Arch Biochem Biophys 2025 Jul 03;769:110408. doi: 10.1016/j.abb.2025.110408.

Lipid saturation modulates the interaction of anastrozole with biointerfaces.

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The interaction of anastrozole, an anticancer drug, with lipid biointerfaces was investigated using Langmuir monolayers of DPPS (saturated lipid) and POPS (unsaturated lipid) to model different membrane environments. Surface pressure-area isotherms revealed that anastrozole induced a slight condensation in DPPS monolayers, while significantly condensing POPS at higher surface pressures, indicating attractive interactions with the unsaturated lipid. The surface dilatational modulus remained largely unaffected for DPPS but decreased for POPS, highlighting a reduction in the surface elasticity. Brewster Angle Microscopy (BAM) images showed the formation of domains in anastrozole-POPS monolayers, whereas DPPS monolayers retained a homogeneous morphology. Infrared spectroscopy indicated that anastrozole increased the conformational order of DPPS alkyl chains while decreasing order in POPS, further supporting the lipid-specific effects of the drug. These findings suggest that lipid saturation plays a critical role in modulating drug-lipid interactions, with anastrozole exhibiting a higher affinity for unsaturated lipids, potentially influencing its bioavailability and mechanism of action at biomembrane interfaces. The results provide insights into the physicochemical behavior of anastrozole in lipid-rich environments, which may be relevant for drug delivery and therapeutic applications.

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