title: A strategy to deliver genes to cystic fibrosis lungs: a battle with environment.
abstract: Cystic fibrosis (CF) sputum, a tenacious biopolymer network accumulating in the airways, critically interferes with the effectiveness of pulmonary gene delivery. To overcome this challenge, nanoparticulate ternary gene-polymer complexes were encapsulated in inhalable dry microparticles containing mannitol. When applied on a layer of artificial sputum, which comprised major components of CF sputum such as DNA and mucin, mannitol microparticles rapidly dissolved in it and enhanced transport of nanoparticles across the sputum layer. Despite the improvement of nanoparticle transport in the artificial sputum, the gene-polymer complex passing the sputum did not show gene transfection because of the significant inactivation by DNA and, to a lesser extent, mucin. Particle size measurement suggested that aggregation of the gene transfer agents was mainly responsible for the activity loss. These results indicate that the delivery of gene transfer agent across CF sputum depended not only on the ability to penetrate the sputum but also on preservation of the activity during and/or after the transport.
authors.affiliation: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
authors.forename: Basma M
authors.initials: BM
authors.lastname: Ibrahim
authors.forename: Seungman
authors.initials: S
authors.lastname: Park
authors.forename: Bumsoo
authors.initials: B
authors.lastname: Han
authors.forename: Yoon
authors.initials: Y
authors.lastname: Yeo
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D003432:Cross-Linking Reagents / Q000737:chemistry; D003550:Cystic Fibrosis / Q000235:genetics / Q000628:therapy*; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D018014:Gene Transfer Techniques; D006820:Hyaluronic Acid / Q000737:chemistry; D008168:Lung / Q000378:metabolism*; D008353:Mannitol / Q000737:chemistry*; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011094:Polyethyleneimine / Q000737:chemistry; D013183:Sputum / Q000378:metabolism; D014162:Transfection
chemical_list: D003432:Cross-Linking Reagents; D004337:Drug Carriers; D008353:Mannitol; D011094:Polyethyleneimine; D006820:Hyaluronic Acid; D004247:DNA