ATOMIC-FORCE MICROSCOPIC ANALYSIS OF THE INFLUENCE OF THE MOLECULAR-WEIGHT OF POLY(L)LYSINE ON THE SIZE OF POLYELECTROLYTE COMPLEXES FORMEDWITH DNA

We are developing self-assembling micellar vehicles based on multifunc tional block copolymers as well-defined synthetic vehicles suitable fo r safe in vivo delivery of DNA. As a first stage, DNA expression vecto rs (6 kb) were condensed with poly(L)lysine of different molecular wri ghts (3970-224 500) to form polyelectrolyte complexes and analysed by atomic force microscopy (AFM). Discrete complexes were formed in every case, although the highest molecular weight poly(L)lysine preparation (224 500) produced large complexes with significant polydispersity (d iameters ranging from 120-300 nm), while the smallest poly(L)lysine (3 970) produced more homogeneous complexes with diameters ranging from 2 0-30 nm. Poly(L)lysine preparations of molecular weight 59 700 and 23 800 produced complexes of intermediate size and polydispersity. The me an volumes of the complexes formed using poly(L)lysine 224 500 and 397 0 were 606 000 nm(3) and 3700 nm(3), respectively. Polyelectrolyte com plexes formed using low molecular weight poly(L)lysine also showed sig nificantly decreased cytotoxicity. Given restrictions of access to man y cellular targets and the need for good biocompatibility, synthetic v ectors based on DNA condensed with low molecular weight polycations ma y be more appropriately developed for general use.