1: J Antimicrob Chemother. 2006 Feb;57(2):236-44. Epub 2005 Dec 16. 

Water-soluble amphotericin B-polyvinylpyrrolidone complexes with maintained
antifungal activity against Candida spp. and Aspergillus spp. and reduced
haemolytic and cytotoxic effects.

Charvalos E, Tzatzarakis MN, Van Bambeke F, Tulkens PM, Tsatsakis AM, Tzanakakis
GN, Mingeot-Leclercq MP.

School of Health and Caring Professions, Technological Educational Institution
of Athens, Pallikaridou 1, GR-122 10 Aegaleo, Greece.

OBJECTIVES: Poor solubility and toxicity severely hinder the clinical use of
amphotericin B (AmB), in spite of its attractive chemotherapeutic properties.
Water-soluble complexes of AmB and polyvinylpyrrolidone (AmB-PVP) could display
lower cytotoxicity while maintaining antifungal activity. METHODS: AmB-PVP [with
PVP of 10, 24 and 40 kDa (AC1, AC2 and AC4)] were compared with free AmB for (i)
activity against Candida spp. (five albicans; nine non-albicans) and Aspergillus
spp. (four strains), (ii) haemolysis of sheep red blood cells, and (iii) release
of lactate dehydrogenase from J774 macrophages [with further comparison with
free PVP and a liposomal formulation of amphotericin (AmBisome(R))]. RESULTS:
MICs and MFCs of AC1, AC2 and AC4 against Candida spp. and of AC2 and AC4
against Aspergillus spp. were similar to those of AmB (and even lower for some
Candida strains). Killing kinetics (24 h) were also similar. Haemolytic activity
of AC2 and AC4 was 2-fold lower than that of free AmB. Cytotoxicity of AC2
towards J774 macrophages was 8-fold lower, and that of AC4 5-fold lower than
that of AmB and not significantly different from that of AmBisome(R). The lower
cytotoxicity of AC2, AC4 was correlated with a lower cellular accumulation of
amphotericin. Spectroscopic analysis shows that the lower toxicity of AmB-PVP
was not owing to significant change in the monomeric/polymeric forms ratio of
the drug. CONCLUSIONS: AmB-PVP complexes compared favourably with AmB for
antifungal activity, were less haemolytic and cytotoxic than AmB, and show a
similar cytotoxicity profile to AmBisome(R).

PMID: 16361329 [PubMed - in process]