title: Influence of particle size and antacid on release and stability of plasmid DNA from uniform PLGA microspheres.
abstract: PLGA microspheres are attractive DNA delivery vehicles due to their controlled release capabilities. One major problem with PLGA microspheres is that they develop an acidic microclimate as the polymer degrades, lowering the intraparticle pH, and potentially damaging the DNA. Antacids have recently shown promise in buffering this acidic microclimate and enhancing protein stability. We manufactured uniform plasmid DNA-encapsulating PLGA microspheres of two sizes (47, 80 microm diameter) and antacid concentrations (0, 3% Mg(OH)2). Microspheres with antacid had a homogeneous surface coverage of small pores, which resulted in a significant reduction of the burst effect. The 47 microm microspheres exhibited complete release of plasmid DNA over the course of two months. Incomplete release was observed from 80 microm spheres, though microspheres with 3% Mg(OH)2 showed a higher cumulative release, suggesting that the antacid at least partially aids in increasing the stability of DNA. SEM was used to visualize the surface pore evolution and cross-sectional microsphere structure over time. Subsequent image analysis was used to quantify the increase of surface pore sizes. Cross-sectional images showed increasing internal degradation and erosion, which resulted in a hollowing-out of microspheres. Our studies show that the incorporation of antacid into the microsphere structure has potential in addressing some of the major problems associated with DNA encapsulation and release in PLGA microspheres.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois, 600 S. Mathews Ave, Urbana, IL 61801 USA.
authors.forename: Neelesh K
authors.initials: NK
authors.lastname: Varde
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Pack
mesh_terms: D000863:Antacids / Q000737:chemistry*; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000138:chemical synthesis*; D004247:DNA / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D019344:Lactic Acid / Q000008:administration & dosage / Q000138:chemical synthesis*; D008276:Magnesium Hydroxide / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009690:Nucleic Acid Conformation; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage / Q000138:chemical synthesis*; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000138:chemical synthesis*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis*; D016062:Porosity; D013499:Surface Properties
chemical_list: D000863:Antacids; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004247:DNA; D008276:Magnesium Hydroxide