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Published on: April 6, 2017
Systemic and pulmonary effects of fluticasone administered through a metered-dose inhaler in rats
Ronald L Sorkness1, Jennifer L Remus, Louis A Rosenthal
1Morris Institute for Respiratory Research and the School of Pharmacy, University of Wisconsin, 777 Highland Avenue, Madison, WI 53705, USA. rlsorkne@wisc.edu
Background:
Metered-dose inhalers (MDIs) are convenient, simple, inexpensive, and reproducible devices for administering aerosolized drugs through the pulmonary route, but methods have not been available for use of these devices in small animals.
Objective:
We sought to test the efficacy of delivery of fluticasone through an MDI to rats with a rodent-adapted spacer chamber and to compare this treatment with systemic dexamethasone for the acute pulmonary allergic inflammatory response.
Methods:
Changes in body and thymus weights were used as indicators for systemic steroid effects. Rats were sensitized to ragweed pollen extract 2 weeks before the experiment, and pulmonary allergic responses were evaluated 48 hours after a single aerosolized antigen challenge on the basis of bronchoalveolar leukocytes, lung tissue sections, total lung capacity, and forced expiratory volumes.
Results:
Inhaled fluticasone caused dose-related systemic effects, indicating successful pulmonary drug delivery. Inhaled fluticasone was more effective than placebo but less effective than systemic dexamethasone in attenuating the increase in lung eosinophils and inflammatory infiltrates and the decrease in total lung capacity associated with the allergic inflammatory response. Inhaled fluticasone prevented airway obstruction and proximal inflammation, as did dexamethasone, but it appeared to have less effect in areas of lung served by the most distal airways.
Conclusion:
This is an effective method for use of MDIs to deliver inhaled drugs to small laboratory animals, and it should be valuable for investigations of treatment effects, as well as for in vivo testing of delivery devices.
Insights
A new method effectively delivers inhaled drugs to small animals using metered-dose inhalers (MDIs). This technique shows promise for studying pulmonary allergic responses and testing new drug delivery devices in vivo.
Area of Science:
- Pharmacology
- Respiratory Medicine
- Animal Models
Background:
- Metered-dose inhalers (MDIs) offer convenient pulmonary drug delivery but lack established methods for small animal use.
- Pulmonary drug delivery is crucial for treating respiratory conditions.
Purpose of the Study:
- To evaluate the efficacy of fluticasone delivered via MDI in rats.
- To compare MDI fluticasone with systemic dexamethasone for acute allergic lung inflammation.
Main Methods:
- Rats sensitized to ragweed pollen received aerosolized antigen challenge.
- Pulmonary allergic responses assessed via bronchoalveolar leukocytes, lung histology, lung capacity, and expiratory volumes.
- Systemic steroid effects monitored by body and thymus weight changes.
Main Results:
- Inhaled fluticasone demonstrated dose-related systemic effects, confirming pulmonary delivery.
- Fluticasone via MDI was more effective than placebo but less effective than systemic dexamethasone in reducing lung inflammation and improving lung capacity.
- MDI fluticasone, like dexamethasone, prevented airway obstruction and proximal inflammation, with lesser effects in distal airways.
Conclusions:
- An effective method for MDI drug delivery to small animals was established.
- This technique is valuable for investigating therapeutic effects and in vivo testing of delivery devices.
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