title: Development of a nanoparticulate formulation of diminazene to treat African trypanosomiasis.
abstract: There is a real need to develop new therapeutic strategies for African trypanosomiasis infections. In our study, we developed a new drug delivery system of diminazene (DMZ), a trypanocidal drug registered for veterinary use. This drug candidate presents a limited efficacy, a poor affinity for brain tissue and instability. The development of colloidal formulations based on a porous cationic nanoparticle with an oily core ((70)DGNP(+)), has potentially two advantages: stabilization of the drug and potential targeting of the parasite. We analyzed two processes of drug loading: in process (DMZ was added during the preparation of (70)DGNP(+) at 80 °C) and post-loading (DMZ was mixed with a (70)DGNP(+) solution at room temperature). Poor stability of the drug was observed using the in process technique. When using the post-loading technique over 80% drug entrapment efficiency was obtained at a ratio of DMZ:phospholipids (wt:wt) < 5%. Moreover, DMZ loaded into (70)DGNP(+) was found to be protected against oxidation and was stable for at least six months at 4 °C. Finally, in vitro tests on T.b. brucei showed an increased efficacy of DMZ loaded in (70)DGNP(+).
authors.affiliation: EA 4483, IFR 114 IMPRT, Faculté de Médecine, Pôle recherche, Département de Physiologie, 1 place de Verdun, 59045 Lille Cedex, France.
authors.forename: Maya
authors.initials: M
authors.lastname: Kroubi
authors.forename: Sylvie
authors.initials: S
authors.lastname: Daulouede
authors.forename: Hamadi
authors.initials: H
authors.lastname: Karembe
authors.forename: Youssef
authors.initials: Y
authors.lastname: Jallouli
authors.forename: Mike
authors.initials: M
authors.lastname: Howsam
authors.forename: Djavad
authors.initials: D
authors.lastname: Mossalayi
authors.forename: Philippe
authors.initials: P
authors.lastname: Vincendeau
authors.forename: Didier
authors.initials: D
authors.lastname: Betbeder
mesh_terms: D000818:Animals; D004133:Diminazene / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D004355:Drug Stability; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000737:chemistry; D014344:Trypanocidal Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D014346:Trypanosoma brucei brucei / Q000187:drug effects; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000662:veterinary*
chemical_list: D010743:Phospholipids; D014344:Trypanocidal Agents; D004133:Diminazene