A multilamellar nanoliposome stabilized by interlayer hydrogen bonds increases antimalarial drug efficacy.

Lipid particles for drug delivery can be modified to create multilayer vesicles with higher stability and improved cargo interaction. Here, we used lipids capable of forming hydrogen bonds instead of covalent bonds and designed stable vesicles-inside-vesicles with a high capacity of entrapping antimalarial drugs such as chloroquine (hydrophilic) and Artemisinin (lipophilic). In vitro treatment of the drug-sensitive P. falciparum strain NF54 showed that encapsulated drugs resulted in 72% and 60% lower IC50 values for each drug, respectively. Fluorochrome-labeling of a cargo-peptide or of membrane-resident lipids indicated that vesicles interacted more specifically with parasite-infected erythrocytes than with normal red blood cells. Accordingly, vesicle-confined chloroquine was able to elicit a stronger antiparasitic effect than free chloroquine in a lethal murine model of infection. Being permissive not only to small molecules but also to larger peptides, hydrogen-bond linked multilamellar liposomes are a very promising approach for enhanced drug delivery.

DNA-Loaded Cationic Liposomes Efficiently Function as a Vaccine against Malarial Proteins.

The delivery of antigens as DNA vaccines is an efficient alternative to induce immune responses against antigens, which are difficult to produce in recombinant form. However, the delivery of naked DNA is ineffective or relies on sophisticated ballistic devices. Here, we show a combination of liposome application and naked DNA vaccine that successfully overcomes these problems. Upon entrapment of plasmids encoding different antigens in cationic particles, transfection efficiencies similar to commercial kits were achieved in in vitro cell cultures. The liposome-based approach provided strong humoral responses against three malarial antigens, namely the Circumsporozoite protein and the C terminus of merozoite surface protein 1 from Plasmodium vivax (titers 104 or 103-104, respectively) and P. falciparum Rhoptry antigen 5 from Plasmodium falciparum (titers 103-104). When employed in P. falciparum growth-inhibition assays, antibodies demonstrated consistent reinvasion-blocking activities that were dose dependent. Liposome-formulated DNA vaccines may prove useful when targets cannot be produced as recombinant proteins and when conformation-dependent and highly specific antibodies are mandatory.