PEGylated phospholipids

Ashok, B., Rubinstein, I., Tsueshita, T. and Onyuksel, H. (2004), Effect of molecular mass and PEG chain length on the vasoreactivity of VIP and PACAPj 36 in PEGylated phospholipid micelles, Peptides, 25, 1253-1258. 

Figure 6.15 (Top) A scheme of noncovalently functionalized SWNTs by various PEGylated phospholipids, and SWNTs in mice tissues probed by ex vivo Raman spectroscopy after injection into mice, (a) Biodistribution of SWNT-/-2kPEG, SWNT-/-5kPEG, and SWNT-br-7kPEG, respectively, at 1 day postinjection measured by Raman spectroscopy. The SWNT concentrations in most organs are below detection hmit. (b) and (c) Evolution of the concentrations of SWNTs retained in the liver and spleen of mice over a period of 3 months. Compared with SWNT-/-2kPEG, much lower concentrations of retained SWNTs in the liver and spleen were observed for SWNT-/-5kPEG and SWNT-br-7kPEG.

Stability in plasma is an important requirement for IV emulsions as flocculated droplets may result in lung embolism. It was found that tocol-based emulsions stabilized by sodium deoxycholate/lecithins flocculated strongly when mixed with mouse, rat, and sheep plasma and serum, whereas soya oil-based emulsions with the same emulsifiers did not [123], It was hypothesized that this effect was caused by the adsorption of plasma proteins onto the tocol droplets (opsonization). Indeed, the steric stabilization of emulsions by incorporation of emulsifiers like poloxamer 188 or PEGylated phospholipids such as PEG5000PE proved to be effective in the stabilization of tocol-based emulsions in plasma. Conversely, in vitro studies were... 

Ashok, B. Arleth, L. Hjelm, R.P. Rubenstein, I. Onytlksel, H. In vitro characterisation of PEGylated phospholipid micelles for improved drug solubilisation effect of PEG chain length and PC incorporation. Journal of Pharmaceutical Sciences 2004, 93, 2476-2487. 

Self assembly using amphiphilic components to trap drug in solution within a hydrophobic or hydrophilic core has been explored for decades for the delivery of drugs. The most notable example is that of the liposome, which, however, suffered from low entrapment efficiency, leakage, and rapid clearance by the reticuloendothelial system of the liver. This rapid clearance was reduced by the use of PEGylated phospholipids to form of the so-called sterically stabilized or stealth liposomes. ... 

Phospholipids Soybean lecithin Egg lecithin Diolelyl phosphatidyl choline Distearoyl phosphatidyl glycerol PEGylated phospholipids Dimyristoyl phosphotidyl choline All routes... 

Insertion of PEG-lipid into conventional liposome phospholipid bilayer had substantially increased their circulation half-life. Pharmacokinetic of PEGylated liposome is clearly modified by the presence of the PEG-lipid extended circulation time was reported as reviewed (4). 

Moghimi, S. M., Hamad, I., Andresen, T. L., Jorgensen, K., and Szebeni, J. (2006), Methylation of the phosphate oxygen moiety of phospholipid-methoxy(polyethylene glycol) conjugate prevents PEGylated liposome-mediated complement activation and anaphylatoxin production, FASEB /., 20, 2591-2593. 

De Cuyper M, Crabbe A, Cocquyt J, Van der Meeren P, Martins F, Santana MHA (2004) PEGylation of phospholipids improves their intermembrane exchange rate. Phys Chem Chem Phys 6 1487-1492... 

The formation of liposomes [or better arsonoliposomes (ARSL)], composed solely of arsonolipids (Ars with R=lauric acid (C12) myristic acid (C14) palmitic acid (C16) and stearic acid (C18) (Fig. 1) have been used for ARSL construction), mixed or not with cholesterol (Choi) (plain ARSL), or composed of mixtures of Ars and phospholipids (as phosphatidylcholine [PC] or l,2-distearoyl- -glyceroyl-PC [DSPC]) and containing or not Choi (mixed ARSL), was not an easy task. Several liposome preparation techniques (thin-film hydration, sonication, reversed phase evaporation, etc.) were initially tested, but were not successful to form vesicles. Thereby a modification of the so called one step or bubble technique (8), in which the lipids (in powder form) are mixed at high temperature with the aqueous medium, for an extended period of time, was developed. This technique was successfiil for the preparation of arsonoliposomes (plain and mixed) (9). If followed by probe sonication, smaller vesicles (compared to those formed without any sonication [non-sonicated]) could be formed [sonicated ARSL] (9). Additionally, sonicated PEGylated ARSL (ARSL that contain polyethyleneglycol [PEG]-conjugated phospholipids in their lipid bilayers) were prepared by the same modified one-step technique followed by sonication (10). 

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