According to a new study, when two drugs with different properties are encapsulated into nanovesicles enclosed by antibodies, their delivery and efficacy can be considerably improved.
The study was headed by Xavier Fernández Busquets, director of the joint Nanomalaria unit at the Institute for Bioengineering of Catalonia (IBEC) and also by the Barcelona Institute for Global Health (ISGlobal)—an institution supported by “la Caixa.”
Integrating two drugs that work through diverse mechanisms is one of the most efficient methods presently used to treat malaria. Conversely, differences in the physicochemical properties of drugs, like half-life, solubility, etc., usually have an impact on treatment efficacy.
In order to overcome this barrier, Fernández Busquets and his group have created a nanovector—comprising liposomes or tiny spheres—that can concurrently transport water-soluble (hydrophilic) compounds and lipid-soluble (lipophylic) compounds.
By encapsulating both drugs in the same nanovector, we make sure that both will persist for the same time in the organism.
Xavier Fernández-Busquets, Director of the Joint Nanomalaria Unit, Institute for Bioengineering of Catalonia
As proof of concept, the scientists introduced pyronaridine, a water-soluble drug, in the liposome lumen and atovaquone, a lipid-soluble drug, in its membrane. They also enclosed the liposome with an antibody that detects gametocytes (the sexual phase of the parasite that is accountable for host-to-host transmission) and a protein which is expressed by red blood cells (whether they are infected or not). Hence, the term immunoliposome.
The outcomes demonstrated that when both drugs are encapsulated, they prevented the in-vitro growth of parasite at concentrations that did not have any impact when utilized as free drugs.
The antibodies cause the liposomes to bind quickly to the target cells and deliver the drug efficiently. In the near future, this method could be used for treating severe cases of malaria in patients who are admitted in hospitals, where it is feasible to administer the liposomes intravenously, claimed the authors.
The difficulty lies in creating nanovectors that are sufficient for oral administration to treat non-complicated malaria—a series of work that is presently being explored by the researchers.
“Current treatments target mostly the asexual phases of the parasite. This new strategy would also target the sexual phase or gametocyte, the only phase that can be transmitted from humans to mosquitoes, and would thereby contribute to reducing the emergence and spread of antimalarial resistance,” added the researcher.