Lipoplexes phase structures

The use of responsive vectors highlights the multifaceted and complex nature of these cationic lipid vectors and the supramolecular structures they form with DNA. By varying composition, chain lengths, linkers, and various properties, the lipoplex phase can be tailored to improve gene delivery. The research featured in this chapter has shown how the use of responsive nonviral vectors can enhance endosomal escape of the lipoplex and release of DNA from the lipoplex system, subsequently affecting gene transfer. 

Given the need for intermixing of membrane lipids with lipoplex lipids as an important step in the sequence of transfection events, a set of recent findings, discussed below, takes on particular significance. These findings demonstrate that transfection efficiency closely correlates both with the cationic PC chain structure (Fig. 13a) [26] and with its effect on the lamellar-to-nonlamellar phase progressions observed in membrane lipids upon mixing with cationic PCs (Fig. 13, 26, and 27). 

Cellular anionic lipids have a twofold effect on DNA release from the lipo-plexes. They compensate the cationic lipid surface charge and eliminate the electrostatically driven DNA binding to the membrane interface, and they also disrupt the lipoplex structure and facilitate DNA departure into the solution by inducing formation of nonlamellar phases upon mixing with the lipoplex lipids. 

Koynova R, Wang L, MacDonald RC (2008) Cationic phospholipids forming cubic phases lipoplex structure and transfection efficiency. Mol Pharm 5 739-744... 

Figure 3 Schanatics of the packing parametas, Upid conformations, and supramolecular structures of lipoplexes (miceUar hexagonal phase. Hi lamellar, L inverted hexagonal, Hn). Lipids (red) and DNA (blue) are not drawn to scale.

Fig. 24.26 (a) Molecular Structures of 75 and DOPE, (b) SAXS diffiactogiams of 75/DOPE-pDNA lipoplexes at several various CxCL (Calixarene Cationic Lipid) molar fractions, (c) Mixed liposome from 75/DOPE at a = 0.5 and a lamellar La phase, derived thereof, (d) Cryo-TEM micrograph showing a general view of the 75/DOPE-pDNA lipoplex nanoaggregates at CxCL molar fractions of a = 0.2 [78]. (Reprinted from Ref. [78])... 

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