The objectives of this work were to study the interaction of an antisense oligonucleotide (ISIS 2302) with poly-L-lysine (PLL) and protamine salts, to determine the physico-chemical characteristics of the resulting complex systems and to analyze the influence of permeation enhancers (Na-chenodeoxycholate and Na-caprate) on the dissociation of the complexes. Specific conductivity, zeta potential, particle size distribution and dialysis studies of the resulting complex systems were performed. Conductometric titration defined the molar ratios between the ionic species in the complex. Zeta potential data confirmed the conductometric equivalence points and explained the good physical stability of charged complexes when compared to neutral complexes (+/-40 mV for PLL-based complexes and +/-25 mV for protamine sulfate complexes). The particle size was less than 175 nm for most systems. The incorporation of Na-chenodeoxycholate promoted complex dissociation, while Na-caprate gave opposite results. An increase in the ionic strength of the environment had a destabilizing effect and promoted dissociation of the complexes.