Development and evaluation of an inhalation chamber for in vivo tests

ABSTRACT The bioavailability, toxicity, and therapeutic efficacy of a drug is directly related to its administration route. The pulmonary route can be accessed by inhalation after fumigation, vaporization or nebulization. Thus, pharmacological and toxicological evaluation accessed by an apparatus specifically designed and validated for this type of administration is extremely important. Based on pre-existing models, an inhalation chamber was developed. This presents a central structure with five animal holders. The nebulized air passes directly and continuously through these holders and subsequently to an outlet. Evaluation of its operation was performed using clove essential oil, a nebulizer, and a flow meter. The air within the chamber was collected by static headspace and analyzed by gas chromatography with a flame ionization detector. For this purpose, a 2.5 minutes chromatographic method was developed. The air flow in each of the five outputs was 0.92 liters per minute. During the first minute, the chamber became saturated with the nebulized material. Homogeneous and continuous operation of the chamber was observed without accumulation of volatile material inside it for 25 minutes. The inhalation chamber works satisfactorily for in vivo tests with medicines designed to be administrated by inhalation.

Effect of Nano-sized Carbon Black Particles on Lung and Circulatory System by Inhalation Exposure in Rats

OBJECTIVES: We sought to establish a novel method to generate nano-sized carbon black particles (nano-CBPs) with an average size smaller than 100 nm for examining the inhalation exposure risks of experimental rats. We also tested the effect of nano-CBPs on the pulmonary and circulatory systems. METHODS: We used chemical vapor deposition (CVD) without the addition of any additives to generate nano-CBPs with a particle size (electrical mobility diameter) of less than 100nm to examine the effects of inhalation exposure. Nano-CBPs were applied to a nose-only inhalation chamber system for studying the inhalation toxicity in rats. The effect on the lungs and circulatory system was determined according to the degree of inflammation as quantified by bronchoalveolar lavage fluid (BALF). The functional alteration of the hemostatic and vasomotor activities was measured by plasma coagulation, platelet activity, contraction and relaxation of blood vessels. RESULTS: Nano-CBPs were generated in the range of 83.3-87.9 nm. Rats were exposed for 4 hour/day, 5 days/week for 4 weeks to 4.2 x 10(6), 6.2 x 10(5), and 1.3 x 10(5) particles/cm3. Exposure of nano-CBPs by inhalation resulted in minimal pulmonary inflammation and did not appear to damage the lung tissue. In addition, there was no significant effect on blood functions, such as plasma coagulation and platelet aggregation, or on vasomotor function. CONCLUSION: We successfully generated nano-CBPs in the range of 83.3-87.9 nm at a maximum concentration of 4.2 x 10(6) particles/cm3 in a nose-only inhalation chamber system. This reliable method can be useful to investigate the biological and toxicological effects of inhalation exposure to nano-CBPs on experimental rats.