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

文献情報

出版日 2013-10-08

DOI 10.1039/C3PY01051A

インパクトファクター 5.582

著者

Ji-won Choi, Denis Martin, Vanessa Yardley, Keith Powell, Antony Godwin

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要旨

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.

掲載誌

Polymer Chemistry

CiteScore: 8.6

自己引用率: 7.3%

年間論文数: 457

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

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