Why deliver a statin in form of inclusion complex with hydrophilic cyclodextrin?

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In this work, the effects of simvastatin (SIM), 2-hydroxypropyl)-β-cyclodextrin (HPβCD) and their complex (SIM: HPβCD) on the structure and properties of lipid membranes were investigated for the first time by Langmuir technique combined with polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) spectroscopy. The key findings of this work can be summarized as follows:

  • Simvastatin incorporation in the dimirstoyl phosphatidyl choline (DMPC), cholesterol and mixed Langmuir monolayers led to monolayer fluidization increasing with the increase of the drug concentration, and the extent of unwanted fluidization was much smaller when the drug was delivered in the form of an inclusion complex with HPβCD.
  • The surface pressure studies showed for the first time that the drug delivered to the membrane in the form of the SIM:HPβCD complex dissociates from the complex when it comes into contact with the lipid layer.
  • The cyclodextrin ligand released from the complex remained close to the membrane surface due to weak interactions between the exterior polar part of HPβCD and the polar headgroups of the lipid layer. This interaction facilitates the smooth incorporation of the released lipophilic drug into the membrane.
  • At a longer time-scale or under repeated monolayer compression-decompression on the subphase containing the SIM:HPβCD complex, the penetration of the lipid membrane by SIM was accompanied by some cholesterol (but not DMPC) extraction from the monolayer by the cyclodextrin. The Chol-CD complex formation was evidenced by the thermodynamic data calculated from the hysteresis curves. The removal of cholesterol from the membrane supports the function of statin as the inhibitor of cholesterol biosynthesis in cholesterol-lowering therapies.

Aleksandra Bartkowiak, Dorota Matyszewska, Agata Krzak, Michalina Zaborowska, Marcin Broniatowski, Renata Bilewicz, Incorporation of simvastatin into lipid membranes: why deliver a statin in form of inclusion complex with hydrophilic cyclodextrin, Colloids and Surfaces B: Biointerfaces, 2021, 111784,

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