Encapsulation of plasmid DNA in biodegradable poly(D,L-lactic-co-glycolic acid) microspheres as a novel approach for immunogene delivery

A plasmid DNA encoding bacterial beta-galactosidase gene was encapsulated i n poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres. Plasmid DNA extrac ted from PLGA microspheres retained both structural and functional integrit y as evidenced by its restriction endonuclease digestion pattern and its ab ility to transfect COS-1 cells in vitro. PLGA microspheres protected plasmi d DNA from digestion by deoxyribonuclease I(DNase I) in vitro. The encapsul ation efficiency of plasmid DNA and its release rate depended on the molecu lar mass of PLGA. Lastly, J-774A macrophages phagocytosed PLGA microspheres loaded with plasmid DNA. Go-encapsulated monophosphoryl lipid A increased the rate of phagocytosis. These results suggest that biodegradable PLGA mic rospheres can deliver intact and functional plasmid DNA at controlled rates . Thus, PLGA microspheres may be used to jointly deliver genes and other bi ologically active molecules, e.g., immunomodulators, to antigen presenting cells. (C) 1999 Elsevier Science B.V. All rights reserved.