Temozolomide (TMZ) is the first-line treatment for
Glioblastoma Multiforme (GBM). After administration, TMZ is rapidly converted into its active metabolite (
MTIC). However, its pharmacological activity is reduced due
MTIC low bioavailability in the brain. Since drugs' permeability through
biological barriers and
tumor cell membranes affects its bioavailability, the ability of
MTIC to interact with the
biological membranes presents a major contribution on its pharmacological properties and activity. Biomembrane models mimic the physiological conditions, allowing to predict the
drug's behavior at
biological membranes and its effects on
drug biodistribution profiles. In this work,
lipid bilayer models using
liposomes were applied for the
drug-membrane interaction studies. The zwitterionic
phospholipid, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (
DMPC), and
cholesterol were chosen for the composition of the model, since they represent the major components of the membranes of GBM cells and brain capillary endothelial cell. Thus, the molecular interactions between
MTIC and these models were studied by the evaluation of the partition of the
drug into the
phospholipid's membrane, its location within the bilayer and its effect on the fluidity of the membrane. The attained results suggest that the composition of membranes affects drugs partition, showing that
drug biodistribution depends not only on its physicochemical features, but also depends on the characteristics of the membrane such as the packing of the
lipid molecules. Also,
MTIC exhibited low affinity to
biological membranes, explaining its low bioavailability on the target cells.