PEG-Lipoplexes What More Is Needed

As of today, the insertion of PEG-lipid into lipoplexes helped in reducing the nonspecific interaction of lipoplexes with serum protein. However, the PEGy-lation did not totally reach its goal into improving lipoplex circulation time. 

New avenues could come from reacting small chemical entities with the remaining amines at the surface of the lipoplexes, to obtain completely neutralized DNA-loaded particles (57). Gain in circulation time was significant by this so-called postgrafting method. 

The second limitation, however, remains i.e., lipoplex stabilization, which prevents DNA release. A combination of solutions should be envisioned for further improvement. For instance, we could combine the postgrafting method with exchangeable PEG. We indeed combined the use of acid-sensitive PEG-lipid and the postgrafting method. Results tend to show an improved DNA release cumulated with higher circulation time (unpublished). However, the differences in tumor growth and vascularization render difficult the obten-tion of significant and reproducible results. 

Radler J, et al. Structure of DNA-cationic liposome complexes DNA intercalation in multilamellar membranes in distinct interhelical packing regimes. Science 1997 275 810. 

Ghirlando R, et al. DNA packaging induced by micellar aggregates a novel in vitro DNA condensation system. Biochemistry 1992 31 7110 Wagner K, et al. Direct evidence of the counterion release upon cationic lipid-DNA condensation. Langmuir 2000 16 303. 

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