach and intestinal linings, vaginal and respiratory mucosa, ocular epithelium), blood, all internal solid organs, connective tissue, and fat. The same protease may be present in multiple sites in the body. 

Drags administered orally must cross the GI tract epithelium to be absorbed and enter the systemic circulation. Similarly, drags administered by alternative routes, such as the buccal, sublingual, nasal, pulmonary and vaginal routes, must all cross the appropriate epithelial interfaces to reach the general circulation. The types of epithelial interfaces, the barriers they pose to drag absorption, and the routes and mechanisms of drag absorption across these interfaces, are described below. 

NASAL AND PULMONARY EPITHELIUM 7.5.1. The Respiratory Airway Epithelial Barrier... 

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