title: Sustained steroid release in pulmonary inflammation model.
abstract: 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.
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
authors.forename: Harry
authors.initials: H
authors.lastname: Karmouty-Quintana
authors.forename: Faleh
authors.initials: F
authors.lastname: Tamimi
authors.forename: Toby K
authors.initials: TK
authors.lastname: McGovern
authors.forename: Liam M
authors.initials: LM
authors.lastname: Grover
authors.forename: James G
authors.initials: JG
authors.lastname: Martin
authors.forename: Jake E
authors.initials: JE
authors.lastname: Barralet
mesh_terms: 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
chemical_list: D000305:Adrenal Cortex Hormones