Les, K.A., Mohamed-Ahmed, A.H.A., Balan, S., Choi, J.-W., Martin, D., Yardley, V., Powell, K., Godwin, A. and Brocchini, S. 2013. Poly(methacrylic acid) complexation of amphotericin B to treat neglected diseases. Polymer Chemistry. 5, pp. 1037-1048. https://doi.org/10.1039/c3py01051a
| Title | Poly(methacrylic acid) complexation of amphotericin B to treat neglected diseases |
|---|---|
| Type | Journal article |
| Authors | Les, K.A., Mohamed-Ahmed, A.H.A., Balan, S., Choi, J.-W., Martin, D., Yardley, V., Powell, K., Godwin, A. and Brocchini, S. |
| 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. |
| Journal | Polymer Chemistry |
| Journal citation | 5, pp. 1037-1048 |
| ISSN | 1759-9962 |
| Year | 2013 |
| Publisher | Royal Society of Chemistry |
| Digital Object Identifier (DOI) | https://doi.org/10.1039/c3py01051a |
| Publication dates | |
| Published | 2014 |
| Published online | 08 Oct 2013 |