PEG-lipid conjugates

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... 

Song L, et al. Characterization of the inhibitory effect of PEG-lipid conjugates on the intracellular delivery of plasmid and antisense DNA mediated by cationic lipid liposomes. Biochim Biophys Acta 2002 1558 1. 

Lipid moieties coupled to polyethylene glycol (PEG) have been used to increase the blood circulation time of lipoplexes (Fig. 32). The PEG-lipid conjugates such as DOPE-PEG, Chol-PEG, ceramides-PEG and their derivatives are then coformulated with the cationic lipid, helper lipid, and DNA. This results in coating the surface of the lipoplexes with PEG and preventing undesired association with plasma proteins or circulating cells (stealth liposomes). Recently, a-tocopheryl PEG-succinate (TPGS) was also used in gene delivery formulations because of its ability to confer not only a stealth property but also antioxidant and absorption enhancer properties [129]. 

The impact of the conventional PEG-lipids on the acid-induced destabilization of pH-sensitive liposomes is possibly due to two main reasons on one hand as the protonation of DOPE head group is the basis of acid-driven transition, it might be hindered by ionization of phosphate or carbamate linkages introduced by the incorporation of the conventional PEG-lipids (25). On the other hand, as the DOPE is a cone-shaped lipid, the incorporation of PEG-lipid conjugates that have a complementary inverted cone shape that can stabilize the lamellar phase even at low pH of the medium (32, 33). 

These results indicate that the decrease in the PEG content on the MPEG-SHz liposomes is attributable to the unstable bonding between PEG and the liposome surface, but not to the physical extraction of the PEG-lipid conjugate from the liposomal membrane. 

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... 

Carrion C, Domingo JC, de Madariaga MA. Preparation of long-circulating immunoliposomes using PEG-cholesterol conjugates effect of the spacer arm between PEG and cholesterol on liposomal characteristics. Chem Phys Lipids 2001 113 97. 

Guo X, Szoka E. Steric stabilization of Fusogenic Liposomes by a low-pH sensitive PEG-diortho ester-lipid conjugate. Bioconj Chem 2001 12 291. 

Guo, X., and Szoka, F. C., Jr. Steric stabilization of fusogenic liposomes by a low-pH sensitive PEG-diortho ester—lipid conjugate. Bioconjug. Chem. 12(2) 291—300. 2001. 

Water-soluble polymers conjugated with lipids can form micelles in aqueous media, and they can be used for the solubilization and enhanced delivery of a variety of sparingly soluble drugs. The basic structures of these polymer-lipid conjugates are similar to amphiphilic block copolymers except for the fact that hydrophobic parts are composed of lipids instead of hydro-phobic polymers. For example, a hydrophilic PEG block is conjugated with phosphatidylethanolamine. ... 

We typically use 2% PEG-lipids (PEG molecular weight 2000) in our anti-body-conjugated formulations in order to control aggregation but still retain reasonable binding and coupling efficiency. 

Fig. 4. Aggregation reactions associated with different classes of antibody-liposome conjugates. (A) Antibody-liposome conjugates may react further with other liposomes to form aggregates. (B) The presence of PEG-lipids prevents these crosslinking reactions through steric hindrance. (C) Individual proteins may penetrate the PEG cloud to react with the liposome surface. (D) Antibodies tethered on the distal end of PEG may react with the distal ends of PEG molecules on a second liposome, resulting in crosslinking.

It should be noted that in our experience the liposome conjugation efficiency varies for different MAbs therefore, it is necessary to perform preliminary experiments to determine optimal initial antibody/lipid ratios. Other factors affecting conjugation efficiency include maleimide concentration, degree of thiolation, presence of PEG-lipids, and initial reagent concentration. 

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