Solving the challenge of the blood–brain barrier to treat infections caused by Trypanosoma evansi: evaluation of nerolidol-loaded nanospheres in mice

• Published in: Parasitology Vol. 144; no. 11; pp. 1543 - 1550
• Main Authors: BALDISSERA, MATHEUS D., SOUZA, CARINE F., BOLIGON, ALINE A., GRANDO, THIRSSA H., DE SÁ, MARIÂNGELA F., DA SILVA, ALEKSANDRO S., STEFANI, LENITA M., BALDISSEROTTO, BERNARDO, MONTEIRO, SILVIA G.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.09.2017
• Subjects: Alzheimer's disease; Animal cognition; Animals; Blood-Brain Barrier; Brain - drug effects; Central nervous system; Drug delivery systems; High performance liquid chromatography; Horses; Liquid chromatography; Mice; Nanospheres; Nanotechnology; Nanotechnology - methods; Nerolidol; Nervous system; Neurological disorders; Parasites; Parasitic diseases; Parasitology; Particle size; Polymerase chain reaction; Sesquiterpenes - administration & dosage; Sesquiterpenes - chemistry; Sesquiterpenes - therapeutic use; Transmission electron microscopy; Trypanocidal Agents - administration & dosage; Trypanocidal Agents - chemistry; Trypanocidal Agents - therapeutic use; Trypanosoma - drug effects; Trypanosoma evansi; Trypanosoma vivax; Trypanosomiasis - drug therapy; Trypanosomiasis - parasitology; nanotechnology; natural products; central nervous system
• ISSN: 0031-1820; 1469-8161
• DOI: 10.1017/S003118201700110X

Despite significant advances in therapies against Trypanosoma evansi, its effective elimination from the central nervous system (CNS) remains a difficult task. The incapacity of trypanocidal drugs to cross the blood–brain barrier (BBB) after systemic administrations makes the brain the main refuge area for T. evansi. Nanotechnology is showing great potential to improve drug efficacy, such as nerolidol-loaded nanospheres (N-NS). Thus, the aim of this study was to investigate whether the treatment with N-NS was able to cross the BBB and to eliminate T. evansi from the CNS. High-performance liquid chromatography revealed that N-NS can cross the BBB of T. evansi-infected mice, while free nerolidol (F-N) neither the trypanocidal drug diminazene aceturate (D.A.) were not detected in the brain tissue. Polymerase chain reaction revealed that 100% of the animals treated with N-NS were negatives for T. evansi in the brain tissue, while all infected animals treated with F-N or D.A. were positives. Thus, we concluded that nanotechnology improves the therapeutic efficacy of nerolidol, and enables the transport of its active principle through the BBB. In summary, N-NS treatment can eliminate the parasite from the CNS, and possesses potential to treat infected animals.