Delivery of amphotericin B nanosuspensions to the brain and determination of activity against Balamuthia mandrillaris amebas

Received 9 June 2009; received in revised form 14 December 2009; accepted 18 December 2009. published online 08 January 2010.
Accepted Manuscript

Abstract

Amphotericin B was formulated as nanosuspensions to develop a nanoparticulate brain delivery system. Nanosuspensions were produced with different surfactant solutions by high pressure homogenization, and characterized by laser diffractometry and photon correlation spectroscopy. Before in vitro and in vivo testing, all nanosuspensions were investigated for protein adsorption by 2-dimensional polyacrylamide gel electrophoresis to predict brain targeting capacities. Selected nanosuspensions were tested for amebicidal activity against Balamuthia mandrillaris, an agent of lethal encephalitis. Our results indicate that polysorbate 80 (Tween 80) / sodium cholate-coated nanosuspensions significantly increased drug brain delivery and inhibited the parasite in vitro, though less in vivo.

Keywords: Nanosuspension, amphotericin B, 2-PE, in vitro in vivo correlation, high pressure homogenization, Balamuthia mandrillaris

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a Rijksuniversiteit Groningen, GUIDE, Farmaceutische Biologie, 9713 AV Groningen, the Netherlands

b Robert Koch Institute, Cellular Immunity Unit, 13353 Berlin, Germany

c Department of Pharmaceutical Technology, Biotechnology, Free University of Berlin, Kelchstraße 31, D-12169 Berlin, Germany

Corresponding author. Rijksuniversiteit Groningen, Farmaceutische Biologie, 9713 AV Groningen, The Netherlands. Tel.: +31 50 363 3299; fax: +31 50 363 3000.

1 Former address where work has been carried out.

PII: S1549-9634(10)00004-3

doi:10.1016/j.nano.2009.12.004