Poly(lactide-co-glycolide) microspheres for the controlled release of oligonucleotide/polyethylenimine complexes

✍ Scribed by Giuseppe De Rosa; Fabiana Quaglia; Maria Immacolata La Rotonda; Martine Appel; Huguette Alphandary; Elias Fattal

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 327 KB
• Volume: 91
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.10063

✦ Synopsis

In this article, microspheres able to induce the controlled release of oligonucleotide/polyethylenimine complexes are proposed. A model oligonucleotide (the oligothymidilate pdT16) was encapsulated within poly(lactide-co-glycolide) microspheres alone or associated with polyethylenimine (PEI) at different nitrogen/phospate (N/P) ratios. Microspheres were prepared by the multiple emulsion±solvent evaporation technique and characterized for morphology, diameter, encapsulation ef®ciency, and release kinetics. The introduction of PEI in the internal aqueous phase resulted in the formation of a soluble complex with pdT16 and in a strong increase of the oligonucleotide encapsulation ef®ciency. PEI affected microsphere morphology inducing the formation of very porous particles yielding to an accelerated release of pdT16. When incubated with HeLa cells, microspheres encapsulating pdT16/PEI complexes allowed both a reduction of the complex toxicity and an improvement of the intracellular penetration of the released oligonucleotide. We conclude that biodegradable microspheres encapsulating oligonucleotides/PEI complexes have a great potential as controlled release system because they allow the sustained release of an oligonucleotide carrier that crosses biological membranes and locates in nucleus.