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 in poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres. Plasmid DNA extracted from PLGA microspheres retained both structural and functional integrity as evidenced by its restriction endonuclease digestion pattern and its ability to transfect COS-1 cells in vitro. PLGA microspheres protected plasmid DNA from digestion by deoxyribonuclease I (DNase I) in vitro. The encapsulation efficiency of plasmid DNA and its release rate depended on the molecular mass of PLGA. Lastly, J-774A macrophages phagocytosed PLGA microspheres loaded with plasmid DNA. Co-encapsulated monophosphoryl lipid A increased the rate of phagocytosis. These results suggest that biodegradable PLGA microspheres can deliver intact and functional plasmid DNA at controlled rates. Thus, PLGA microspheres may be used to jointly deliver genes and other biologically active molecules, e.g., immunomodulators, to antigen presenting cells.