Exploring the interactions of irbesartan and irbesartan–2-hydroxypropyl-β-cyclodextrin complex with model membranes

Abstract

The interactions of irbesartan (IRB) and irbesartan-2-hydroxypropyl-β-cyclodextrin (HP-β-CD) complex with dipalmitoyl phosphatidylcholine (DPPC) bilayers have been explored utilizing an array of biophysical techniques ranging from differential scanning calorimetry (DSC), small angle X-ray scattering (SAXS), ESI mass spectrometry (ESI-MS) and solid state nuclear magnetic resonance (ssNMR). Molecular dynamics (MD) calculations have been also conducted to complement the experimental results. Irbesartan was found to be embedded in the lipid membrane core and to affect the phase transition properties of the DPPC bilayers. SAXS studies revealed that irbesartan alone does not display perfect solvation since some coexisting irbesartan crystallites are present. In its complexed form IRB gets fully solvated in the membranes showing that encapsulation of IRB in HP-β-CD may have beneficial effects in the ADME properties of this drug. MD experiments revealed the topological and orientational integration of irbesartan into the phospholipid bilayer being placed at about 1nm from the membrane centre.

The investigation of the interaction of Armodafinil with membrane lipids by using DPPC model membrane system

“…Such observed changes in hydrophilic parts of the lipids induced by ARM may further cause some alterations in main transition parameters such as broadening of the transition curve, a decrement in Tm, CU and ΔH as also found in DSC data (FigureTable 1) (7-9,[15][16][17]. These observations can be referred partition of ARM molecule into lipids (7-9,15- 17,36-37).…”

Binding Ability of Lacosamide to Phosphatidylcholine Lipids and Cholesterol Effects

“…ΔH and Tm); FT-IR spectroscopy offers data about lipid dynamics (fluidity), lipid acyl chain flexibility (ordering), hydration state. Thus, these techniques have been extensively utilized in these kinds of works 13,[17][18][19]22,[24][25][26][27][28] .…”

“…Displaying a very high complexity with varied lipid, proteins and carbohydrates, biological membranes are accompanied by some disadvantages to examine drug-lipid interactions because of difficulties in the interpretation of the results. Thus, usage of model membrane systems which offer specific information is a general approach for such studies 18,[22][23][24] . Specifically, the composition of outer leaflet of plasma membranes of mammalian cells consists of phosphatidylcholines (PC) and sphingomyelin, which together reach to abundant amounts in most membranes, and the other main components such as cholesterol (CHO) found up to 50 mol %23,25.…”

“…By monitoring such changes in model membrane systems the information about the degree of interaction and behaviour of the drug in real membrane systems can be obtained 14,17,[26][27] . Similarly, in the present study we aimed to provide information for binding ability of LCM with PC membrane lipids, and designed our experiments on a well-established molecular models of biomembranes 13,18,22,24,26 , multilamellar vesicles (MLVs) formed by DPPC and CHO lipids, as similarly performed for phenytoin, 12 and gabapentin and levetricetam 13 . Indeed, in the absence and the presence of CHO (10 mol%), the effects of LCM at different concentrations (1-10-20 mol%) on biophysical parameters of DPPC MLVs were investigated.…”

“…Indeed, in the absence and the presence of CHO (10 mol%), the effects of LCM at different concentrations (1-10-20 mol%) on biophysical parameters of DPPC MLVs were investigated. To achieve this, Fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) were utilized as in earlier studies 12,13,[17][18][19]22,[24][25][26][27] .…”