Formulation of poly(D,L-lactic-co-glycolic acid) microparticles for rapid plasmid DNA delivery

Abstract

An optimised water-in-oil-in-water double emulsion process for the microencapsulation of plasmid DNA in poly(D,L-lactic-co-glycolic acid) (PLGA) was used to prepare microparticles from a range of different PLGA formulations. This process has been developed using pharmaceutically accepted solvents and is potentially scaleable. Incorporation of plasmid DNA in the microparticles of up to 11 microg/mg was obtained and the retention of plasmid DNA integrity was considerably greater than previously reported. Microparticle structure was determined, by scanning electron microscopy, to be hollow and size distribution characteristics were found to be independent of polymer formulation. The ability to vary the plasmid DNA release profile by changing the PLGA formulation and polymer concentration used in the encapsulation process was also demonstrated. This ability to control the release profile of the microparticles was shown to be especially important as the physical integrity of the encapsulated plasmid DNA was found to deteriorate with extended release times in vitro.