R. Delong et al., CHARACTERIZATION OF COMPLEXES OF OLIGONUCLEOTIDES WITH POLYAMIDOAMINESTARBURST DENDRIMERS AND EFFECTS ON INTRACELLULAR DELIVERY, Journal of pharmaceutical sciences, 86(6), 1997, pp. 762-764
This study evaluates polyamidoamine PAMAM ''starburst'' dendrimers (ge
neration 3, M-r 6909) as a potential delivery vehicle for oligonucleot
ides. Complexes between dendrimer and phosphorothioate oligonucleotide
s were observed by agarose gel electrophoresis and were positive, nega
tive, or neutral in charge depending on stoichiometry. Complexes were
stable in 50% serum to variations in pH (3, 5, and 10) and ionic stren
gth (0-500 mM). Ultrafiltration and gel filtration characterization in
dicated that the dendrimer:oligonucleotide complexes were primarily <1
00 kD, although some larger complexes were formed at oligonucleotide e
xcess. Use of dendrimers resulted in a 50-fold enhancement in cell upt
ake of oligonucleotide as determined by flow cytometry, and enhanced c
ytosolic and nuclear availability, as shown by confocal microscopy. Th
ese data support the further evaluation of dendrimers for oligonucleot
ide delivery in cell culture and in vivo.