A 2(4) factorial design is used to optimize the adsorption conditions of the hydrophilic anionic polyelectrolytes, Carboxymethylchitin (CMC) and Carboxymethyl/Glycolchitin (CO) onto liposomes at physiological ionic strength (I) and pH using phosphate buffered saline (PBS, I = 154 mM, pH = 7.4). Positive ([+]) or high surface affinity liposomes (DSPC:CHOL:DMTAP, 5:4:1), and Neutral ([N]) or low surface affinity liposomes (DSPC: CHOL, 1:1) were used as adsorption surfaces. Results of the calculations of the main effects indicate that polymer molecular weight (mwt), Surface Affinity (S), Number of Adsorption Shots (Sh), Temperature (T), and the combinations mwt x S, mwt x Sh are the most important process parameters. Results of a study conducted at T = 37 degrees C shaw that no loss occurs from the positive surface at the highest particle concentration, N-p = 4.043 x 10(11). Finally, the extent of polymer-induced particle aggregation is decreased when the diameter of the uncoated liposomes is doubled from 0.22 to 0.45 mu m. These results are as expected, given the stiffness and the dimensions of the macromolecules.