PEGylated lipoplexes

As expected, acid-labile PEG did not increase the circulation time of the lipoplexes as compared to PEGylated lipoplexes but allowed for the same level to be reached, indicating the stability of the acid-sensitive PEG-lipid moiety in the blood. 

Figure 7 Continued on next page) Comparison of the biodistribution of PEGylated lipoplexes in vivo. Abbreviation. PEG, poly(ethylene glycol).

Mignet N, Richard C, Seguin J, Largeau C, Bessodes M, Scherman D (2008) Anionic pH-sensitive pegylated lipoplexes to deliver DNA to the tumors. Int J Pharm 361(1-2) 194-201... 

As described above, lipoplex PEGylation limits the formation of aggregates and zeta potential changes in serum. 

To reach this goal, we have designed tunable anionic pH sensitive lipoplexes. These complexes are anionic at physiological pH and pegylated to improve their circulation time, as compared to cationic lipoplexes (22). Moreover, they become cationic at pH under 6, in order to promote efficient tumor cell internalization, since it is widely recognized that extracellular pH is acidic in ischemic tumor tissue (see Scheme 1). 

Sanders NN, De Smedt SC, Cheng SH, Demeester J. Pegylated GL67 lipoplexes retain their gene transfection activity after exposure to components of CF mucus. Gene Ther 2002, 9, 363-371. 

Block polymers of PEG-polycation (A-B) or PEG-polycation-PEG (A- B-A) have been used to condense a nucleic acid dmg, to form PEGylated micelles, with the water-insoluble nucleic add-polycation electrostatic complexes (polyplexes) forming the core of the PEGylated polymeric micelle. In the 2000s, a number of companies (e.g., Alnylam, Roche, Merck, and Galando) have been involved in clinical trials for delivery of siRNA from similar lipoplexes and polyplexes. ... 

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