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Issue 3, 2014
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Poly(methacrylic acid) complexation of amphotericin B to treat neglected diseases

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Abstract

Amphotericin B (AmB) is used to treat a neglected disease called visceral leishmaniasis (VL). We hypothesised that direct non-covalent association of AmB with poly(methacrylic acid) (PMAA) would replicate many of the properties of liposomal AmB (AmB-L), which is more efficacious than micellar AmB (AmB-D). Water-soluble AmB–PMAA complexes with AmB loadings ranging from ∼20 to 45% were reproducibly prepared. The AmB in the PMAA complex displayed similar aggregation properties to the AmB within AmB-L. The AmB–PMAA complex displayed low heamolytic properties while maintaining in vitro activity against Leishmania donovani amastigotes with no macrophage toxicity observed at an IC50 of 0.043 (±0.003) μM. AmB–PMAA complexes were well tolerated in vivo at a total dose of 6 mg kg−1 and both the complex (2.2 mg kg−1 AmB) and AmB-L (2.5 mg kg−1 AmB) achieved greater than 90% parasite inhibition in vivo after a single dose against L. donovani in HU3 infected BALB/c mice.

Graphical abstract: Poly(methacrylic acid) complexation of amphotericin B to treat neglected diseases

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Publication details

The article was received on 04 Aug 2013, accepted on 05 Oct 2013 and first published on 08 Oct 2013


Article type: Paper
DOI: 10.1039/C3PY01051A
Polym. Chem., 2014,5, 1037-1048

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    Poly(methacrylic acid) complexation of amphotericin B to treat neglected diseases

    K. A. Les, A. H. A. Mohamed-Ahmed, S. Balan, J. Choi, D. Martin, V. Yardley, K. Powell, A. Godwin and S. Brocchini, Polym. Chem., 2014, 5, 1037
    DOI: 10.1039/C3PY01051A

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