Spin-label electron spin resonance studies of micellar dispersions of PEGs-PEs polymer-lipids

Conventional electron spin resonance (ESR) spectroscopy of different positional isomers of phosphatidylcholine spin labels (n-PCSL; n=5, 7, 10, 12, 14, and 16) has been used to study micellar dispersions made of poly(ethylene glycol)s-phosphatidylethanolamines (PEGs-PEs) polymer-lipids. Such aggregates are currently used as long circulating drug delivery systems "in vivo." We varied both the hydrocarbon chain length and the polymer size of the polymer-lipids. The dependence of the lipid-chain packing density on temperature and on label position as well as the flexibility and polarity profiles with position of chain labeling have been established for the PEGs-PEs micellar dispersions. The results show both similarity and differences either with common micellar dispersions of single chained lyso-palmitoylphosphatidylcholine (C(16)Lyso-PC) or with lamellar dispersions of double chained dipalmitoylphosphatidylcholine (DPPC). Well defined chain flexibility gradients of the same overall shape are obtained in the considered dispersions. However, the mobility of the first acyl chain segments is appreciable higher in micelles of polymer-lipids than in bilayers of DPPC and it becomes indistinguishable at the chain termini. A trend of decreasing polarity on moving toward the bilayer interior is seen in DPPC bilayers, whereas biphasic polarity profiles are obtained in micelles of polymer-lipids and C(16)Lyso-PC. Moreover, the properties of the PEGs-PEs micelles do not depend on the length of the hydrocarbon chain of the polymer-lipids but are slightly influenced by the size of the polymer.