Nanosuspensions for the formulation of aphidicolin to improve drug targeting effects against leishmania infected macrophages.
A series of labdans and their derivatives have been identified as novel potential antileishmanial drugs using an in vitro test system against extracellular promastigotes and intracellular amastigotes of Leishmania donovani in murine macrophages (Kayser, O., Kiderlen, A.F., 1998. In vitro activity of leishmanicidal labdanes and related compounds. Proceedings of the Ninth International Congress of Parasitology, Monduzi Editore, Bologna, 925-929). Of these compounds, aphidicolin, a tetradecanhydro-3,9-dihydroxy-4,11b-dimethyl-8, 11a-methano-11aH-cyclo-hepta[a]naphthalin-4,9-dimethanol+ ++ (Fig. 1), was shown to be highly active at concentrations in the microgram range (EC(50) = 0.16 microg/ml). To improve drug targeting effects aphidicolin was formulated as nanosuspension and retested for its enhanced activity (EC(50) = 0.003 microg/ml).
Kayser
O
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Institut für Pharmazie, Pharmazeutische Technologie, Biopharmazie und Biotechnologie, Freie Universität Berlin, Kelchstrasse 31, D-12169, Berlin, Germany. kayser@zedat.fu-berlin.de
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology; D016590:Aphidicolin / Q000737:chemistry / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000469:parasitology; D004121:Dimethyl Sulfoxide / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects* / Q000254:growth & development; D008264:Macrophages / Q000187:drug effects* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D011136:Polysorbates / Q000737:chemistry / Q000494:pharmacology; D013535:Suspensions / Q000737:chemistry / Q000494:pharmacology*
D000981:Antiprotozoal Agents; D011136:Polysorbates; D013535:Suspensions; D016590:Aphidicolin; D004121:Dimethyl Sulfoxide