Simvastatin delivery via inhalation attenuates airway inflammation in a murine model of asthma
| Autor: | Lan Xu, Jun-xia Jiang, Liang-liang Shen, Rui Cao, Qiang-min Xie, Fenfen Li, Hong-Yi Yao, Xing-wei Dong, Hui-juan Shen, Yun Sun |
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| Rok vydání: | 2012 |
| Předmět: |
Simvastatin
Ovalbumin medicine.medical_treatment Immunology Intraperitoneal injection Anti-Inflammatory Agents Cell Count Pharmacology Mice Pharmacokinetics Administration Inhalation Animals Immunology and Allergy Medicine RNA Messenger Adverse effect Mice Inbred BALB C Inhalation biology business.industry nutritional and metabolic diseases respiratory system Asthma Disease Models Animal Pharmacodynamics Drug delivery biology.protein Cytokines Female lipids (amino acids peptides and proteins) Bronchial Hyperreactivity Hydroxymethylglutaryl-CoA Reductase Inhibitors business Bronchoalveolar Lavage Fluid medicine.drug |
| Zdroj: | International Immunopharmacology. 12:556-564 |
| ISSN: | 1567-5769 |
| DOI: | 10.1016/j.intimp.2012.01.012 |
| Popis: | The dose-response of the pleiotropic effects of statins on airway inflammation has not yet been established and may differ from that of their cholesterol-lowering effects. High oral doses of statins may have adverse effects, and it may be possible to overcome the side effects and low clinical efficacy by administering statins via inhalation. In this study, we hypothesize that simvastatin is a potential anti-inflammatory drug with biological and pharmacokinetic properties suitable for delivery by the inhaled route. Mice were immunized with ovalbumin (OVA) and then challenged with aerosol OVA. Simvastatin was locally delivered by inhalation (i.h.) and intratracheal injection (i.t.) or systematically delivered by intraperitoneal injection (i.p.) and gavage (i.g.) during the OVA challenge. In a mouse model of asthma, i.h. simvastatin significantly and dose-dependently attenuated airway inflammation, remodeling and hyperresponsiveness in a RhoA-dependent pathway. Upon comparing the pharmacodynamics, i.h. simvastatin had a more potent effect than that of i.g. and i.p. simvastatin, and the i.h. or i.t. delivery routes led to a higher drug concentration in local lung tissue and a lower drug concentration in the plasma than that obtained by the i.g. These results suggest that simvastatin is a potential anti-inflammatory drug for airway inflammatory diseases with properties suitable for delivery by inhalation, which will probably reduce the side effects and increase clinical efficacy. |
| Databáze: | OpenAIRE |
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