title: Rheological Properties of Cystic Fibrosis Bronchial Secretion and in Vitro Drug Permeation Study: The Effect of Sodium Bicarbonate.
abstract: Cystic fibrosis (CF) is characterized by a thick, sticky mucus responsible for both airway obstruction and resistance to drug diffusion, reducing the effectiveness of drug delivery to the lung. Studies of drug-mucus interaction may be a crucial step in therapeutic management of CF. In the present research, the effect of a saline solution of sodium bicarbonate (100 mM) on sputum viscosity and the permeation properties of ketoprofen lysinate (Klys) from a previously developed dry powder inhaler were evaluated.
  
  
  
  Rheological measurements were performed using an ARES rotational rheometer (Rheometrics, Inc.) with a parallel plate geometry. The gel fraction, separated from the liquid phase of various sputum samples from CF patients was loaded onto the plate. The elastic (G') and the viscous (G") moduli, tan δ (ratio of G" to G') and η* (complex viscosity) were evaluated as frequency-dependent parameters. Drug permeation across CF sputum from dry powders was studied by means of Franz-type vertical diffusion cells. The experiments were conducted on untreated sputum and on sputum treated with bicarbonate.
  
  
  
  Rheological studies showed that the elastic modulus (G') was always greater than the viscous modulus (G") and the viscosity decreased with increasing frequency, as for pseudo-plastic fluids. Bicarbonate caused a downward shift of both the elastic and viscous moduli, with a reduction in complex viscosity. As to drug permeation, the untreated sputum slowed down drug dissolution and permeation compared to buffer permeability (control). Permeation studies across CF sputum treated with bicarbonate showed higher Klys dissolution/permeation than untreated sputum.
  
  
  
  The interesting results confirm the previously reported bicarbonate. effectiveness in CF; this weak base seems to act by decreasing high viscosity of the CF bronchial secretion and, potentially, resulting in better mucus clearance and in fighting pulmonary infections.
authors.affiliation: 1 Department of Pharmacy, University of Salerno , Salerno, Italy .
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Stigliani
authors.affiliation: 1 Department of Pharmacy, University of Salerno , Salerno, Italy .
authors.forename: Michele Dario
authors.initials: MD
authors.lastname: Manniello
authors.affiliation: 2 U.O.C. Genetica Medica Giannina Gaslini Institute , Genoa, Genoa, Italy .
authors.forename: Olga
authors.initials: O
authors.lastname: Zegarra-Moran
authors.affiliation: 2 U.O.C. Genetica Medica Giannina Gaslini Institute , Genoa, Genoa, Italy .
authors.forename: Luis
authors.initials: L
authors.lastname: Galietta
authors.affiliation: 2 U.O.C. Genetica Medica Giannina Gaslini Institute , Genoa, Genoa, Italy .
authors.forename: Laura
authors.initials: L
authors.lastname: Minicucci
authors.affiliation: 2 U.O.C. Genetica Medica Giannina Gaslini Institute , Genoa, Genoa, Italy .
authors.forename: Rosaria
authors.initials: R
authors.lastname: Casciaro
authors.affiliation: 3 Department of Industrial Engineering, University of Salerno , Salerno, Italy .
authors.forename: Emilia
authors.initials: E
authors.lastname: Garofalo
authors.affiliation: 3 Department of Industrial Engineering, University of Salerno , Salerno, Italy .
authors.forename: Loredana
authors.initials: L
authors.lastname: Incarnato
authors.affiliation: 1 Department of Pharmacy, University of Salerno , Salerno, Italy .
authors.forename: Rita P
authors.initials: RP
authors.lastname: Aquino
authors.affiliation: 1 Department of Pharmacy, University of Salerno , Salerno, Italy .
authors.forename: Pasquale
authors.initials: P
authors.lastname: Del Gaudio
authors.affiliation: 1 Department of Pharmacy, University of Salerno , Salerno, Italy .
authors.forename: Paola
authors.initials: P
authors.lastname: Russo
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000503:physiopathology*; D058995:Dry Powder Inhalers; D055119:Elastic Modulus; D005260:Female; D006801:Humans; D007660:Ketoprofen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010539:Permeability; D012212:Rheology; D017693:Sodium Bicarbonate / Q000494:pharmacology*; D013183:Sputum / Q000187:drug effects* / Q000378:metabolism; D014783:Viscosity; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C029946:ketoprofen lysine; D017693:Sodium Bicarbonate; D007660:Ketoprofen; D008239:Lysine
keywords: cystic fibrosis; drug permeation; ketoprofen; rheology; sodium bicarbonate