Repositioning of Tamoxifen in Surface-Modified Nanocapsules as a Promising Oral Treatment for Visceral Leishmaniasis
Standards of care for human visceral leishmaniasis (VL) are based on drugs used parenterally, and oral treatment options are urgently needed. In the present study, a repurposing strategy was used associating tamoxifen (TMX) with polyethylene glycol-<i>block</i>-polylactide nanocapsules (...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/7/1061 |
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| author | Débora Faria Silva Levi Eduardo Soares Reis Marina Guimarães Carvalho Machado Douglas Daniel Dophine Vinicius Roberto de Andrade Wanderson Geraldo de Lima Margareth Spangler Andrade José Mário Carneiro Vilela Alexandre Barbosa Reis Gwenaelle Pound-Lana Simone Aparecida Rezende Vanessa Carla Furtado Mosqueira |
| author_facet | Débora Faria Silva Levi Eduardo Soares Reis Marina Guimarães Carvalho Machado Douglas Daniel Dophine Vinicius Roberto de Andrade Wanderson Geraldo de Lima Margareth Spangler Andrade José Mário Carneiro Vilela Alexandre Barbosa Reis Gwenaelle Pound-Lana Simone Aparecida Rezende Vanessa Carla Furtado Mosqueira |
| author_sort | Débora Faria Silva |
| collection | DOAJ |
| description | Standards of care for human visceral leishmaniasis (VL) are based on drugs used parenterally, and oral treatment options are urgently needed. In the present study, a repurposing strategy was used associating tamoxifen (TMX) with polyethylene glycol-<i>block</i>-polylactide nanocapsules (NC) and its anti-leishmanial efficacy was reported in vivo. Stable surface modified-NC (5 mg/mL of TMX) exhibited 200 nm in size, +42 mV of zeta potential, and 98% encapsulation efficiency. Atomic force microscopy evidenced core-shell-NC. Treatment with TMX-NC reduced parasite-DNA quantified in liver and spleen compared to free-TMX; and provided a similar reduction of parasite burden compared with meglumine antimoniate in mice and hamster models. Image-guided biodistribution showed accumulation of NC in liver and spleen after 30 min post-administration. TMX-NC reduced the number of liver granulomas and restored the aspect of capsules and trabeculae in the spleen of infected animals. TMX-NC was tested for the first time against VL models, indicating a promising formulation for oral treatment. |
| first_indexed | 2024-03-10T09:28:23Z |
| format | Article |
| id | doaj.art-8436429fa60d49b3a83568ba377feda3 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T09:28:23Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-8436429fa60d49b3a83568ba377feda32023-11-22T04:41:25ZengMDPI AGPharmaceutics1999-49232021-07-01137106110.3390/pharmaceutics13071061Repositioning of Tamoxifen in Surface-Modified Nanocapsules as a Promising Oral Treatment for Visceral LeishmaniasisDébora Faria Silva0Levi Eduardo Soares Reis1Marina Guimarães Carvalho Machado2Douglas Daniel Dophine3Vinicius Roberto de Andrade4Wanderson Geraldo de Lima5Margareth Spangler Andrade6José Mário Carneiro Vilela7Alexandre Barbosa Reis8Gwenaelle Pound-Lana9Simone Aparecida Rezende10Vanessa Carla Furtado Mosqueira11Laboratory of Clinical Research, Pharmacy School, Federal University of Ouro Preto, Ouro Preto 35400-000, BrazilLaboratory of Immunopathology, Post-Graduate Program in Biological Sciences, Federal University of Ouro Preto, Ouro Preto 35400-000, BrazilLaboratory of Pharmaceutics and Nanotechnology, Pharmacy School, Federal University of Ouro Preto, Ouro Preto 35400-000, BrazilLaboratory of Clinical Research, Pharmacy School, Federal University of Ouro Preto, Ouro Preto 35400-000, BrazilLaboratory of Clinical Research, Pharmacy School, Federal University of Ouro Preto, Ouro Preto 35400-000, BrazilLaboratory of Morphopathology, Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Ouro Preto 35400-000, BrazilCenter–SENAI/CETEC, Laboratory of Nanoscopy, Belo Horizonte 31035-536, BrazilCenter–SENAI/CETEC, Laboratory of Nanoscopy, Belo Horizonte 31035-536, BrazilLaboratory of Immunopathology, Post-Graduate Program in Biological Sciences, Federal University of Ouro Preto, Ouro Preto 35400-000, BrazilLaboratory of Pharmaceutics and Nanotechnology, Pharmacy School, Federal University of Ouro Preto, Ouro Preto 35400-000, BrazilLaboratory of Clinical Research, Pharmacy School, Federal University of Ouro Preto, Ouro Preto 35400-000, BrazilLaboratory of Pharmaceutics and Nanotechnology, Pharmacy School, Federal University of Ouro Preto, Ouro Preto 35400-000, BrazilStandards of care for human visceral leishmaniasis (VL) are based on drugs used parenterally, and oral treatment options are urgently needed. In the present study, a repurposing strategy was used associating tamoxifen (TMX) with polyethylene glycol-<i>block</i>-polylactide nanocapsules (NC) and its anti-leishmanial efficacy was reported in vivo. Stable surface modified-NC (5 mg/mL of TMX) exhibited 200 nm in size, +42 mV of zeta potential, and 98% encapsulation efficiency. Atomic force microscopy evidenced core-shell-NC. Treatment with TMX-NC reduced parasite-DNA quantified in liver and spleen compared to free-TMX; and provided a similar reduction of parasite burden compared with meglumine antimoniate in mice and hamster models. Image-guided biodistribution showed accumulation of NC in liver and spleen after 30 min post-administration. TMX-NC reduced the number of liver granulomas and restored the aspect of capsules and trabeculae in the spleen of infected animals. TMX-NC was tested for the first time against VL models, indicating a promising formulation for oral treatment.https://www.mdpi.com/1999-4923/13/7/1061tamoxifenrepurposingleishmaniasisefficacynanocapsulephysicochemical characterization |
| spellingShingle | Débora Faria Silva Levi Eduardo Soares Reis Marina Guimarães Carvalho Machado Douglas Daniel Dophine Vinicius Roberto de Andrade Wanderson Geraldo de Lima Margareth Spangler Andrade José Mário Carneiro Vilela Alexandre Barbosa Reis Gwenaelle Pound-Lana Simone Aparecida Rezende Vanessa Carla Furtado Mosqueira Repositioning of Tamoxifen in Surface-Modified Nanocapsules as a Promising Oral Treatment for Visceral Leishmaniasis Pharmaceutics tamoxifen repurposing leishmaniasis efficacy nanocapsule physicochemical characterization |
| title | Repositioning of Tamoxifen in Surface-Modified Nanocapsules as a Promising Oral Treatment for Visceral Leishmaniasis |
| title_full | Repositioning of Tamoxifen in Surface-Modified Nanocapsules as a Promising Oral Treatment for Visceral Leishmaniasis |
| title_fullStr | Repositioning of Tamoxifen in Surface-Modified Nanocapsules as a Promising Oral Treatment for Visceral Leishmaniasis |
| title_full_unstemmed | Repositioning of Tamoxifen in Surface-Modified Nanocapsules as a Promising Oral Treatment for Visceral Leishmaniasis |
| title_short | Repositioning of Tamoxifen in Surface-Modified Nanocapsules as a Promising Oral Treatment for Visceral Leishmaniasis |
| title_sort | repositioning of tamoxifen in surface modified nanocapsules as a promising oral treatment for visceral leishmaniasis |
| topic | tamoxifen repurposing leishmaniasis efficacy nanocapsule physicochemical characterization |
| url | https://www.mdpi.com/1999-4923/13/7/1061 |
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