Identification of transport systems involved in eflornithine delivery across the blood-brain barrier

Human African Trypanosomiasis (HAT) is a neglected parasitic disease that continues to persist in sub-Saharan Africa. It fatal if untreated. The first stage of the associated with presence parasite periphery and second parasites CNS. treatment CNS HAT requires drugs cross blood-brain barrier (BBB). Eflornithine an amino acid analogue used treat gambiense both alone combination nifurtimox. Recent studies have identified accumulation eflornithine into (trypanosomes) involves transporter ( Trypanosoma brucei AAT6). In this study we tested hypothesis uses cationic transport system BBB. We particularly focused on y + B 0,+ . To do utilized specialist databases compare physicochemical characteristics relevant molecules vitro model BBB explore mechanisms delivery Our results confirmed related endogenous acid, ornithine. At pH 7.4, predominately (92.39%) zwitterionic (dipolar) ornithine (99.08%) (tripolar) acid. addition, gross charge distribution at 7.4 much smaller (+0.073) than (+0.99). Further indicated saturable mechanism(s) hCMEC/D3 cell membranes was inhibited by other acids including also sodium-independent sensitive inhibitor, but not inhibitor. pentamidine, suggestive organic cation transporters (OCT) which are expressed line. expression protein, CAT1, ATB , cells. conclude transporter, OCT This research highlights potential deliver drugs, eflornithine, across brain diseases.