Polysaccharide pharmacokinetics: amphotericin B arabinogalactan conjugate-a drug delivery system or a new pharmaceutical entity?

Anna Elgart, Shimon Farber, Abraham J Domb, Itzhack Polacheck, Amnon Hoffman

Institute for Drug Research, School of Pharmacy, and Department of Clinical Microbiology and Infectious Diseases, The Hebrew University of Jerusalem-Hadassah Medical Center, P.O. Box 12065, Jerusalem 91120, Israel.

Biomacromolecules 2010 Aug 9

filter terms:

Conjugation of poorly soluble drugs to polysaccharides affects their solubility, pharmacokinetics (PK), and pharmacodynamics. The need for amphotericin B (AmB) analog with improved solubility and reduced toxicity is immense. Conjugation of AmB to arabinogalactan (AG) produced a highly soluble AmB-AG conjugate, with high and low molecular weight (H-M(w) and L-M(w)) fractions. Its similar antifungal activity to AmB poses the question whether AmB-AG is a prodrug of AmB or a novel pharmaceutical entity. We compared the PK of AmB-AG and AmB in rats. Upon AmB-AG administration, no free AmB was released. The half-lives and the volumes of distribution of AmB, H-M(w) and L-M(w) were 10.9, 8.8, and 1.5 h and 1630, 217, and 133 mL/kg, respectively. We conclude that PK of small molecules conjugated to polysaccharides is mainly dictated by the macromolecular moiety and shows molecular weight dependency. Our findings define AmB-AG as a novel pharmaceutical entity with high clinical potential.

Citation

Anna Elgart, Shimon Farber, Abraham J Domb, Itzhack Polacheck, Amnon Hoffman. Polysaccharide pharmacokinetics: amphotericin B arabinogalactan conjugate-a drug delivery system or a new pharmaceutical entity? Biomacromolecules. 2010 Aug 9;11(8):1972-7