Novel PLGA microspheres for sustained delivery of antisense oligonucleotide

Abstract

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(M _w=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 microspheres reduced from 72.14% to 57.62%, and the particle size of microspheres 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.

Keywords

Drug delivery / PLGA microsphere / Polyethylenimine / Antisense oligonucleotide

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