Title
PLGA nanoparticles and nanosuspensions with amphotericin B : potent **in vitro** and **in vivo** alternatives to Fungizone® and AmBisome®PLGA nanoparticles and nanosuspensions with amphotericin B : potent **in vitro** and **in vivo** alternatives to Fungizone® and AmBisome®
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Research group
Laboratory of Pharmaceutical Technology and Biopharmacy
Laboratory for Microbiology, Parasitology and Hygiene (LMPH)
Department of Biomedical Sciences
Publication type
article
Publication
Amsterdam,
Subject
Chemistry
Biology
Pharmacology. Therapy
Source (journal)
Journal of controlled release. - Amsterdam
Volume/pages
161(2012):3, p. 795-803
ISSN
0168-3659
ISI
000308077000010
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
This paper describes the development of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) and nanosuspensions with the polyene antibiotic amphotericin B (AmB). The nanoformulations were prepared using nanoprecipitation and were characterised with respect to size, zeta potential, morphology, drug crystallinity and content. Standard in vitro sensitivity tests were performed on MRC-5 cells, red blood cells, Leishmania infantum promastigotes and intracellular amastigotes and the fungal species Candida albicans, Aspergillus fumigatus and Trichophyton rubrum. The in vivo efficacy was assessed and compared to that of Fungizone® and AmBisome® in the acute A. fumigatus mouse model at a dose of 2.5 and 5.0 mg/kg AmB equivalents. The developed AmB nanoformulations were equivalently or more effective against the different Leishmania stages and axenic fungi in comparison with the free drug. The in vitro biological activity, and especially hemolytic activity, clearly depended on the preparation parameters of the different nanoformulations. Further, we demonstrated that the superior in vitro antifungal activity could be extrapolated to the in vivo situation. At equivalent dose, the optimal AmB-loaded PLGA NP was about two times and the AmB nanosuspension about four times more efficacious in reducing the total burden than AmBisome®. The developed AmB nanomedicines could represent potent and cost-effective alternatives to Fungizone® and AmBisome®.
E-info
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