title: Biophysical and structural characterisation of nucleic acid complexes with modified cyclodextrins using circular dichroism.
abstract: Modified cyclodextrins (CDs) have shown great promise as non-viral gene and siRNA delivery vectors in a range of in vitro and in vivo studies. In the current study, structural and biophysical characterisation of selected CDs was carried out to enhance our understanding of their interaction with nucleic acids. The methods used for such characterisation were dynamic light scattering, zeta potential measurements and circular dichroism. Variations in the chemistries of individual CDs and in the type of formulation were shown to affect key properties of complexes such as size, surface charge and nucleic acid conformation. Furthermore, the effects of temperature and pH on the conformation of nucleic acids were investigated. pH studies were intended to mimic the conditions encountered by cationic complexes during endocytosis. Circular dichroism studies revealed that changes occurred in DNA and siRNA conformation upon complexation with CDs and when exposed to increasing temperature and decreasing pH. Overall, siRNA appeared to be more susceptible to conformational changes although complexation of siRNA with CDs tended to have a stabilising effect.
authors.affiliation: Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland.
authors.forename: Aoife M
authors.initials: AM
authors.lastname: O'Mahony
authors.forename: Michael F
authors.initials: MF
authors.lastname: Cronin
authors.forename: Anthony
authors.initials: A
authors.lastname: McMahon
authors.forename: James C
authors.initials: JC
authors.lastname: Evans
authors.forename: Kathleen
authors.initials: K
authors.lastname: Daly
authors.forename: Raphael
authors.initials: R
authors.lastname: Darcy
authors.forename: Caitriona M
authors.initials: CM
authors.lastname: O'Driscoll
mesh_terms: D001703:Biophysics; D002942:Circular Dichroism / Q000379:methods; D003505:Cyclodextrins / Q000737:chemistry*; D004705:Endocytosis; D006863:Hydrogen-Ion Concentration; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000737:chemistry*; D013057:Spectrum Analysis; D013696:Temperature
chemical_list: D003505:Cyclodextrins; D009696:Nucleic Acids
keywords: biopharmaceuticals; characterization; circular dichroism; non-viral gene delivery; plasmid DNA; siRNA