Transferrin as a Drug Carrier in African Trypanosomes

Abstract

We have coupled ¹⁴C-Samorin to bovine transferrin (Tf) using 2- azidophenyl glyoxal (APG), Samorin-APG-Tf was incubated with either the Trypanosoma congolense Samorin-sensitive (IL 1180) or Samorin-resistant (IL 3338.2) The APG-Tf conjugate without bound drug was used as the control. Trypanosoma congolense IL 1180 grew poorly even at Samorin/Tf concentrations as low as 0.12 ng drug/0.14 μg Tf per ml. Free Samorin kills Trypanosoma IL 1180 at a dose of 1ng/ml. The efficacy of the drug/Tf complex was as least as effective as free drug alone even in the presence of high amounts of serum Tf present in medium. The situation with the Samorin resistant T. congolense clone IL 3338.2 was quite different. This clone is sensitive to the effects of Samorin-APG-Tf at drug concentrations of 10ng/ml or higher. Surprisingly, the control APG-Tf conjugate was able to inhibit the growth of both Trypanosoma lL 1180 and IL 3338.2, albeit at similarly high Tf concentrations: 24.2-48.5 μg APG-Tf/ml. The data demonstrate the potential use of Tf as a novel drug delivery system in T. congolense. This finding has far reaching implications in the treatment of human sleeping sickness as Tf is one of the few serum proteins that is able to cross the blood-brain barrier.