Structural Modifications of DMPC Vesicles upon Interaction with Poly(amidoamine) Dendrimers Studied by CW-Electron Paramagnetic Resonance and Electron Spin−Echo Techniques

Abstract

This report describes a computer-aided CW- and pulsed-electron paramagnetic resonance (EPR) investigation on the structural modification of dimyristoylphosphatidylcoline (DMPC) vesicles, which occur upon interaction with starburst dendrimers (SBDs). Probes used for this study included doxyl-functionalized stearic acids, with the doxyl group attached at different positions of the stearic chain (5DXSA, 12DXSA, and 16DXSA). Mainly mobility and polarity parameters were evaluated from the analysis of the CW-EPR spectra, whereas the analysis of the decay and modulation of the electron spin−echo (ESE) signal provided information on the structural environment of the paramagnetic center. Due to the interaction with the SBD surface, the vesicle structure became more rigid and ordered. The enhanced rigidity of the structure also caused the tilting of the chains of about 50° with respect to the surface line. The permeability of water at the chain beginning level increased, thus increasing the rotational mobility of the probe. The perturbing effects lessened toward the end of the chains. A fraction of 16DXSA (15%) was in the bent conformation, with the chain inserted into the lipid layer and the two polar heads at the external surface. The interaction with protonated dendrimers caused the swelling of the vesicle structure. This study indicated that the bilayer structure is modified but only partially perturbed by the addition of the dendrimers, and the integrity of the vesicle, as a model cell membrane, is preserved after the interaction with the dendrimers. This is encouraging for the use of the SBDs as drug and gene carriers.

Interaction study between maltose-modified PPI dendrimers and lipidic model membranes

“…Thus, anionic liposomes in the absence of NaCl are approximately 5 nm larger than those prepared in a salty environment ( Table 2). Similar to other interaction studies of dendrimer against liposomes [28,45,46], we observed that the presence of various PPIs in solution influences the hydrodynamic diameter of liposomes. Hydrodynamic diameter of neutral DMPC liposomes increases after the addition of pure PPI to the liposome solution (Table 2), while no (pure Hepes buffer) or nominal (Hepes buffer with NaCl) increase of neutral liposomes' diameter in the presence of OS PPI and DS PPI is recognizable.…”

“…The number of surface groups, their charge and the shapes of molecules affect the strength of interaction. Higher generations of dendrimers affect the structure of the lipid bilayer triggered by number of cationic surface groups [27,45,46]. In the present work, we used cationic unmodified PPI dendrimer and cationic open shell PPI glycodendrimer, but also a neutral dense shell glycodendrimer to investigate their interaction with model lipid membranes.…”

Influence of PAMAM dendrimers on human red blood cells

“…The dendrimer -vesicle interactions are dependent on the membrane composition (e.g., are weak for vesicles that contain a high fraction of PC and are strong for PE-containing vesicles). There are also studies postulating that the integrity of DMPC vesicles upon contact with PAMAM G7 dendrimers is maintained, although there are changes in ordering of the bilayer and rotational mobility of fatty acid chains [9]. The bilayer couple hypothesis explains echinocytic transformation as an effect of an asymmetric expansion of one monolayer [10].…”

Influence of dendrimers on red blood cells

“…3). Interactions between dendrimers and the lipid bilayer have been studied using many methods such as EPR techniques [26][27][28], leakage, lipid mixing and content mixing assays [29][30][31], differential scanning calorimetry [32,33], and atomic force microscopy [34]. Loss of integrity of the RBC membrane which may occur under the influence of dendrimers is accompanied by haemoglobin leakage, which can be measured.…”