Novel PLGA Microspheres for Sustained Delivery of Antisense Oligonucleotide

Novel poly（lactide-co-glycolide acid）（PLGA） microspheres were developed for sustained delivery of antisense oligonucleotide（ASO）. First, a new cationic agent, polyethylenimine（PEI） conjugated to linoleic acid（LA）（PEI-LA） was synthesized by reacting PEI（Mw=800） with linoleoyl chloride. Then, PEI-LA was combined with LOR-2501 to form electrostatic complexes at moderate nitrogen-to-phosphate（N/P） molar ratios which were then encapsulated into poly（lactide-co-glycolide） microspheres by a multiple emulsion-solvent evaporation technique. With an increase in ASO/PEI-LA concentration from 5% to 10%, encapsulation efficiency of ASO in the micro- spheres reduced from 72.14% to 57.62%, and the particle size ofmicrospheres increased from 28.58 μm to 34.76 μm. In vitro studies show that the release profile of ASO from microspheres prepared at 7.5% ASO-PEI-LA lasted for 14 d The novel microspheres have a potential use as a sustained release vehicle for ASO.