title: Transport of polymeric nanoparticle gene carriers in gastric mucus.
abstract: Nanoparticle transport through mucosal barriers is often restricted owing to mucoadhesion and the highly viscoelastic nature of mucus gels, which may limit efficient drug and gene delivery. We formulated sub-200 nm particulates from poly(d,l-lactic-co-glycolic) acid (PLGA) and the cationic surfactant dimethyldioctadecylammonium bromide (DDAB). Subsequently, anionic DNA was condensed to the surface to obtain gene carriers with transfection rates 50-fold higher than those of naked DNA in vitro. Using the method of multiple particle tracking (MPT), we measured the transport rates of dozens of individual PLGA-DDAB/DNA nanoparticles in real time in reconstituted pig gastric mucus (PGM) that possessed physiologically relevant rheological properties. The average transport rate of PLGA-DDAB/DNA nanoparticles was 10-fold higher than those of similar size polystyrene nanoparticles. Improved transport rates, stability in mucus, and ability to transfect cells make PLGA-DDAB/DNA nanoparticles candidates for mucosal DNA vaccines and gene therapy.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Biomedical Engineering, and Materials Science and Engineering, The Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Dawson
authors.forename: Eric
authors.initials: E
authors.lastname: Krauland
authors.forename: Denis
authors.initials: D
authors.lastname: Wirtz
authors.forename: Justin
authors.initials: J
authors.lastname: Hanes
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D004548:Elasticity; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D018014:Gene Transfer Techniques; D019344:Lactic Acid / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D014018:Tissue Distribution; D014783:Viscosity
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D011108:Polymers; D000644:Quaternary Ammonium Compounds; C046112:didodecyldimethylammonium; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004247:DNA