Intratracheal Instillation Methods and the Distribution of Administered Material in the Lung of the Rat

Abstract

Intratracheal instillation is widely used for respiratory toxicity tests in experimental animals. However, there are wide variations in the techniques used for instillation, and it is thus difficult to compare the results obtained using different techniques. To examine the effect of instillation methods, we compared the distribution of a test substance in the lungs of rats after intratracheal instillations under various conditions. Rats received an intratracheal instillation of 0.3 mL of india ink suspension under different conditions as follows: 3 different angles of body restraint, 0° (supine horizontal), 45° (supine head up) and 90° (vertical head up); 2 instillation speeds, high (40 mL/min) and low (4 mL/min); and 2 different devices, a standard bulb-tipped gavage needle and an aerosolizing microsprayer designed for intratracheal instillation. One hour after treatment under these various conditions, rats were sacrificed, and the local distribution of the suspension in the lungs was observed. No animal restrained in the supine head-up or vertical head-up position died from the treatment; however, fatalities were observed when rats were restrained in the supine horizontal position except under high-speed dosing conditions with a microsprayer. Better distribution of the suspension in the lungs was observed in the rats restrained in the supine head-up position after instillation at high speed when compared with other conditions. These results indicated that high-speed instillation to the subject restrained in the supine head-up position is an appropriate condition for performing intratracheal instillation.

Method for Pulmonary Administration Using Negative Pressure Generated by Inspiration in Mice

“…Furthermore, the evaluation using a dye showed that the negative pressure method can deliver a drug specifically to a lung, and uniformly within it ( Figure 3). This result is different from a previous report, in which a drug solution was distributed in both the lungs and the stomach using the positive pressure administration method [18]. In our method, the drug solution was administered when the oral sonde was inserted in the airway of a mouse, because this method mainly depends on inhalation by the mice, and not on positive pressure.…”

The Influence of Quercetin on Maternal Immunity, Oxidative Stress, and Inflammation in Mice with Exposure of Fine Particulate Matter during Gestation

“…Even though intratracheal instillation is used as an alternative method for studying inhalation exposure, the localization of the test material in the lungs from inhalation and intratracheal instillation differs [23], which may affect the results. In addition, further studies are needed to explore the mechanism of lymphocyte changes under PM exposure.…”

Challenges Associated with the Pulmonary Delivery of Therapeutic Dry Powders for Preclinical Testing

“…Nose-only administration delivered significantly fewer particles to the lung than intratracheal instillation and the deposited particles were cleared much more efficiently from the lung within 6-and 24-hour observational timepoints than particles delivered by intratracheal delivery. Further, small operational changes within a delivery technique using a particular delivery device can change the lung distribution patterns within the animal (Foster et al, 2001;Wong, 2007;Hasegawa-Baba et al, 2014). Hasegawa-Baba and colleagues showed a significant difference in pulmonary distribution patterns generated by intratracheal instillation depending on the angle at which the animal was intubated, the speed at which the drug was aerosolized into the lungs, and the volume of the dose delivered (Hasegawa-Baba et al, 2014).…”

“…Further, small operational changes within a delivery technique using a particular delivery device can change the lung distribution patterns within the animal (Foster et al, 2001;Wong, 2007;Hasegawa-Baba et al, 2014). Hasegawa-Baba and colleagues showed a significant difference in pulmonary distribution patterns generated by intratracheal instillation depending on the angle at which the animal was intubated, the speed at which the drug was aerosolized into the lungs, and the volume of the dose delivered (Hasegawa-Baba et al, 2014). These differences in the operation of preclinical devices are inevitable based on individual operators working in different laboratories.…”