Noncovalent Connplexation of Amphotericin-B with Poly(alpha-glutamic acid)


Mohamed-Ahmed, AHA; Les, KA; Seifert, K; Croft, SL; Brocchini, S; (2013) Noncovalent Connplexation of Amphotericin-B with Poly(alpha-glutamic acid). Molecular pharmaceutics, 10 (3). pp. 940-950. ISSN 1543-8384 DOI: https://doi.org/10.1021/mp300339p

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Abstract

A noncovalent complex of amphotericin B (AmB) and poly(alpha-glutamic acid) (PGA) was prepared to develop a safe and stable formulation for the treatment of leishmaniasis. The loading of AmB in the complex was in the range of similar to 20-50%. AmB was in a highly aggregated state with an aggregation ratio often above 2.0. This complex (AmB-PGA) was shown to be stable and to have reduced toxicity to human red blood cells and KB cells compared to the parent compound; cell viability was not affected at an AmB concentration as high as 50 and 200 mu g/mL respectively. This AmB PGA complex retained AmB activity against intracellular Leishmania major amastigotes in the differentiated THP-1 cells with an EC50 of 0.07 +/- 0.03-0.08 +/- 0.01 mu g/mL, which is similar to Fungizone (EC50 of 0.06 +/- 0.01 mu g/mL). The in vitro antileishmanial activity of the complex against Leishmania donovani was retained after storage at 37 degrees C for 7 days in the form of a solution (EC50 of 0.27 +/- 0.03 to 0.35 +/- 0.04 mu g/mL) and for 30 days as a solid (EC50 of 0.41 +/- 0.07 to 0.63 +/- 0.25 mu g/mL). These encouraging results indicate that the AmB PGA complex has the potential for further development.

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: 315763500015
URI: http://researchonline.lshtm.ac.uk/id/eprint/856708

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