Antileishmanial activity, uptake, and biodistribution of an amphotericin B and poly(α-Glutamic Acid) complex.

Abeer HA Mohamed-Ahmed; Karin Seifert; Vanessa Yardley; Hollie Burrell-Saward; Stephen Brocchini; Simon L Croft ORCID logo; (2013) Antileishmanial activity, uptake, and biodistribution of an amphotericin B and poly(α-Glutamic Acid) complex. Antimicrobial agents and chemotherapy, 57 (10). pp. 4608-4614. ISSN 0066-4804 DOI: 10.1128/AAC.02343-12
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A noncovalent, water-soluble complex of amphotericin B (AMB) and poly(α-glutamic acid) (PGA), with AMB loadings ranging from 25 to 55% (wt/wt) using PGA with a molecular weight range of 50,000 to 70,000, was prepared as a potential new treatment for visceral leishmaniasis (VL). The AMB-PGA complex was shown to be as active as Fungizone (AMB deoxycholate) against intracellular Leishmania donovani amastigotes in differentiated THP-1 cells. The in vitro uptake of the AMB-PGA complex by differentiated THP-1 cells was similar to that of Fungizone and higher than that of AmBisome (liposomal AMB). The AMB-PGA complex also displayed a dose-response profile similar to that of AmBisome in vivo in BALB/c mice against L. donovani, with 50% effective doses (ED50s) of 0.24 ± 0.03 mg/kg of body weight for the AMB-PGA complex and 0.24 ± 0.06 mg/kg for AmBisome. A biodistribution study with mice indicated that the AMB-PGA complex cleared more rapidly from plasma than AmBisome, with a comparable low level of distribution to the kidneys.

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