Solubilization and Delivery of Biomacromolecules

With the aim of designing a biologically inspired carrier in which the encapsulation and the delivery of DNA can be efficiently controlled, Amar-Yuli et al. have designed two lipid-based columnar hexagonal LLCs [58], which can accomplish two opposite roles while maintaining the same liquid crystalline symmetry. The first system was based on a nonionic lipid, such as monoolein, while the second system was modified by a low additional amount of the oleyl amine cationic surfactant. DNA was enzymatically treated to generate a broad distribution of contour lengths and diffusion characteristic times [58]. 

The impact of DNA confinement on these two columnar hexagonal stmctures was investigated by SAXS. Both the neat neutral and cationic LLC systems had a columnar hexagonal symmetry, the main difference being the reduced lattice of 49.8 A in the cationic system compared to the 55.5 A of the neutral formulation. This difference was interpreted to be the result of the kosmotropic effect of the oleyl amine, which, due to its charged nature, dehydrates the surfactant polar heads and reduces the LLC lattice [58]. 

A very different effect on the Hn lattice parameter was found when the DNA (1.4 wt% from the aqueous phase) was incorporated into the two systems. In the nonionic LLC system, the lattice parameter decreased from 55.5 to 50.8 A ( 0.5 A) in the presence of DNA. In contrast, in the cationic columnar phase the lattice parameter increased from 49.8 to 59.2 A. These effects can be rationalized by considering the negative charge of the DNA when added to the neutral formulation, DNA leads to a negative effective charge which dehydrates the lipid polar heads and reduces the lattice parameter on the other hand, when added to the cationic formulation, DNA partially neutralizes the overall positive charge, moderates the dehydration effect caused by the cationic surfactants and induces, at least partially, swelling of the lattice [58]. 

According to Amar-Yuli et al., these results indicated that the DNA is confined within the aqueous domains of the Hn cylinders [58], stabilized by hydrogen bonds with the water and/or GMO headgroups, and leading to an observable rupture of the H-bonds in the H-bond donor part of the GMO polar heads (OH) and a decrease in the frequency of the H-bond acceptor bands of the GMO polar heads (CO-0). The role of DNA in this case is thus consistent with moving away bound water from the interfacial region of the water channels. 

Examination of the second Hn system which contains the cationic surfactant oleyl amine shows very moderate changes upon incorporation of DNA in all the bands considered when compared to the nonionic mesophase. These data clearly suggested that in the presence of a cationic surfactant decorating the interface of the water channels, the interactions between the lipid polar heads and DNA change in nature, as the hydrogen bonding of D2O and the GMO polar heads is mostly unaffected by the presence of DNA. It was inferred that the DNA is confined in the water channels also in the cationic Hn mesophases, and electrostatically bound to their surfaces [58]. 

---