Repurposing Butenafine as An Oral Nanomedicine for Visceral Leishmaniasis
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...
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| Format: | Article |
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MDPI AG
2019-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/7/353 |
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| author | Adriana Bezerra-Souza Raquel Fernandez-Garcia Gabriela F. Rodrigues Francisco Bolas-Fernandez Marcia Dalastra Laurenti Luiz Felipe Passero Aikaterini Lalatsa Dolores R. Serrano |
| author_facet | Adriana Bezerra-Souza Raquel Fernandez-Garcia Gabriela F. Rodrigues Francisco Bolas-Fernandez Marcia Dalastra Laurenti Luiz Felipe Passero Aikaterini Lalatsa Dolores R. Serrano |
| author_sort | Adriana Bezerra-Souza |
| collection | DOAJ |
| description | 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 <i>Leishmania infantum</i>. 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 <i>w</i>/<i>w</i>), which were then sprayed-dried with Aerosil 200 with a final 1:2 (Aerosil:liquid B-SNEDDS <i>w</i>/<i>w</i>) ratio. Spray-dried particles exhibited near-maximal drug loading, while maintaining excellent powder flow properties (angle of repose <10°) and sustained release in acidic gastrointestinal media. Solid-B-SNEDDS demonstrated greater selectivity index against promastigotes and <i>L. infantum</i>-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. |
| first_indexed | 2024-04-11T14:11:52Z |
| format | Article |
| id | doaj.art-d252f3f1162b45fda419612125730aaf |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T14:11:52Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-d252f3f1162b45fda419612125730aaf2022-12-22T04:19:42ZengMDPI AGPharmaceutics1999-49232019-07-0111735310.3390/pharmaceutics11070353pharmaceutics11070353Repurposing Butenafine as An Oral Nanomedicine for Visceral LeishmaniasisAdriana Bezerra-Souza0Raquel Fernandez-Garcia1Gabriela F. Rodrigues2Francisco Bolas-Fernandez3Marcia Dalastra Laurenti4Luiz Felipe Passero5Aikaterini Lalatsa6Dolores R. Serrano7Laboratory of Pathology of Infectious Diseases (LIM-50), Medical School, University of São Paulo, Avenida Dr. Arnaldo 455, 01246903 Cerqueira César, SP, BrazilDepartament of Pharmaceutics and Food Technology and Instituto Universitario de Farmacia Industrial (IUFI), School of Pharmacy, University Complutense, Avenida Complutense, 28040 Madrid, SpainLaboratory of Pathology of Infectious Diseases (LIM-50), Medical School, University of São Paulo, Avenida Dr. Arnaldo 455, 01246903 Cerqueira César, SP, BrazilDepartament of Microbiology and Parasitology, School of Pharmacy, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, SpainLaboratory of Pathology of Infectious Diseases (LIM-50), Medical School, University of São Paulo, Avenida Dr. Arnaldo 455, 01246903 Cerqueira César, SP, BrazilLaboratory of Pathology of Infectious Diseases (LIM-50), Medical School, University of São Paulo, Avenida Dr. Arnaldo 455, 01246903 Cerqueira César, SP, BrazilInstitute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, White Swan Road, Portsmouth PO1 2 DT, UKDepartament of Pharmaceutics and Food Technology and Instituto Universitario de Farmacia Industrial (IUFI), School of Pharmacy, University Complutense, Avenida Complutense, 28040 Madrid, SpainLeishmaniasis 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 <i>Leishmania infantum</i>. 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 <i>w</i>/<i>w</i>), which were then sprayed-dried with Aerosil 200 with a final 1:2 (Aerosil:liquid B-SNEDDS <i>w</i>/<i>w</i>) ratio. Spray-dried particles exhibited near-maximal drug loading, while maintaining excellent powder flow properties (angle of repose <10°) and sustained release in acidic gastrointestinal media. Solid-B-SNEDDS demonstrated greater selectivity index against promastigotes and <i>L. infantum</i>-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.https://www.mdpi.com/1999-4923/11/7/353butenafineSNEDDSsolid SNEDDSspray dryingleishmaniasisdesign of experiments |
| spellingShingle | Adriana Bezerra-Souza Raquel Fernandez-Garcia Gabriela F. Rodrigues Francisco Bolas-Fernandez Marcia Dalastra Laurenti Luiz Felipe Passero Aikaterini Lalatsa Dolores R. Serrano Repurposing Butenafine as An Oral Nanomedicine for Visceral Leishmaniasis Pharmaceutics butenafine SNEDDS solid SNEDDS spray drying leishmaniasis design of experiments |
| title | Repurposing Butenafine as An Oral Nanomedicine for Visceral Leishmaniasis |
| title_full | Repurposing Butenafine as An Oral Nanomedicine for Visceral Leishmaniasis |
| title_fullStr | Repurposing Butenafine as An Oral Nanomedicine for Visceral Leishmaniasis |
| title_full_unstemmed | Repurposing Butenafine as An Oral Nanomedicine for Visceral Leishmaniasis |
| title_short | Repurposing Butenafine as An Oral Nanomedicine for Visceral Leishmaniasis |
| title_sort | repurposing butenafine as an oral nanomedicine for visceral leishmaniasis |
| topic | butenafine SNEDDS solid SNEDDS spray drying leishmaniasis design of experiments |
| url | https://www.mdpi.com/1999-4923/11/7/353 |
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