Encapsulation of oligonucleotide/polyethylenimine complexes in PLGA-based microspheres by spray-drying technique.

In our recent work poly(lactide-co-glycolide) (PLGA) microspheres able to deliver oligonucleotide/polyethylenimine (PEI) complexes were designed. A model oligonucleotide, namely the oligothymidilate pdT16, was encapsulated alone or in association with PEI at different nitrogen/phosphate ratios by the multiple emulsion-solvent evaporation technique. It was shown that the encapsulation of pdT16/PEI complexes into microspheres allowed both a reduction of the citotoxicity of the complex and an improvement of the intracellular penetration of pdT16. Moreover, when high PEI concentrations were used the oligonucleotide was preferentially located in the nucleus. Nevertheless, it was shown that the addition of PEI resulted also in larger and porous microparticles, which could account for a rapid oligonucleotide release profile. In order to obtain smaller and non-porous microparticles, which can be used for a wider range of applications (e.g. oral vaccination) in this work PLGA-based microspheres entrapping pdT16/PEI complexes were processed by the spray-drying technique. Moreover, an analytical method for the quantitative determination of PEI was set-up and used to measure its loading in and release from the microspheres. Thus, microspheres prepared from different PLGA types and at different pdT16/PEI ratios, were fully characterised for dimension, morphology, encapsulation efficiency and release kinetics of both pdT16 and PEI.