CATIONIC DENDRIPLEXES FOR GENE THERAPY REQUIRES AT LEAST 5h TO EQUILIBRATE

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Date
2012-03-23
Authors
Akinleye, M.O.
Uchegbu, I.F.
Coker, H.A.B.
Schatzlein, A.G.
Journal Title
Journal ISSN
Volume Title
Publisher
Academic Sciences
Abstract
The task of developing a non-viral vector system for efficient delivery of drugs and genes has been a major concern to molecular scientists. Several efforts at formulating DNA-polycation complexes that show relatively consistent particle size and shape has not yielded perfect outcome. Some of these formulation variables can be exploited for optimum achievement towards development of DNA-polmer complexes of required nanosize. The objective of the study was to investigate the hydrodynamic size and zeta potential of complexes by dynamic light and electrophoretic light scattering with a view to formulating DNA/DAB complexes of consistent particle size and shape. Stock solutions of DAB16 (1 & 10 mgmL-1) and DNA (Calf thymus) [1 & 10 mgmL-1] concentrations were prepared in 5% dextrose solution and deionised water respectively. DNA-Dendrimer Complexes (DNA/DAB16) were formulated based on a nitrogen to phosphate (N:P) ratio. Samples were characterized using a Zeta sizer 3000 HAS for hydrodynamic size; surface zeta potentials and Transmission electron microscope (TEM) for imaging. Evidence showed that a N:P ratio in excess of 8 and/ or a DNA concentration in excess of 250µg/ml lead to non-colloidal complexes. It was also demonstrated that higher levels of dendrimer to dendriplex lead to a diminished dendriplex surface charge. The results also confirmed that as the binding time of Dendriplexes increases, the particle size of the complexes decreases while the zeta potential increases. It can be concluded based on our results that a period of between 5 and 8 hour could be appropriate for dendriplex binding that will give a relatively consistent particle size and shape for efficient DNA delivery
Description
Keywords
DNA-DAB Complex , Polypropylenimine dendrimers , Gene delivery , Equilibration time
Citation
CATIONIC DENDRIPLEXES FOR GENE THERAPY REQUIRES AT LEAST 5h TO EQUILIBRATE,AKINLEYE MO1,UCHEGBU IF, COKER HAB,SCHATZLEIN AG. International Journal of Pharmacy and Pharmaceutical Sciences,Vol 4, Suppl 3, 2012