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(+).

The In Vitro Efficacy of Antimicrobial Agents Against the Pathogenic Free‐Living Amoeba Balamuthia mandrillaris

“…It would, therefore, be of interest to conduct similar studies to establish the protective or curative effects of diminazene aceturate compared to the appropriate control groups. Recent studies have also shown that colloidal nanoparticle formulations of diminazene exhibited greater activity against T. brucei brucei in vitro and had increased delivery to the brain in mice (Kroubi et al 2010(Kroubi et al , 2011.…”

“…Recent studies have also shown that colloidal nanoparticle formulations of diminazene exhibited greater activity against T. brucei brucei in vitro and had increased delivery to the brain in mice (Kroubi et al. , ).…”

Application of some nanoparticles in the field of veterinary medicine

“…The porous cationic nanoparticles used stepped forward the potential focused on of trypanosomes. Evaluation of medical parameters after nanoparticle treatment revealed a partial reduction of allergic conditions [93].…”

Nanotechnology applications in veterinary diagnostics and therapeutics

“…Several other reports show the usefulness of nanoparticles in disease diagnosis (Na et al, 2009;Jackson et al, 2011;Schlacter et al, 2011;Huang et al, 2012). Nanotechnology is currently employed in the treatment of African animal trypanosomosis (Kroubi et al, 2010). It enabled the development of a new drug delivery system against diaminazene (DMZ) a trypanocidal drug registered for veterinary use.…”