Often the polymeric drug carriers in the assembled state are more toxic for cells than when in a dissociated state. The reasons of this significant increase of toxicity for the cell when assembled as well as the ways to reduce it are still unknown. Although the increased toxicity is sometimes attributed to the ability of the drug carriers to dissolve membrane lipids in the carrier cores, this remains as a speculative idea. During the contact with cell membranes the drug carriers may suck phospholipids and other constituents of cells into the cores, thus irreversibly damaging them. We investigate this problem with the Self-Consistent Mean Field Theory. The result of our analysis will elucidate the real effect of the aggregate on the cell membrane and give a comprehensive explanation of the increase of the toxicity, thus opening the door to strategies to reduce such toxicity.

The binding of the drug to the micelles described above is not very strong and the micelles normally dissociate when the bulk polymer concentration is below the CMC. This can be viewed as a disadvantage in some applications. If a stronger binding is required, the hydrophobic drug can be chemically attached to a hydrophilic linear polymer, as a side chain. Such a structure is known as a prodrug or polysoap. In an aqueous solution, the side chains containing drug form the core of the micelle, while the hydrophilic main chain forms the corona, mostly comprising loops. Such an aggregate is more stable than the simple micelle and does not release the drug until a chemical signal is given, for example, enzymatic degradation of the main chain at the target site. Since the only existing models are phenomenological models of polysoaps, the SCMFT method provides an important alternative that promises to give new and detailed information out of the reach for current capabilities.