Abstract
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-Mw and L-Mw) 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-Mw and L-Mw 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.
Original language | American English |
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Pages (from-to) | 1972-1977 |
Number of pages | 6 |
Journal | Biomacromolecules |
Volume | 11 |
Issue number | 8 |
DOIs | |
State | Published - 9 Aug 2010 |