by Keyword: Half-antibodies
Urban, Patricia, Estelrich, Joan, Cortés, Alfred, Fernàndez-Busquets, X., (2011). A nanovector with complete discrimination for targeted delivery to Plasmodium falciparum-infected versus non-infected red blood cells in vitro Journal of Controlled Release 151, (2), 202-211
Current administration methods of antimalarial drugs deliver the free compound in the blood stream, where it can be unspecifically taken up by all cells, and not only by Plasmodium-infected red blood cells (pRBCs). Nanosized carriers have been receiving special attention with the aim of minimizing the side effects of malaria therapy by increasing drug bioavailability and selectivity. Liposome encapsulation has been assayed for the delivery of compounds against murine malaria, but there is a lack of cellular studies on the performance of targeted liposomes in specific cell recognition and on the efficacy of cargo delivery, and very little data on liposome-driven antimalarial drug targeting to human-infecting parasites. We have used fluorescence microscopy to assess in vitro the efficiency of liposomal nanocarriers for the targeted delivery of their contents to pRBCs. 200-nm liposomes loaded with quantum dots were covalently functionalized with oriented, specific half-antibodies against P. falciparum late form-infected pRBCs. In less than 90 min, liposomes dock to pRBC plasma membranes and release their cargo to the cell. 100.0% of late form-containing pRBCs and 0.0% of non-infected RBCs in P. falciparum cultures are recognized and permeated by the content of targeted immunoliposomes. Liposomes not functionalized with antibodies are also specifically directed to pRBCs, although with less affinity than immunoliposomes. In preliminary assays, the antimalarial drug chloroquine at a concentration of 2 nM, >= 10 times below its IC50 in solution, cleared 26.7 ± 1.8% of pRBCs when delivered inside targeted immunoliposomes.
JTD Keywords: Antimalarial chemotherapy, Chloroquine, Half-antibodies, Immunoliposomes, Malaria, Nanomedicine