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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Repurposing Butenafine as An Oral Nanomedicine for Visceral Leishmaniasis

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Bezerra-Souza, Adriana [1] ; Fernandez-Garcia, Raquel [2, 3] ; Rodrigues, Gabriela F. [1] ; Bolas-Fernandez, Francisco [4] ; Laurenti, Marcia Dalastra [1] ; Passero, Luiz Felipe [5, 1] ; Lalatsa, Aikaterini [6] ; Serrano, Dolores R. [2, 3]
Total Authors: 8
[1] Univ Sao Paulo, Med Sch, Lab Pathol Infect Dis LIM 50, Ave Dr Arnaldo 455, BR-01246903 Sao Paulo, SP - Brazil
[2] Univ Complutense, Dept Pharmaceut & Food Technol, Sch Pharm, Ave Complutense, E-28040 Madrid - Spain
[3] Univ Complutense, IUFI, Sch Pharm, Ave Complutense, E-28040 Madrid - Spain
[4] Univ Complutense Madrid, Dept Microbiol & Parasitol, Sch Pharm, Plaza Ramon y Cajal S-N, E-28040 Madrid - Spain
[5] Sao Paulo State Univ UNESP, Inst Biosci, Praca Infante Dom Henrique S-N, BR-11330900 Sao Vicente, SP - Brazil
[6] Univ Portsmouth, Sch Pharm & Biomed Sci, Inst Biomed & Biomol Sci, Portsmouth PO1 2DT, Hants - England
Total Affiliations: 6
Document type: Journal article
Source: PHARMACEUTICS; v. 11, n. 7 JUL 2019.
Web of Science Citations: 0

Leishmaniasis is a neglected tropical disease affecting more than 12 million people worldwide, which in its visceral clinical form (VL) is characterised by the accumulation of parasites in the liver and spleen, and can lead to death if not treated. Available treatments are not well tolerated due to severe adverse effects, need for parenteral administration and patient hospitalisation, and long duration of expensive treatments. These treatment realities justify the search for new effective drugs, repurposing existing licensed drugs towards safer and non-invasive cost-effective medicines for VL. In this work, we provide proof of concept studies of butenafine and butenafine self-nanoemulsifying drug delivery systems (B-SNEDDS) against Leishmania infantum. Liquid B-SNEDDS were optimised using design of experiments, and then were spray-dried onto porous colloidal silica carriers to produce solid-B-SNEDDS with enhanced flow properties and drug stability. Optimal liquid B-SNEDDS consisted of Butenafine:Capryol 90:Peceol:Labrasol (3:49.5:24.2:23.3 w/w), which were then sprayed-dried with Aerosil 200 with a final 1:2 (Aerosil:liquid B-SNEDDS w/w) ratio. Spray-dried particles exhibited near-maximal drug loading, while maintaining excellent powder flow properties (angle of repose <10 degrees) and sustained release in acidic gastrointestinal media. Solid-B-SNEDDS demonstrated greater selectivity index against promastigotes and L. infantum-infected amastigotes than butenafine alone. Developed oral solid nanomedicines enable the non-invasive and safe administration of butenafine as a cost-effective and readily scalable repurposed medicine for VL. (AU)

FAPESP's process: 17/09405-4 - Evaluation of the therapeutic effect of butenafine in the American Tegumentar Leishmaniasis
Grantee:Adriana Bezerra de Souza
Support type: Scholarships in Brazil - Master
FAPESP's process: 16/00468-0 - Use of drug repurposing and natural product bioprospection to characterize compounds with in vitro and in vivo leishmanicidal action
Grantee:Luiz Felipe Domingues Passero
Support type: Regular Research Grants