title: Noncovalent complexation of amphotericin-B with Poly(α-glutamic acid).
abstract: 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.
authors.affiliation: UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, U.K.
authors.forename: Abeer H A
authors.initials: AH
authors.lastname: Mohamed-Ahmed
authors.forename: Karolina A
authors.initials: KA
authors.lastname: Les
authors.forename: Karin
authors.initials: K
authors.lastname: Seifert
authors.forename: Simon L
authors.initials: SL
authors.lastname: Croft
authors.forename: Stephen
authors.initials: S
authors.lastname: Brocchini
mesh_terms: D000666:Amphotericin B / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D018698:Glutamic Acid / Q000737:chemistry*; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects; D018320:Leishmania major / Q000187:drug effects / Q000472:pathogenicity; D007896:Leishmaniasis / Q000188:drug therapy; D012995:Solubility
chemical_list: D018698:Glutamic Acid; D000666:Amphotericin B