The role of apolipoprotein E in uptake of tovaquone into the brain in murine acute and reactivated toxoplasmosis

4^th International Conference on Medicinal Chemistry & Computer Aided Drug Designing

November 02-04, 2015 Atlanta, USA

Hend M Shubar1, Ildiko R Dunay1, Sabrina Lachenmaier1, Margitta Dathe2, Faris Nadiem Bushrab3, Rachmat Mauludin3, Rainer H M�¼ller3, Rudolf Fitzner1, Klaus Borner1 and Oliver Liesenfeld1

1Charit�© University, Germany 2Leibniz Institute for Molecular Pharmacology (FMP), Germany 3Free University of Berlin, Germany

Posters-Accepted Abstracts: Med chem

Abstract :

We investigated whether coating of Atovaquone Nanosuspensions (ANSs) with apolipoprotein E (apoE) peptides improves the uptake of atovaquone into the brain. The passage across the blood-brain barrier (BBB) of ANSs stabilized by polysorbate 80 (Tween 80), poloxamer 184 (P184), or poloxamer 338 (P338) and the same formulations coated with apoE peptides were analyzed in vitro and . Passage through a rat co-culture model of the BBB did not differ between individual atovaquone formulations, and the addition of apoE peptides did not enhance the transport. Following the induction of Toxoplasmic Encephalitis (TE) in mice, treatment with all atovaquone formulations reduced the number of parasites and inflammatory foci compared with untreated mice. Uptake of atovaquone into the brain did not depend on coating with apoE. Finally, incubation of apoE peptide�coated ANSs with brain endothelial cells for 30 min did result in the accumulation of nanoparticles on the cell surface but not in their uptake into the cells. In conclusion, ANSs coated with Tween 80 or poloxamers showed therapeutic efficacy in murine toxoplasmosis. ApoE and apoE-derived peptides do not induce the uptake of ANSs into the brain. Alternative mechanisms seem to be in operation, thereby mediating the passage of atovaquone across the BBB.

Biography :

Email: hshubar@hotmail.com