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

Les, KA; Mohamed-Ahmed, AHA; Balan, S; Choi, J.-, W; Martin, D; Yardley, V; Powell, K; Godwin, A; Brocchini, S; (2014) Poly(methacrylic acid) complexation of amphotericin B to treat neglected diseases. Polymer chemistry, 5 (3). pp. 1037-1048. ISSN 1759-9954 DOI: https://doi.org/10.1039/c3py01051a

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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 similar to 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) mu M. 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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Leishmaniasis Group
Web of Science ID: 330154600044
URI: http://researchonline.lshtm.ac.uk/id/eprint/1620459


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