title: Formation and characterization of pDNA-loaded alginate microspheres for oral administration in mice.
abstract: Alginate, a natural polysaccharide, was explored in this study as an oral delivery vehicle of a mammalian expression vector into the murine intestinal mucosa. Alginate microspheres were produced through water-in-oil (W/O) emulsification method. Average diameter sizes of microspheres were 46.88 μm±3.07 μm with significant size reduction upon utilization of 1.0% Span80. Plasmid DNA (pDNA) carrying green fluorescent protein reporter gene (GFP), pVAX-GFP, was encapsulated within microspheres at efficiencies of 72.9 to 74.4%, carrying maximum load of 6 μg pDNA. Alginate microspheres demonstrated shrinkage in pH 1.2 and swelling in pH 9.0 with pDNA release about twice the amount released in acidic environment. Oral delivery of pVAX-GFP loaded-microspheres, at 50 μg, 100 μg and 150 μg dose, was performed on BALB/c mice. Tissue biodistribution, investigated through flow cytometric analysis, demonstrated GFP positive intestinal cells (<1.0%) with 1.3-fold higher levels for the 100 μg dose; therefore suggesting feasibility of the approach for oral gene delivery and vaccination.
authors.affiliation: Medical Genetics Laboratory, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
authors.forename: Nadine
authors.initials: N
authors.lastname: Nograles
authors.forename: Syahril
authors.initials: S
authors.lastname: Abdullah
authors.forename: Mariana Nor
authors.initials: MN
authors.lastname: Shamsudin
authors.forename: Nashiru
authors.initials: N
authors.lastname: Billa
authors.forename: Rozita
authors.initials: R
authors.lastname: Rosli
mesh_terms: D000284:Administration, Oral; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D004247:DNA / Q000008:administration & dosage*; D018014:Gene Transfer Techniques; D020723:Glucuronic Acid / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D006603:Hexuronic Acids / Q000737:chemistry; D051379:Mice; D008863:Microspheres; D010316:Particle Size; D010957:Plasmids / Q000235:genetics; D014018:Tissue Distribution
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D049452:Green Fluorescent Proteins; D020723:Glucuronic Acid; D004247:DNA