Structural investigation into the physical interaction of itraconazole with DPPC

S Radivojev


DPPC (dipalmitoylphosphatidylcholine) is the abundant pulmonary surfactant, providing a stable lung system. Studies of DPPC membrane behaviour with drug molecules has shown the molecular interactions and the drug incorporation within the lipid layers. A potential interaction between DPPC and the inhaled drug could lead to changes in their expected action in the lung. Thus, this study aimed to investigate the interaction of the lipophilic drug itraconazole (ITR) with DPPC. The thermo-physical and structural properties of the DPPC vesicles and the effect of ITR were studied using modulated differential scanning calorimetry (MDSC), small and wide angle X-ray scattering (SWAXS) and optical microscopy. The MDSC results revealed a slight change in the main phase transition of DPPC and in the melting temperature of ITR crystals. The SWAXS profiles demonstrated the increase in nano-heterogeneity of the DPPC vesicles in presence of ITR. This evidenced the partial disruption of the nano-sized multilamellar vesicles of DPPC by the presence of ITR. Additionally, structures in the micrometre range were detected via microscopy and differences in size could be detected in presence of ITR. The observed interaction could (i) impact the drug solubilization, release and absorption and/or (ii) lead to adverse effects associated with the structural changes in the DPPC membrane in the lung.

Key Message

The thermo-physical and structural investigation of the DPPC vesicles revealed an interaction with ITR crystals, suggesting the transformation of the multilamellar vesicles to the smaller size. This might impact the in-vivo behaviour of the drug, namely its potency or adverse effect profile.

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