Comparison of process parameters for microencapsulation of plasmid DNA in poly(D,L-lactic-co-glycolic) acid microspheres.
Poly(D,L-lactic-co-glycolic) acid (PLGA) microspheres containing plasmid DNA encoding the firefly luciferase gene were prepared using the water-in-oil-in-water (w/o/w) double emulsion and solvent evaporation method. In this study, we investigated the effects of three process parameters on DNA microencapsulation: (1) emulsification method used to generate the primary emulsion, (2) water/oil ratio during formation of the first emulsion, and (3) surfactant concentration used in the preparation of the second emulsion. The resulting formulations were also analyzed for microsphere size, encapsulation efficiency, and kinetics of DNA release. We found that although each process alteration resulted in encapsulation of biologically active, structurally intact DNA, the surfactant and water/oil ratio significantly affected the size, release kinetics and encapsulation efficiency of plasmid DNA.
Hsu
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YY
Zycos, Inc., Cambridge, MA 02138, USA. shsu@zycos.com
Hao
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T
Hedley
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ML
D001672:Biocompatible Materials / Q000737:chemistry; D004247:DNA / Q000276:immunology / Q000378:metabolism*; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions; D019344:Lactic Acid / Q000737:chemistry*; D008156:Luciferases / Q000235:genetics; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D010957:Plasmids / Q000235:genetics*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013010:Sonication; D013501:Surface-Active Agents / Q000494:pharmacology*; D013997:Time Factors
D001672:Biocompatible Materials; D004655:Emulsions; D011108:Polymers; D013501:Surface-Active Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004247:DNA; D008156:Luciferases