In nasal epithelia

Zabner, J., Couture, L. A., Gregory, R. J., Graham, S. M., Smith, A. E. and Welsh, M. J. (1993). Adenovirus-mediated gene transfer transiently corrects the chloride transport defect in nasal epithelia of patients with cystic fibrosis. Cell 75, 207-216. 

Corticosteroids have also been examined for their effects on CBF. Interestingly, whilst corticosteroids exert effects that are ultimately protective and regenerative in the injured airway mucosa, there is evidence from studies in nasal epithelia that they actually reduce CBF (Stafenger, 1987). Whether this occurs in the pulmonary airways, and if so its potential significance, is not known. 

Hamman et al. [281,282] tested five trimethyl chitosans with different degrees of quaternization as nasal delivery systems the degree of quaternization had a major role in the absorption enhancement of this polymer across the nasal epithelia in a neutral environment. 

Quinton H.W., Grant W., Thrasivoulou C.Q. and Besser G.M. (1997). Gonadotropin-releasing hormone immunoreactivity in the nasal epithelia of adults with Kallmann s syndrome and isolated hypogonadotropic hypogonadism, in the early midtrimester human fetus. J Clin Endocrinol Metab 82, 309-314. 

NT265 Tesfaigzi, ]., J. Th ng, J. A. Hotchkiss, J. R. Harkema, and P. S. Wright. A small proline-rich protein, SPRRl, is upregulated early during tobacco smoke-induced squamous metaplasia in rat nasal epithelia. Am J Respir Cell Mol Biol 1996 14(5) 478-486. 

Locally irritating or sensitizing dmgs must be used with caution in this route. Nasal epithelia, and in particular the cilia, are highly sensitive and fragile. This contrasts with, for example, the buccal epithelium which is much more robust and less prone to irritation. The fragility of the tissue also means that this route is particularly sensitive to the adverse effects of penetration enhancers. Damage to the epithelium could result in compromised mucocilary clearance which is associated with respiratory disease. 

The distribution of propylene oxide within the body has been studied in experimental animals by means of measurement of its alkylation products (adducts) with DNA in various tissues and with hemoglobin in red blood cells. In rats, exposed to the compound by inhalation, the highest DNA adduct levels were found in the nasal epithelia, followed by lung, lymphocytes, spleen, liver, and testis. The adduct level in the respiratory mucosa... 

Bhalla DK, Mahavni V, Nguyen T, et al. 1991. Effects of acute exposure to formaldehyde on surface morphology of nasal epithelia in rats. J Toxicol Environ Health 33 171-188. 

Hamman, J. H., Stander, M., Kotze, A. F., Monti, D., Chetoni, P. J. (2002). Effect of degree of quaternization of N-trimethyl chitosan chloride on absorption enhancement In vivo evaluation in rat nasal epithelia,... 

Bhatnagar, K.P. Kallen F.C. 1975. Quantitative observations on the nasal epithelia and olfactory innervation in bats. Acta. Anat., 97 272-282. 

Hamman JH, Slander M, Kotze AF (2002) Effect of the degree of quatrmrisation of N-trimethyl chitosan chloride on absorption enhancemart in vivo evaluatirat in rat nasal epithelia. Int J Pharm 232 235-242... 

The nasal tissue is highly vascularized and provides efficient systemic absorption. Compared with oral or subcutaneous administration, nasal administration enhances bioavailability and improves safety and efficacy. Chitosan enhances the absorption of proteins and peptide drugs across nasal and intestinal epithelia. Gogev et al. demonstrated that the soluble formulation of glycol chitosan has potential usefulness as an intranasal adjuvant for recombinant viral vector vaccines in cattle [276]. 

Excised nasal mucosae obtained from various animal species are tools frequently used to study nasal transport and metabolism ([53], Chap. 4). Maintaining the viability of the excised nasal tissues during the experimental period is crucial. Most studies were performed with epithelia excised from rabbits, bovine, sheep, and dogs tissues [54-57], This excised nasal tissue model has been shown to be well suited for studies on nasal permeation and metabolism of drugs. However, species differences in the activity of various enzymes found in human versus these animal nasal mucosae have become an important issue. 

Answer Aerosol delivery of the CFTR gene. Both viruses and liposome-DNA complexes are capable of successful CFTR gene transfer to the nasal and airway epithelia of patients with CF. In fact, gene transfer to the airways is one of the few areas where liposome-DNA complexes match the expression obtained using viral vectors without the viruses inflammatory side effects. Current trials are aimed at optimizing gene delivery with reduced toxicity to produce sustained correction of the epithelial transport defect. 

---