Controlled release of oligonucleotide/polyethyleneimine complexes from PLGA-based microspheres: potential of spray-drying technique

In this work, the potential of spray-drying technique in the production of poly(lactide-co-glycolide) (PLGA) microspheres for the delivery of oligonucleotide/polyethylenimine (ODN/PEI) complexes was assessed. PLGA microspheres, entrapping the oligodeoxythymidilate pdT16 in association with PEI at nitrogen to phosphate ratios (N/P) 15 and 40, were prepared by spray-drying different emulsions. Microparticles obtained from a w/o emulsion at 1:5 volume ratio were collapsed and displayed a mean diameter in the range of 8.3 to 10.6 μm. A decrease in the aqueous phase volume (1:100 w/o ratio) yielded to regular microspheres with a smaller mean diameter. The co-encapsulation of PEI affected microsphere surface charge, which was strongly positive and depended on the amount of PEI entrapped. The release profiles of pdT16/PEI were affected by PLGA employed and PEI amount co-encapsulated. Microspheres releasing pdT16/PEI complexes at constant and optimal N/P ratios were selected for in vitro studies on HeLa cells. After 24 h of incubation, small-size positively-charged microspheres were effectively internalized into cells and, depending on the formulation, pdT16 could be located into the nucleus.