Poster Presentation 2014 International Biophysics Congress

QCM-D study of the interaction of siRNA with lipidic cubic phase delivery vehicles (#559)

Behnoosh Tajik-Ahmadabad 1 2 , Frances Separovic 1 , Tash Polyzos 2
  1. University of Melbourne, Melbourne, VIC, Australia
  2. CSIRO Material Science and Engineering, Melbourne, VIC, Australia

The unique architecture of bicontinuous cubic lipidic phases renders these materials as an ideal medium for the encapsulation of small interfering RNA (siRNA)1-2. However, the ability to exert control over siRNA uptake and release from these systems, crucial to current and prospective applications for cubic phases in gene silencing, remains elusive. Herein biophysical studies were undertaken to study the binding and release of siRNA from cationic non-lamellar lipidic nanoparticles (LNP) using time-resolved quartz crystal microbalance (QCM-D) and small angle X-ray scattering (SAXS). 

We have developed a multilayer strategy3 to tether LNPs to the QCM crystal surface to permit the study of the binding and release of siRNA from various LNP formulations. QCM results show the establishment of rapid binding kinetics of the siRNA to the tethered LNPs, which is independent of the cationic lipid to siRNA charge ratio (1:1 and 1:4). Furthermore, the release of siRNA from LNP was studied under acidic conditions, similar to endosomal pH, using QCM-D and SAXS measurements. Direct siRNA release from LNP-siRNA complexes was not observed with the acid titrations and other factors, including aggregate disruption, are required to trigger the release of siRNA from cationic non-lamellar LNPs.       


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2.      Leal C, Bouxsein NF, Ewert KK, Safinya CR. (2010) J. Am. Chem. Soc. 132: 16841-7.

3.     Fraser SJ, Mulet X, Martin L, Praporski S, Mechler A, Hartley PG, Polyzos A, Separovic F. (2012) Langmuir. 28:620-7.