title: In vitro inhibition of fungal activity by macrophage-mediated sequestration and release of encapsulated amphotericin B nanosupension in red blood cells.
abstract: The efficacy of antifungal treatment has been diminished by the biodistribution limitations of amphotericin B (AmB) due to its pharmacological profile, as well as the severe side effects it causes. A cellular drug-delivery system, which incorporates human erythrocytes (RBCs) loaded with an AmB nanosuspension (AmB-NS), is developed in order to improve antifungal treatment. AmB-NS encapsulation in RBCs is achieved by using hypotonic hemolysis, leading to intracellular AmB amounts of 3.81 +/- 0.47 pg RBC(-1) and an entrapment efficacy of 15-18%. Upon phagocytosis of AmB-NS-RBCs, leukocytes show a slow AmB release over ten days, and no alteration in cell viability. This results in an immediate, permanent inhibition of intra- and extracellular fungal activity. AmB-NS-RBC-leukocyte-mediated delivery of AmB is efficient in amounts 1000 times lower than the toxic dose. This drug-delivery method is effective for the transport of water-insoluble substances, such as AmB, and this warrants consideration for further testing.
authors.affiliation: Center of Tumor Medicine, Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin, Berlin Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Staedtke
authors.forename: M
authors.initials: M
authors.lastname: Brähler
authors.forename: A
authors.initials: A
authors.lastname: Müller
authors.forename: R
authors.initials: R
authors.lastname: Georgieva
authors.forename: S
authors.initials: S
authors.lastname: Bauer
authors.forename: N
authors.initials: N
authors.lastname: Sternberg
authors.forename: A
authors.initials: A
authors.lastname: Voigt
authors.forename: A
authors.initials: A
authors.lastname: Lemke
authors.forename: C
authors.initials: C
authors.lastname: Keck
authors.forename: J
authors.initials: J
authors.lastname: Möschwitzer
authors.forename: H
authors.initials: H
authors.lastname: Bäumler
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage* / Q000737:chemistry*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry; D002176:Candida albicans / Q000187:drug effects*; D002478:Cells, Cultured; D004339:Drug Compounding; D004912:Erythrocytes / Q000166:cytology* / Q000187:drug effects / Q000382:microbiology*; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008422:Materials Testing; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry*; D013535:Suspensions
chemical_list: D000935:Antifungal Agents; D013535:Suspensions; D000666:Amphotericin B