Pr. Dash et al., Factors affecting blood clearance and in vivo distribution of polyelectrolyte complexes for gene delivery, GENE THER, 6(4), 1999, pp. 643-650
Self-assembling polycation/DNA complexes represent a promising synthetic ve
ctor for gene delivery. However, despite considerable versatility and trans
fectional activity in vitro, such materials are quickly eliminated from the
bloodstream following intravenous injection (plasma alpha half-life typica
lly less than 5 min). For targeted systemic delivery a more prolonged plasm
a circulation of the vector is essential. Here we have examined factors con
tributing to rapid elimination of poly(L-lysine) (pLL)/DNA complexes from t
he bloodstream, and implicate the binding of proteins to the polyelectrolyt
e complexes as a likely cause for their blood clearance. pLL/DNA complexes
reisolated from serum associate with several proteins depending on their ne
t charge, although the major band on SDS-PAGE comigrates with albumin. Seru
m albumin binds to pLL/DNA complexes in vitro, forming a ternary pLL/DNA/al
bumin complex which regains some ethidium bromide fluorescence and fails to
move during agarose electrophoresis. Albumin also causes increased turbidi
ty of complexes, and reduces their zeta potential to the same level (-16 mV
) as is measured in serum. We propose that rapid plasma elimination of poly
cation/DNA complexes results from their binding serum albumin and other pro
teins, perhaps due to aggregation and phagocytic capture or accumulation of
the ternary complexes in fine capillary beds.