TY - JOUR
T1 - Structure/function relationships of polyamidoamine/DNA dendrimers as gene delivery vehicles
AU - Braun, Chad S.
AU - Vetro, Joseph A.
AU - Tomalia, Donald A.
AU - Koe, Gary S.
AU - Koe, Janet G.
AU - Middaugh, C. Russell
N1 - Funding Information:
The authors wish to thank both Valentis, Inc. and Dendritic Nanotechnologies for their support of this work. C.S.B. acknowledges financial support from The United States Pharmacopeia Fellowship, and JAV financial support from an American Heart Association Postdoctoral Fellowship (0225425Z).
PY - 2005/2
Y1 - 2005/2
N2 - PAMAM dendrimers are members of a class of polyamine polymers that demonstrate significant gene delivery ability. In this study, a selection of PAMAM dendrimers, spanning a range of sizes (generations 2, 4, 7, and 9) and transfection efficiencies, are characterized by various biophysical methods to search for structural properties that correlate with transfection. Measurements of colloidal properties (size and zeta potential) as a function of charge ratio reveal that highly transfecting dendrimer/DNA complexes have size/zeta potential values between 4 and 8. Circular dichroism (CD) and FTIR spectroscopy of complexes confirm the DNA component remains in B form when associated with all dendrimer generations up to a 5:1 charge ratio (±). Isothermal titration calorimetry and differential scanning calorimetry detect changes that are related to polymer structure and charge ratio but do not directly correlate with transfection efficiency. Despite DNA structural and stability changes detected by CD, FTIR, DSC, and ITC that are similar to those seen with other cationic delivery vehicles [e.g., cationic lipids, peptoids/lipitoids, peptides, polyethyleneimines (PEIs), etc.], clear correlations with transfection activity are not readily apparent. This may be due, at least in part, to the heterogeneity of the complexes.
AB - PAMAM dendrimers are members of a class of polyamine polymers that demonstrate significant gene delivery ability. In this study, a selection of PAMAM dendrimers, spanning a range of sizes (generations 2, 4, 7, and 9) and transfection efficiencies, are characterized by various biophysical methods to search for structural properties that correlate with transfection. Measurements of colloidal properties (size and zeta potential) as a function of charge ratio reveal that highly transfecting dendrimer/DNA complexes have size/zeta potential values between 4 and 8. Circular dichroism (CD) and FTIR spectroscopy of complexes confirm the DNA component remains in B form when associated with all dendrimer generations up to a 5:1 charge ratio (±). Isothermal titration calorimetry and differential scanning calorimetry detect changes that are related to polymer structure and charge ratio but do not directly correlate with transfection efficiency. Despite DNA structural and stability changes detected by CD, FTIR, DSC, and ITC that are similar to those seen with other cationic delivery vehicles [e.g., cationic lipids, peptoids/lipitoids, peptides, polyethyleneimines (PEIs), etc.], clear correlations with transfection activity are not readily apparent. This may be due, at least in part, to the heterogeneity of the complexes.
KW - DNA
KW - Dendrimers
KW - Gene delivery
KW - Structure/function analysis
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U2 - 10.1002/jps.20251
DO - 10.1002/jps.20251
M3 - Article
C2 - 15614818
AN - SCOPUS:14344262752
VL - 94
SP - 423
EP - 436
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
SN - 0022-3549
IS - 2
ER -