PEG-lipids

The Jing group investigated their poly(L-lysine)-6-poly(L-phenylalanine) vesicles for the development of synthetic blood, since PEG-lipid vesicles were previously used to encapsulate hemoglobin to protect it from oxidation and to increase circulation time. They extended this concept and demonstrated that functional hemoglobin could be encapsulated into their vesicles. The same polypeptide material was also used to complex DNA, which caused the vesicles to lose their... 

Hatakeyama H, Akita H, Kogure K, Oishi M, Nagasaki Y, Kihira Y, Ueno M, Kobayashi H, Kikuchi H, Harashima H (2007) Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid. Gene Ther 14 68-77... 

Proteins can be immobilized on the cell surface with the use of a short, single stranded DNA (ssDNA) attached to the end of a PEG chain (ssDNA-PEG-lipid) [114—116, 119, 125]. First, an ssDNA-PEG-lipid is prepared by conjugating... 

Fig. 8 Immobilization of urokinase on the surfaces of islet cells, (a) Surface modification (/) chemical structure of ssDNA-PEG-lipid, and (2) ssDNA-PEG-lipid anchoring to the cell membrane. (b) Introduction of a complementary ssDNA onto urokinase, which was first modified with a madeimide group by a cross-linker, EMCS. (c) Urokinase-immobilization through DNA...

Fig. 9 Surface modification of cells with ssDNA-PEG-lipid. (a) Real-time monitoring of PEG-lipid incorporation into a supported lipid membrane by SPR. (r) A suspension of small unilamellar vesicles (SUV) of egg yolk lecithin (70 pg/mL) was applied to a CH3-SAM surface. A PEG-lipid solution (100 pg/mL) was then applied, (ii) Three types of PEG-lipids were compared PEG-DMPE (C14), PEG-DPPE (C16), and PEG-DSPE (C18) with acyl chains of 14, 16, and 18 carbons, respectively, (b) Confocal laser scanning microscopic image of an CCRF-CEM cell displays immobilized FITC-oligo(dA)2o hybridized to membrane-incorporated oligo(dT)20-PEG-lipid. (c) SPR sensorigrams of interaction between oligo(dA)2o-urokinase and the oligo (dT)2o-PEG-lipid incorporated into the cell surface, (i) BSA solution was applied to block nonspecific sites on the oligo(dT)20-incorporated substrate, (ii) Oligo(dA)20-urokinase (solid line) or oligo(dT)20-urokinase (dotted line) was applied...

Fig. 10 Confocal laser scanning microscope images of islets with urokinase (UK) immobilized on the membrane. The green fluorescence indicates positive immunostaining for UK. (a) Islets were modified with oligo(dT)2o-PEG-lipid (C16) or (b) oligo(dT)2o-PEG-lipid (C18) then, oligo (dA)2o-UK was added to the media, (c) Unmodified islets with (left) and without (right) oligo (dT)20-PEG-lipids added to the solution. Insets. Bright field images. Scale bars 100 pm...

Fig. 11 Islets with immobilized urokinase (UK-islets) were tested for the ability to dissolve fibrin, (a) Fibrin in the plate gel medium was dissolved by UK-islets (clear areas). Fifty islets were applied to each spot, and the plate was observed after incubation at 37 °C for 14 h. (1) untreated islets (2) UK-islets treated with oligo(dT)2o-PEG-lipid (C16), just after preparation (3) UK-islets treated with oligo(dT)2o-PEG-lipid (C16) lost activity after 2 days in culture (4) UK-islets treated with oligo(dT)20-PEG-lipid (C18), just after preparation and (5) UK-islets treated with oligo (dT)20-PEG-lipid (C16) lost activity after 2 days in culture, (b) Morphology of UK-islets after 1 and 7 days of culture...

The ssDNA-PEG-lipid provides versatility in cell surface modifications. It enables the immobilization of a broad spectrum of proteins and low molecular... 

Inui O, Teramura Y, Iwata H (2010) Retention dynamics of amphiphilic polymers PEG-lipids and PVA-Alkyl on the cell surface. ACS Appl Mater Interfaces 2 1514—1520... 

Teramura Y, Iwata H (2009) Surface modification of islets with PEG-lipid for improvement of graft survival in intraportal transplantation. Transplantation 88 624-630... 

Teramura Y, Ln M, Kawamoto T et al (2010) Microencapsulation of islets with living cells using polyDNA-PEG-lipid conjugate. Bioconjug Chem 21 792-796... 

The fact that PEGylation of LEH is done by postinsertion necessitates the estimation of incorporated PEG-lipid in the outer layer of LEH. 

PEG is a widely used molecule as a component in pharmaceutical formulations. PEG is particularly useful thanks to its low cost and various simple synthetic methods (26). PEG-lipid has been developed as a means of stabilizing conventional liposomes. A lipid moiety has been linked to the large PEGylated head in order to anchor the molecule to the particles. Instead of shielding a direct layer of polymer PEG around the particle, which would be less stable, the idea is to favor hydrophobic interactions between the PEG-lipid and the particle bilayer lipids. This anchor had led to two conformations of the PEG on the particle surface commonly called mushroom and brush regimes (27), representing a more condensed or extended conformations... 

Figure 1 Commercially available PEG-lipids. Abbreviation PEG, poly (ethylene glycol).

The choice of commercially available PEG-lipids is ultimately quite reduced. The mainly reported ones are the anionic polyethylene glycol-phosphoethanolamine (PEG-PE) and the neutral PEG-ceramide (Fig. 1). 

Our laboratory mostly works with PEG-cholesterol. It is easily obtained in one step by addition of cholesteryl chloroformate and amino-methoxy-PEG (31). Introduction of a linker between the cholesterol and the PEG part would induce higher membrane fluidity and reduce more efficiently protein interactions as compared to PEG-cholesterol. A diaminobutane spacer was shown to improve significantly the sustained release of calcein from lipoplexes incubated in 30% serum (32). The spacer effect on bicatenar PEG-lipid has not been intensively studied because it can be expected that it would induce less effect on PEG-dioleoyl than on PEG-cholesterol, the lipidic anchor being predominant in the bilayer stabilization (Fig. 2). 

PEG-Lipid Bearing Anionic Charges Within the Spacer... 

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