ImmunoPEGliposomes for the targeted delivery of novel lipophilic drugs to red blood cells in a falciparum malaria murine model
Open accessAbstract
Most drugs currently entering the clinical pipeline for severe malaria therapeutics are of lipophilic nature, with a relatively poor solubility in plasma and large biodistribution volumes. Low amounts of these compounds do consequently accumulate in circulating Plasmodium-infected red blood cells, exhibiting limited antiparasitic activity. These drawbacks can in principle be satisfactorily dealt with by stably encapsulating drugs in targeted nanocarriers. Here this approach has been adapted for its use in immunocompetent mice infected by the Plasmodium yoelii 17XL lethal strain, selected as a model for human blood infections by Plasmodium falciparum. Using immunoliposomes targeted against a surface protein characteristic of the murine erythroid lineage, the protocol has been applied to two novel antimalarial lipophilic drug candidates, an aminoquinoline and an aminoalcohol. Large encapsulation yields of >90% were obtained using a citrate-buffered pH gradient method and the resulting immunoliposomes reached in vivo erythrocyte targeting and retention efficacies of >80%. In P. yoelii-infected mice, the immunoliposomized aminoquinoline succeeded in decreasing blood parasitemia from severe to uncomplicated malaria parasite densities (i.e. from ≥25% to ca. 5%), whereas the same amount of drug encapsulated in non-targeted liposomes had no significant effect on parasite growth. Pharmacokinetic analysis indicated that this good performance was obtained with a rapid clearance of immunoliposomes from the circulation (blood half-life of ca. 2 h), suggesting a potential for improvement of the proposed model.
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Blood stage parasites are the main therapeutic target, and researchers are developing various approaches to target antimalarials to infected RBCs.
“Given that blood stage parasites are the main therapeutic target, researchers are developing various approaches to target antimalarials to infected RBCs 105-107 , thereby maximizing their therapeutic window.”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [106]
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Clark, N. F., Heimann, K., Vasilev, K. A., Bright, R., & Mangoni, A. A. (2026) · MedScience · doi:10.1007/s11684-026-1214-2
- Authors
- Moles, E., Galiano, S., Gomes, A., Quiliano, M., Teixeira, C., Aldana, I., Gomes, P., & Fernàndez-Busquets, X.
- Affiliations
- Barcelona Institute of Science and Technology (ES)
- Universidad de Navarra (ES)
- Universidade do Porto (PT)
- Corresponding author
- Moles, Ernest
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 145
- Pages
- 178-191
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2746705829
- Cited by
- 41
- References
- 55
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 6 · 2023: 4 · 2022: 2 · 2021: 7 · 2020: 6 · 2019: 7 · 2018: 5
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (acceptedVersion, other-oa)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by-nc-nd)
- Funders
- Ministerio de Economía y Competitividad (BIO2014-52872-R)
- Generalitat de Catalunya (2014-SGR-938)
- Universidad de Navarra
- CAN Foundation (70391)
- Instituto de Salud Tropical of the Universidad de Navarra
- Fundação para a Ciência e Tecnologia (UID/QUI/50006/2013, PD/BD/135073/2017)
- Comissão de Coordenação e Desenvolvimento Regional do Norte
- Programa Nacional de Innovación para la competitividad y productividad (065-FINCYT-BDE-2014)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- immunoliposomes, targeted drug delivery, Plasmodium yoelii 17XL, falciparum malaria, aminoquinolines, amino alcohols, pharmacokinetics, liposome clearance, nanocarriers
- MeSH terms
- Animals, Antibodies, Monoclonal, Antimalarials, Disease Models, Animal, Erythrocytes, Humans, Immunocompetence, Lipids, Liposomes, Mice, Inbred BALB C, Plasmodium falciparum, Polyethylene Glycols, Drug Delivery Systems, Malaria, Falciparum, Inhibitory Concentration 50, Maximum Tolerated Dose
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