Postdeposition dispersion of aerosol medications using surfactant carriers.
Inhaled aerosol drugs provide a means of directly treating the lungs; however, aerosol deposition and drug distribution can be nonuniform, especially in obstructive lung disease. We hypothesize that surfactant-based aerosol carriers will disperse medications over airway surfaces after deposition through surface tension driven flows, increasing dose uniformity and improving drug distribution into underventilated regions. We considered saline and surfactant aerosol delivery via cannula onto several model airway surfaces including porcine gastric mucus (PGM) and both cystic fibrosis (CF) and non-CF human bronchial epithelial cells (HBEs). Fluorescent dye and microspheres (d = 100 nm, 1 mum) were used to qualitatively and quantitatively assess postdeposition dispersion. Aerosol volume median diameters were in the 1-4 mum range. The tested surfactants included sodium dodecyl sulfate (SDS), cetyl trimethyl ammonium bromide (CTAB), tyloxapol, and calfactant. All surfactants tested on PGM (tyloxapol, calfactant, SDS, and CTAB) significantly increased dispersion area versus saline with all markers (2-20-fold increases; all p < 0.04). Both surfactants tested on CF HBEs (tyloxapol and calfactant) significantly increased dispersion area versus saline with all markers (1.6-4.1-fold increases; all p </= 0.02). Tyloxapol and calfactant were tested versus saline on non-CF HBE's as well. Calfactant significantly increased dispersion area with all markers (1.6-2.3-fold increases; all p </= 0.02), and tyloxapol significantly increased dispersion area with two of three markers (1.3, 1.9-fold increases; p = 0.03, 0.003). Surfactant carriers enhanced dispersion after aerosol deposition onto model airway surfaces, and may improve the efficacy of inhaled preparations such as inhaled antibiotics for cystic fibrosis.
Marcinkowski
Amy L
AL
Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Garoff
Stephen
S
Tilton
Robert D
RD
Pilewski
Joseph M
JM
Corcoran
Timothy E
TE
D000336:Aerosols; D000818:Animals; D001688:Biological Products / Q000737:chemistry; D002478:Cells, Cultured; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000737:chemistry; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D004847:Epithelial Cells / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D011092:Polyethylene Glycols / Q000737:chemistry; D011663:Pulmonary Surfactants / Q000737:chemistry*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry*; D013552:Swine; D014018:Tissue Distribution
D000336:Aerosols; D001688:Biological Products; D002593:Cetrimonium Compounds; D004337:Drug Carriers; D011663:Pulmonary Surfactants; D013501:Surface-Active Agents; D012967:Sodium Dodecyl Sulfate; D011092:Polyethylene Glycols; C117342:calfactant; C016811:tyloxapol; D000077286:Cetrimonium