Nasal instillation

Femandez-Urrusuno et al. (1999) investigated the potential of chitosan (MW <50,000-130,000 DD 70-87%) nanoparticles as a system for improving the systemic absorption of insulin following nasal instillation. Nanoparticles prepared by ionotropic gelation with tripolyphosphate... 

Nakamura et al. ° studied the adhesion of water-soluble and neutral polymers, hydroxypropyl cellulose (HPC), xanthan gum (XG), tamarind gum (TG), and polyvinyl alcohol (PVA) to nasal mucosa in vitro and in vivo. The polymers, mixed with a dye, were applied as powders to the nasal cavity of rabbits, and the remaining dye residue was determined at 2, 4, and 6 h after nasal instillation with a thin fiberscope. The polymer XG showed the longest residence time of the dye in the cavity, followed by TG, HPC, and PVA in decreasing order. For the mixture XG and XG-PVA (2 8), some residue of dye could still be observed 6h after administration. The order of adhesion of these polymers to agar plates in vitro agreed with that of their mucoadhesion in vivo. Ilium et al. introduced bioadhesive microspheres for nasal delivery of poorly absorbable drugs. Radiolabelled microspheres made from diethylaminoethyl (DEAE)-dextran, starch microspheres, and albumin microspheres were administered to human volunteers and appeared to be cleared significantly slower than solutions or... 

St. Clair MBG, Gross EA, Morgan KT. 1990. Pathology and cell proliferation induced by intra-nasal instillation of aldehydes in the rat Comparison of glutaraldehyde and formaldehyde. Toxicol Pathol 18 353-361. 

Nasal instillation of [ H]-benzo[a]pyrene (0.13 mg/kg) to hamsters resulted in the metabolism of [ H]-benzo[a]pyrene in the nasal cavity (Dahl et al. 1985). A large fraction of the metabolites was recovered from the epithelial surface, indicating that benzo[a]pyrene was first absorbed in the mucosa, metabolized, and returned to the mucus. Monkeys and dogs received nasal instillation of [ C]-benzo[a]pyrene at doses of 0.16-0.21 mg/kg (Petridou-Fischer et al. 1988). Radiolabeled metabolites were detected in the nasal cavity, but little or no activity was detected in the blood and excreta of either species during the 48 hours after exposure. These results indicate that absorption of benzo[a]pyrene and/or its metabolites was poor or very slow following nasal instillation in monkeys and dogs. 

Approximately 50% of the benzo[a]pyrene that was intratracheally instilled in hamsters was metabolized in the nose (Dahl et al. 1985). The metabolite produced in the hamster nose included tetrols, the 4,5-, 7,8-, and 9,10-dihydrodiol. quinones, and 3-and 9-hydroxybenzo[a]pyrene. Similar metabolites were detected in nasal and lung tissues of rats inhaling benzo[a]pyrene (Wolff et al. 1989b). The prevalence of quinone production was not seen in hamsters as it was in rats (Dahl et al. 1985 Weyand and Bevan 1987a, 1988). In monkeys and dogs, dihydrodiols, phenols, quinones, and tetrols were identified in the nasal mucus following nasal instillation of benzo[a]pyrene (Petridou-Fischer et al. 1988). in vitro metabolism of benzo[a]pyrene in the ethmoid turbinates of dogs resulted in a prevalence of phenols (Bond et al. 1988). However, small quantities of quinones and dihydrodiols were also identified. 

Petridou-Fischer J, Whaley SL, Dahl AR. 1988. In vivo metabolism of nasally instilled... 

Wang, J., Chen, C., Liu, Y, et al. 2008a. Potential neurological lesion after nasal instillation of Ti02 nanoparticles in the anatase and rutile crystal phases. Toxicology Letters 183(1-3), 72-80. 

In a double-blind, crossover, randomized trial in 10 healthy volunteers midazolam 0.2 mg/kg was given by nebulizer and liquid instillation nasally 5 days apart [30 ]. Plasma concentrations were greater after intranasal midazolam. Nasal instillation caused increased sedation but no difference in the time to sedation. There were no respiratory adverse events. Blood pressure and oxygen saturation fell in both groups (peak reduction at 15 minutes) but none required extra oxygen. Mean heart rate and diastolic pressure were increased. The incidence of unpleasant adverse effects was greater after intranasal midazolam, and nasal stinging, eye irritation, hiccups, and excessive secretions were common. One patient with asthma became wheezy after intranasal administration. 

Figure 11.10 The contents of copper in each tissue of mice 1 week postexposure to different sized copper particles by nasal instilled administration of 1 or 40mgkg body weight. Represents significant difference from the control group (Dunnett s P<0.05), represents significant difference from the L-Micro group (Student s P<0.05), + represents significant difference from the L-Nano group (Student s P<0.05). 2009 American Scientific Publishers.

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