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

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.