Polyoxyethylene glycol polymers Sample Clauses

Polyoxyethylene glycol polymers. Polyoxyethylene glycol is a flexible hydrophilic polymer that extends approximately 3-5 nm from liposomal surfaces depending on the length and concentration (Vp, T., 1994). In addition it is non-ionic, water-soluble and is usually associated with phosphatidylethanolamines such as DSPE or DMPE serving as a bilayer anchor (Xxxx, M.S. et al., 1998). The addition of a polymer such as polyethylene glycol is known to improve the stability of nucleic acid complexes and increase their in vivo half-life (Xxxxxx, X. et al., 2004, Xxxxxxxxx, X. et al., 2010). When they are added to a conventional liposome they form a steric barrier on the surface of the complexes, which inhibits opsonisation and thus prolongs the circulation time of the liposomes in the blood (Xxxxxx, P. et al., 2000). These pegylated-lipid/pDNA complexes have also been shown to be stable and to protect DNA from nuclease degradation in the plasma (Xxxxxx, P. et al., 2000, Xxxx, L.Y. et al., 2002). In addition incorporation of a PEG lipid prevents aggregation during storage and it preserves their transfection activity (Xxx, X.X. xx al., 2003). Xxxxxxx et al (2002) showed that exposure of the conventional DOTAP:DOPE lipoplexes to cystic fibrosis mucus components (albumin, mucin, DNA and phospholipids) reduced their transfection activity in vitro and this was associated with lipoplex aggregation, but it did not affect the transfection efficiency or activity of the pegylated complexes. However the hydrophilic nature of pegylated-lipid may present a disadvantage in terms of transfection efficiency as it can reduce cell binding and membrane fusion (Xxxxxx, P. et al., 2000, Xxxx, L.Y. et al., 2002). However, it has been shown that the reduction in transfection caused by pegylated- lipid is concentration dependent, and efficient transfection can still occur with complexes prepared with less than 2 mol% of pegylated-lipid. In addition, the length of the PEG chain is also a factor and it was shown that by using short length chains there was less inhibition of transfection (Xxxxxx, P. et al., 2000).
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