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

• Published in: Molecular pharmaceutics 2013-03, Vol.10 (3), p.940-950
• Main Authors: Mohamed-Ahmed, Abeer H. A, Les, Karolina A, Seifert, Karin, Croft, Simon L, Brocchini, Stephen
• Format: Article
• Language: English
• Subjects: Amphotericin B - chemistry; Amphotericin B - pharmacology; Amphotericin B - therapeutic use; Cell Line; Glutamic Acid - chemistry; Humans; Leishmania donovani - drug effects; Leishmania major - drug effects; Leishmania major - pathogenicity; Leishmaniasis - drug therapy; Solubility
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/mp300339p

A noncovalent complex of amphotericin B (AmB) and poly(α-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 ∼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 μg/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 μg/mL, which is similar to Fungizone (EC50 of 0.06 ± 0.01 μg/mL). The in vitro antileishmanial activity of the complex against Leishmania donovani was retained after storage at 37 °C for 7 days in the form of a solution (EC50 of 0.27 ± 0.03 to 0.35 ± 0.04 μg/mL) and for 30 days as a solid (EC50 of 0.41 ± 0.07 to 0.63 ± 0.25 μg/mL). These encouraging results indicate that the AmB–PGA complex has the potential for further development.