Biophysical Correlates on the Composition, Functionality, and Structure of Dendrimer–Liposome Aggregates

[Image: see text] Interaction between negatively charged liposomes and cationic polyamidoamine dendrimers of different generations was investigated through size, zeta potential, turbidity, electron microscopy, atomic force microscopy, fluorescence spectroscopy, and calorimetric studies. Liposomes with the binary combination of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) + dihexadecyl phosphate, DPPC + 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol, DPPC + 1,2-dipalmitoyl-sn-glycero-3-phosphate, and DPPC + 1,2-dipalmitoyl-sn-glycero-3-phosphoethanol were stable up to 60 days. The electrostatic nature of dendrimer–lipid bilayer interaction was evidenced through charge neutralization and subsequent reversal upon added dendrimer to liposome. Dendrimer–liposome interaction depended on its generation (5 > 4 > 3) in addition to the charge, head groups, and hydrocarbon chain length of lipids. Fluorescence anisotropy and differential scanning calorimetry studies suggest the fluidization of the bilayer, although the surface rigidity was enhanced by the added dendrimers. Thermodynamic parameters of the interaction processes were evaluated by isothermal titration and differential scanning calorimetric studies. The binding processes were exothermic in nature. The enthalpy of transition of the chain melting of lipids decreased systematically with increasing dendrimer concentration and generation. Dendrimer–liposome aggregates were nontoxic to healthy human blood cell, suggesting the potential of such aggregates as drug delivery systems.