A comparative study on the ability of various polymers to interact with a biomembrane model was carried out by differential scanning calorimetry (DSC). The investigated samples were a water soluble polymer, the alpha,beta-polyaspartylhydrazide (PAHy) and its derivatives containing polyethylene glycol (PEG(2000)) (Sample PAHy-PEG(2000)), or hexadecylamine (C-16) (sample PAHy-C-16) or both compounds (sample PAHy-PEG(2000)-C-16). Some samples are able to arrange themselves as micellar structures and to interact potentially with the membrane surface so as to favor the release of the drug near the target membrane and consequently to improve drug adsorption processes. First, the interaction of all polymers with a biomembrane model made of multilamellar vesicles of mixed (80:20, mol:mol) dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidic acid (DMPA), has been studied (pH 7.4), then the interaction of Ketoprofen (KPF) as free drug or released from PAHy-C-16 micelles with the same biomembrane model has been investigated. Differential scanning calorimetry appears to be a suitable technique to follow the interaction of all prepared samples as well as the transfer kinetics of a drug from PAHy-C-16 micelles to a biomembrane model. The drug release kinetics, from PAHy-C-16 micelles, was compared with the transfer of free drug (after dissolution from a solid form) by evaluating their effects on the thermotropic behavior of DMPC/DMPA multilamellar vesicles. (C) 2004 Elsevier B.V. All rights reserved.