In vitro inhibition of fungal activity by macrophage-mediated sequestration and release of encapsulated amphotericin B nanosupension in red blood cells.
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.
Staedtke
V
V
Center of Tumor Medicine, Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin, Berlin Charitéplatz 1, 10117 Berlin, Germany.
Brähler
M
M
Müller
A
A
Georgieva
R
R
Bauer
S
S
Sternberg
N
N
Voigt
A
A
Lemke
A
A
Keck
C
C
Möschwitzer
J
J
Bäumler
H
H
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
D000935:Antifungal Agents; D013535:Suspensions; D000666:Amphotericin B