Transport of polymeric nanoparticle gene carriers in gastric mucus.
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.
Dawson
Michelle
M
Department of Chemical and Biomolecular Engineering, Biomedical Engineering, and Materials Science and Engineering, The Johns Hopkins University, Baltimore, Maryland, USA.
Krauland
Eric
E
Wirtz
Denis
D
Hanes
Justin
J
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
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