Sustained steroid release in pulmonary inflammation model.
There is a need for particles which exhibit controlled release of therapeutic agents delivered via the inhalational route, for tissue specific applications such as anti-cancer, bronchodilators and antiviral agents as well as drugs for systemic action. The aim of this study was to assess the acute toxicity, distribution and capacity of the microspheres to exhibit controlled release properties in an in vivo model of airway inflammation. Calcium pyrophosphate nanofibrous microspheres were loaded with dexamethasone phosphate (Dex-P); the profile of drug release was studied in vitro and validated in vivo. Unloaded microspheres were administered intra-tracheally (i.t.) to rats to assess the tissue reaction. The anti-inflammatory properties of the Dex-P loaded microspheres against an inflammatory agent (compound 48/80), were evaluated in vivo. Unloaded microspheres did not cause an inflammatory response when given at doses below 3mg, and appeared to be eliminated through mucus clearance mechanisms. Microspheres loaded with Dex-P but not Dex-P alone, were capable of inhibiting eosinophil and total inflammatory cell increases in bronchoalveolar lavage fluid for 42 h following a single application. These observations demonstrated that calcium pyrophosphate nanofibrous microspheres displayed in vivo controlled release properties, were well tolerated and did not accumulate in the lung.
Karmouty-Quintana
Harry
H
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Tamimi
Faleh
F
McGovern
Toby K
TK
Grover
Liam M
LM
Martin
James G
JG
Barralet
Jake E
JE
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D008854:Microscopy, Electron; D008863:Microspheres; D011014:Pneumonia / Q000188:drug therapy*; D051381:Rats
D000305:Adrenal Cortex Hormones