Histidine-Based Lipopeptides Enhance Cleavage of Nucleic Acids: Interactions with DNA and Hydrolytic Properties.

Interaction studies and cleavage activity experiments were carried out between plasmid DNA and a series of histidine-based lipopeptides. Specific fluorescent probes (ethidium bromide, Hoechst 33342, and pyrene) were used to monitor intercalation, minor groove binding, and self-assembly of lipopeptides, respectively. Association between DNA and lipopeptides was thus evidenced, highlighting the importance of both histidine and hydrophobic tail in the interaction process. DNA cleavage in the presence of lipopeptides was then detected by gel electrophoresis and quantified, showing the importance of histidine and the involvement of its side-chain imidazole in the hydrolysis mechanism. These systems could then be developed as synthetic nucleases while raising concern of introducing histidine in the design of lipopeptide-based transfection vectors.

Layer-by-layer coating of degradable microgels for pulsed drug delivery.

Recently, we reported on "self-rupturing" microcapsules which consist of a biodegradable dextran-based microgel surrounded by a polyelectrolyte membrane. Degradation of the microgel increases the swelling pressure in the microcapsules which, when sufficiently high, ruptures the surrounding polyelectrolyte membrane. The membrane surrounding the microgels is deposited using the layer-by-layer (LbL) technique, which is based on the alternate adsorption of oppositely charged polyelectrolytes onto a charged substrate. In this paper, we characterize with confocal microscopy, electrophoretic mobility, scanning electron microscopy and atomic force microscopy in detail the deposition and the properties of the LbL coatings on the dextran microgels. We show that by fine-tuning the properties of both the microgel core and the LbL membrane the swelling pressure which is evoked by the degradation of the microgel is indeed able to rupture the surrounding LbL membrane. Further, we show that the application of an LbL coating on the surface of the microgels dramatically lowers the burst release from the microcapsules and results in massive release at the time the microcapsules rupture.