TY - JOUR
T1 - In vitro inhibition of fungal activity by macrophagemediated sequestration and release of encapsulated amphotericin B nanosupension in red blood cells
AU - Staedtke, V.
AU - Brähler, M.
AU - Müller, A.
AU - Georgieva, R.
AU - Bauer, S.
AU - Sternberg, N.
AU - Voigt, A.
AU - Lemke, A.
AU - Keck, C.
AU - Möschwitzer, J.
AU - Bäumler, H.
PY - 2010/1/4
Y1 - 2010/1/4
N2 - 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 ±0.47pg 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-NSRBC-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.
AB - 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 ±0.47pg 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-NSRBC-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.
KW - Amphotericin B, drug carriers, erythrocytes, macrophages, nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=73949146977&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=73949146977&partnerID=8YFLogxK
U2 - 10.1002/smll.200900919
DO - 10.1002/smll.200900919
M3 - Article
C2 - 19882684
AN - SCOPUS:73949146977
SN - 1613-6810
VL - 6
SP - 96
EP - 103
JO - Small
JF - Small
IS - 1
ER -