Amphiphilic polyallylamine based polymeric micelles for siRNA delivery to the gastrointestinal tract: In vitro investigations

Targeting the gastrointestinal (GI) tract represents a promising strategy for local or systemic delivery of nucleic acid-based therapeutics. The development of a nano-carrier for siRNA delivery via the GI tract would enable localised therapy for a range of gastrointestinal diseases. Previously, nano-sized polymeric micelles (PM) formed by a variety of amphiphilic poly(allylamine) (PAA) derivatives have shown potential for oral delivery of hydrophobic drugs and bioactive peptides. The aim of this study was to evaluate the ability of these amphiphilic PAA-based PM for siRNA delivery via the GI tract. The physicochemical characteristics of PAA.siRNA transfection complexes and their biological efficacy in vitro were investigated. Physicochemical profiles demonstrated that PAAs and siRNA self-assembled into complexes with nanosized diameters (150-300 nm) and cationic surface charge (+ 20 to 30 mV). The PAA.siRNA complexes were stable in the presence of salt solutions and simulated gastric/intestinal fluids. In undifferentiated Caco-2 cells, PAA.siRNA complexes achieved up to 35% cellular uptake, with successful siRNA release from endosomes/lysosomes and significant luciferase gene knockdown. These results highlight the potential of these nano-sized PM for siRNA oral delivery via the GI tract for treatment of gastrointestinal diseases. (C) 2013 Elsevier B. V. All rights reserved.