INTERACTION OF MACROMOLECULAR PRO-DRUGS WITH LIPID MODEL MEMBRANE - CALORIMETRIC STUDY OF 4-BIPHENYLACETIC ACID LINKED TO ALPHA,BETA-POLY(N-HYDROXYETHYL)-DL-ASPARTAMIDE INTERACTING WITH PHOSPHATIDYLCHOLINE VESICLES

The effect of 4-biphenylacetic acid (BPAA) covalently linked to α,β-poly(N-hydroxyethyl)-dl-aspartamide (PHEA) on the thermotropic properties of dipalmitoylphosphatidylcholine (DPPC) liposomes was investigated by differential scanning calorimetry (DSC). Addition of increasing amounts of PHEA-BPAA adduct to a suspension of phospholipid vesicles modified the thermotropic gel-to-liquid crystalline phase transition by decreasing the enthalpy changes ΔH with concomitant broadening of the peak without variations in the transition temperature (Tm). These effects are interpreted in terms of a deep interaction of BPAA bound to the polymer with the apolar moiety of the lipid bilayer. The amount of drug able to suppress the phase transition was estimated by plotting the enthalpy changes of the transition vs mole ratio of added drug, and extrapolating to ΔH = 0. The trend in the ΔH values yields a possible 1 : 1 stoichiometry for the interaction between drug and phospholipid. Experiments carried out at different pH values provided information about the species involved in the interaction with DPPC liposomes. Similar results can be expected in the case of the cell membrane. © 1990.