It sounds like a pretty nasty thing to do to an expensive gel filtration column. If I had to do it, I would make up a big batch of liposomes of the proper type and put that in the elution buffer at as high a concentration as seems reasonable. Then I would run it through the column until the concentration of liposomes coming out of the column is equal to the concentration going in. You might be able monitor that by UV absorbance (really light scattering) because the liposome size is so large that they will scatter a lot of light. However, the light scattering might be so large that the detector saturates, in which case you could take fractions, dilute them, and measure the light scattering off-line.

It seems like something that would take some trial and error as well. Have you or anyone ever purified liposomes using GPC, without any additional pre-saturation steps? I wish it didn't require that extra step.

If your drug is water-soluble, you can use dialysis to remove the free drug from the liposomes instead of gel filtration. Alternatively, you can use a so-called desalting spin column, which is gel filtration combined with centrifugation. The advantage of the spin column technique is that the applied sample does not increase in volume the way it does in normal gel filtration chromatography. It is also faster.

If your liposomes are reasonably concentrated, I don't think you need to pre-saturate the gel filtration medium. You may suffer some loss of liposomes, but this loss may be acceptable, and you won't dilute your drug-filled liposomes with drug-free liposomes from the column.