Synthesis and assembly of poly(ethylene glycol)-lipids with mono-, di-, and tetraacyl chains and a poly(ethylene glycol) chain of various molecular weights

We synthesized a series of amphiphiles with poly(ethylene glycol) [MW 2000 (PEG20), 5000 (PEG50), 12 500 (PEG125)] as a headgroup and one, two, or fou r palmitoyl chains (1C16, 2C16, or 4C16), using a lysine monodendron as a c onnector. The relationship between the hydrophilic-hydrophobic balance of t he multiacyl PEG-lipids and the physicochemical characteristics in self- or co-assembly with phospholipids were studied. The PEG-lipids were easily sy nthesized by combination of a general liquid-phase peptide synthesis and th e acylation of an amino acid. The PEG part of the PEG-lipid films was cryst allized to show a typical spherulite pattern. The thermal properties and mi croscopic observation revealed the phase separation of PEG and acyl chain p arts. The critical micelle concentrations (cmcs) mainly depend on the numbe r of acyl chains rather than the molecular weight of the PEG chain, althoug h the area per molecule is dependent on the molecular weight of the PEG cha in rather than the number of the acyl chains. The gel-to-liquid crystalline phase transition temperature was increased with the increasing number of a cyl chains and the decreasing molecular weight of the PEG chain. The PEG-li pids in the aqueous dispersions assemble to take fibrous structures with bi molecular thickness because of the intermolecular hydrogen bonding. The PEG -lipids were immobilized onto the surface of the phospholipid vesicles by s imply adding their aqueous dispersions to the vesicle dispersion; however, they dissociated from the vesicles on dilution of the mixed dispersion beca use they were incorporated into the vesicles in an equilibrium state. To pr event the dissociation of the PEG-lipids, at least two and four acyl chains were required for PEG with M-W 5000 and 12 500, respectively. The aggregat ion of the vesicles by the addition of water-soluble polymers was significa ntly inhibited with the increasing molecular weight of the PEG chain. For t he tight immobilization of the PEG-lipids with the long PEG chain onto the vesicular surface, an increased number of acyl chains is necessary, and the surface modification with the long PEG chains significantly increases the dispersion stability of the vesicles.