An amino acid-based amphoteric liposomal delivery system for systemic administration of siRNA.

ABSTRACT: We demonstrate a systematic and rational approach to create a library of natural and modified, dialkylated amino acids based upon arginine for development of an efficient small interfering RNA (siRNA) delivery system. These amino acids, designated DiLA₂ compounds, in conjunction with other components, demonstrate unique properties for assembly into monodisperse, 100-nm small liposomal particles containing siRNA. We show that DiLA₂-based liposomes undergo a pH-dependent phase transition to an inverted hexagonal phase facilitating efficient siRNA release from endosomes to the cytosol. Using an arginine-based DiLA₂, cationic liposomes were prepared that provide high in vivo siRNA delivery efficiency and are well-tolerated in both cell and animal models. DiLA₂-based liposomes demonstrate a lin

SUBMITTER: Adami RC 

PROVIDER: S-EPMC3129796 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature