Publications by authors named "Jacques Bolard"

Fluorescence has recently been applied to the analysis of the molecular organization state of the polyene antibiotic amphotericin B (AmB) in solution or in lipid membranes. The polyene chain of AmB monomer gives rise to two fluorescence emissions; S(1)(2(1)A(g)) → S(0)(1(1)A(g)) between 500 and 700 nm, S(2)(1(1)B(u)) → S(0)(1(1)A(g)) between 400 and 500 nm. However, Raman scattering might interfere with the S(2) → S(0) emission fluorescence due to the weak fluorescence quantum yield and close proximity to the exciting lines.

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Objectives: Based on the assertion that fluorescence spectroscopy detects dimers of the polyene antibiotic amphotericin B (AmB), this technique was recently proposed to analyse the interaction of the drug with cell membranes. However, contradictory results indicate that this 'dimeric' fluorescence might actually originate from polyene impurities. We used a highly purified AmB to challenge this last proposal.

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The positively charged polyene molecule amphotericin B 3-dimethylaminopropylamide (AMA) is an efficient agent for the delivery of antisense oligodeoxyribonucleotides (ODN) into target cells. In the present study, bilayer lipid membrane (BLM) conductance, elasticity modulus perpendicular to the membrane plane, surface potential and electrical capacitance were measured by conductance and electrostriction methods in the presence of AMA, pure or complexed to 20-mer single stranded ODN at different ratios. Pure AMA did not induce changes in conductance of cholesterol-containing BLM, but did induce an increase in elasticity modulus and surface potential.

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Flow cytometry light scattering was used to monitor size increase of Candida albicans (isolate ATCC 10231) cells in the presence or absence of the antifungal drug amphotericin B (AmB). This non-invasive and descriptive method allowed for the differentiation of dead and dormant sub-populations of cells. When inoculated into a growth medium without AmB, a progressive increase in light scattering was observed over a period of approximately 4 h, but without proliferation of the yeast.

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The toxicity of the antifungal polyene antibiotic amphotericin B (AMB) has been related to its low solubility, more specifically to a self-associated form termed toxic aggregate. In addition, AMB in aqueous medium gives rise to concentration, ionic strength, and time-dependent polydisperse systems. For this reason different approaches, including the use of several lipid aggregates, have been used in attempts to improve the drug's solubility and increase its therapeutic index.

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Article Synopsis
  • MFAME, a derivative of Amphotericin B, maintains the same antifungal effectiveness as AMB but has significantly lower toxicity to mammalian cells.
  • A comparison of AMB and MFAME's interactions with fungal, mammalian, and bacterial cells shows that their binding to cell membranes is similar across all types.
  • The reduced toxicity of MFAME arises from its lower ability to disrupt mammalian cell membranes compared to AMB, rather than differences in how strongly they bind to cells.
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This chapter provides a basic overview of most of the oligonucleotide delivery systems available for an in vitro use. Two major classes are described: systems that act through an endocytosis process (e.g.

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Aim: Heat treatment of deoxycholate-amphotericin B (AmB-DOC) leads to a therapeutically interesting supramolecular rearrangement (h-AmB-DOC); this reformulation improves the therapeutic index of AmB-DOC by reducing amphotericin B (AmB) toxicity in mammalian cell lines from 3- to 10-fold. Its activity in experimentally induced fungal infection in mice remains unchanged compared with AmB-DOC, whereas its activity is 2.5 times higher in Leishmania donovani-infected mice.

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