Abstract
The adaptation of existing antimalarial nanocarriers to new Plasmodium stages, drugs, targeting molecules, or encapsulating structures is a strategy that can provide new nanotechnology-based, cost-efficient therapies against malaria. We have explored the modification of different liposome prototypes that had been developed in our group for the targeted delivery of antimalarial drugs to Plasmodium-infected red blood cells (pRBCs). These new models include: (i) immunoliposome-mediated release of new lipid-based antimalarials; (ii) liposomes targeted to pRBCs with covalently linked heparin to reduce anticoagulation risks; (iii) adaptation of heparin to pRBC targeting of chitosan nanoparticles; (iv) use of heparin for the targeting of Plasmodium stages in the mosquito vector; and (v) use of the non-anticoagulant glycosaminoglycan chondroitin 4-sulfate as a heparin surrogate for pRBC targeting. The results presented indicate that the tuning of existing nanovessels to new malaria-related targets is a valid low-cost alternative to the de novo development of targeted nanosystems.
Highlights
Chondroitin 4-sulfate (CSA) has been found to act as a receptor for Plasmodium-infected red blood cells (RBCs) (pRBCs) binding in the microvasculature and the placenta,[10] and adhesion of pRBCs to placental CSA has been linked to the severe disease outcome of pregnancy-associated malaria.[11] pRBC adhesion to the endothelium of postcapillary venules is mediated by the parasite-derived antigen Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1),[12] whereas CSA has been identified as the main receptor for PfEMP1 attachment to placental cells.[10,13]
The data presented here allow us to propose several combinations of nanovector parts that could be adapted to new antimalarial strategies: (i) liposomes formulated with antimalarial lipids and targeted with covalently bound heparin could carry the active agents in their bilayer membranes with little leaking before reaching their target site and with low hemorrhagic risk
Liposomes have a long record of proven biocompatibility and their lipid formulation can be adapted to obtain either fast or slow drug release,[8] which makes them adaptable to carrying antimalarial drugs with diverse pharmacokinetic profiles. (ii) Since resistance of Plasmodium to heparin has not been shown so far,[55] heparin-based targeting will predictably be more long-lasting than pRBC recognition relying on antibodies, which typically are raised against highly variable exposed antigens whose expression is constantly modified by successive generations of the parasite.[56]
Summary
One of the limitations of liposomes as carriers for drug delivery to Plasmodium-infected RBCs (pRBCs) is that because of the lack of endocytic processes in these cells, a relatively fluid liposome lipid bilayer is required to favor fusion events with the pRBC plasma membrane. As a result, these liposomes are leaky for small drugs encapsulated in their lumen,[8] and when membrane fusion occurs, only a relatively small fraction of the originally contained drug is delivered into the cell. A question that remains open is whether the heparin-mediated targeting of liposomes to pRBCs could be extended to other glycosaminoglycans, to different Plasmodium stages, and to new nanoparticle types
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Nanomedicine: Nanotechnology, Biology and Medicine
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
