Effect of grafted polyethylene glycol (PEG) on the size, encapsulation efficiency and permeability of vesicles

Abstract

Liposomes have been prepared by the vesicle extrusion method (VETs) from mixtures of dipalmitoylphosphatidylcholine (DPPC), phosphatidylinositol (PI) and dipalmitoylphosphatidylethanolamine with covalently linked poly(ethylene glycol) molecular mass 5000 and 2000 (DPPE-PEG 5000 and DPPE-PEG 2000) covering a range of 0-7.5 mole%. The encapsulation of D-glucose has been studied and found to be markedly dependent on the mole% DPPE-PEG. The permeability of the liposomes to D-glucose has been measured both as a function of temperature and liposome composition. The permeability coefficients for D-glucose increase with mole% DPPE-PEG 5000 and with temperature over the range 25-50 degrees C. The activation energies for glucose permeability range from 90 to 23 kJ mol(-1). The decrease in activation energy with increasing temperature is attributed to an increasing number of bilayer defects as the liposome content of PEG-grafted lipid is increased. The dependence of D-glucose encapsulation as a function of PEG-grafted lipid content is discussed in terms of the conformation of the PEG molecules on the inner surface of the bilayer. For liposomes containing DPPE-PEG 5000 the relative percentage encapsulation of glucose, assuming that the PEG surface layer excludes glucose, is comparable to that predicted from the mushroom and brush conformational models.

Hybrid, Nanoscale Phospholipid/Block Copolymer Vesicles

“…In summary, these results imply that film-rehydration of POPC and PB-PEO block copolymers blends yields nanometer-sized hybrid vesicles over the entire range of compositions studied. The results are significantly different from those obtained in a previous study of micrometer-sized hybrid GUVs formed from POPC and PB-PEO, even though this comprised a higher molecular weight polymer, i.e., PB 46 -PEO 30 (M W for PB and PEO blocks: 2500 and 1300, respectively), and a different preparation method [15]. In the respective study, hybrid GUVs formation was inefficient at high lipid composition (>65 mol %), while at intermediate lipid compositions (35-65 mol %) GUVs were not formed at all.…”

“…Simulation and experimental studies have suggested block copolymers with molecular weights below 3 kDa or membrane thicknesses below 7 nm adopt more stretched and ordered membrane configuration (compared to more flexible entangled configuration of long block copolymers), which is consistent with the strongly segregated state of lipids [26,27], making mixing energetically more favorable. To re-confirm this effect, we also performed flow cytometry on nanoscale vesicles prepared from mixtures of POPC and the longer polymer, PB 46 -PEO 30 (M W = 3800). The dot plots results shows the fraction of hybrids to measure 17%-36%, suggesting that the mixing of this copolymer with lipids is indeed less efficient ( Figure S1 and Table S1).…”

“…PB-PEO (PB 22 -PEO 14 , average molecular weight for the PB and PEO block: 1200 and 600, respectively; PB 46 -PEO 30 , average molecular weight for the PB and PEO block: 2500 and 1300, respectively ) was purchased from Polymer Source (Dorval, Quebec, Canada). 1-Palmitoyl-2-oleoylsn-glycero-3-phosphatidylcholine (POPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(lissamine rhodamine B sulfonyl) (Rho-PE), and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(1-pyrenesulfonyl)(pyrene-PE) were purchased from Avanti Polar Lipids (Alabaster, AL, USA).…”

“…We hypothesize that this observation is related to the surface area-to-volume ratio, which follows a similar trend if the radii obtained for the (hybrid) vesicles by DLS are used as the input for the calculation of the volumes ( Figure S2). A second contribution to the observed phenomenon may come from the excluded-volume effect of the polyethylene glycol (PEG)-block of the polymers, as observed for PEG-ylated liposomes [30]. Figure 5.…”

“…Parameters controlling the self-assembly of lipids with block copolymers (forming hybrids GUVs), and the resulting phase behavior, are the mole fraction of the constituting amphiphiles, as well as the nature of the amphiphiles themselves [14][15][16][17]. Nam et al [15] observed efficient mixing of PB 46 -PEO 30 [polybutadiene-b-poly(ethylene oxide)] and POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine) to occur only at polymer concentrations above 65%, while Schulz et al [17] found hybrid GUVs to form at all investigated molar ratios of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and polyisobutylene-b-PEO. The membrane thickness of the polymers and the melting transition temperature of the lipids have been demonstrated to significantly affect the formation, morphology and/or stability of hybrid GUVs, as well [14].…”