Revealing the Regional Localization and Differential Lung Retention of Inhaled Compounds by Mass Spectrometry Imaging.
J Aerosol Med Pulm Drug Deliv
; 33(1): 43-53, 2020 02.
Article
in En
| MEDLINE
| ID: mdl-31364961
ABSTRACT
Background:
For the treatment of respiratory disease, inhaled drug delivery aims to provide direct access to pharmacological target sites while minimizing systemic exposure. Despite this long-held tenet of inhaled therapeutic advantage, there are limited data of regional drug localization in the lungs after inhalation. The aim of this study was to investigate the distribution and retention of different chemotypes typifying available inhaled drugs [slowly dissolving neutral fluticasone propionate (FP) and soluble bases salmeterol and salbutamol] using mass spectrometry imaging (MSI).Methods:
Salmeterol, salbutamol, and FP were simultaneously delivered by inhaled nebulization to rats. In the same animals, salmeterol-d3, salbutamol-d3, and FP-d3 were delivered by intravenous (IV) injection. Samples of lung tissue were obtained at 2- and 30-minute postdosing, and high-resolution MSI was used to study drug distribution and retention.Results:
IV delivery resulted in homogeneous lung distribution for all molecules. In comparison, while inhalation also gave rise to drug presence in the entire lung, there were regional chemotype-dependent areas of higher abundance. At the 30-minute time point, inhaled salmeterol and salbutamol were preferentially retained in bronchiolar tissue, whereas FP was retained in all regions of the lungs.Conclusion:
This study clearly demonstrates that inhaled small molecule chemotypes are differentially distributed in lung tissue after inhalation, and that high-resolution MSI can be applied to study these retention patterns.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Albuterol
/
Salmeterol Xinafoate
/
Fluticasone
/
Lung
Limits:
Animals
Language:
En
Journal:
J Aerosol Med Pulm Drug Deliv
Journal subject:
TERAPIA POR MEDICAMENTOS
Year:
2020
Document type:
Article
Affiliation country: