Interactions between some antiretroviral drugs and dmpc model membrane in the presence of magnesium(2+) ions

The drug-membrane interactions have a prominent role in the studies of drug discovery and drug delivery systems. In the present study, a molecular model membrane composed with dimyristoyl phosphatidylcholine (DMPC) was employed with a 5% composition of antiretroviral drugs (Ritonavir, Saqanavir, Efavirenz and Niverapine) to observe the drug-membrane interactions in the presence of Mg2+ ions. Membrane perturbations were observed by using different spectral methods that are horizontal attenuated total reflectance infrared (HATR-IR), Raman, UV-Visible, scanning electron microscope (SEM) and transmission electron microscope (TEM) techniques. The results were shown that there is a clear interaction between the membrane and the drugs. The infrared and Raman techniques showed that ritonavir and saquinavir modify the orientation of the acyl chain in the lipid present in the membrane and this effect become reversible in the presence of Mg2+ ion. When these drugs are added to the model membrane, the C=O stretching and the PO2- antisymmetric double bond stretching bands in lipid are slightly changed. In the case of efavirenz, it shows strong binding with the head group and no interaction on backbone region of the lipid, and these effects are reduced in presence of Mg2+ ions. In the case of Nevirapine, it shows strong binding with head group, acyl chain and backbone region of lipid only in the presence of Mg2+ ions. TEM results show that there is interaction between the DMPC and ritonavir. SEM observations of human erythrocytes incubated with saquinavir revealed that the drug induced changes in the cells' normal shape. In the absence of Mg2+ ions, the order of interaction of drugs on lipid is Ritoanvir > Saquinavir> Efavirenz> Nevirapine. In the presence of Mg 2+ ions, the order is Nevirapine> Efavirenz> Saquinavir> Ritonavir. These interaction studies may be useful in designing and developing efficient drug delivery systems.