Repositioning of Tamoxifen in Surface-Modified Nanocapsules as a Promising Oral Treatment for Visceral Leishmaniasis
| Autor: | Simone Aparecida Rezende, Débora Faria Silva, Gwenaelle Pound-Lana, Levi Eduardo Soares Reis, Alexandre Barbosa Reis, Douglas Daniel Dophine, José Mário Carneiro Vilela, Vinicius Roberto de Andrade, Vanessa Carla Furtado Mosqueira, Marina Guimarães Carvalho Machado, Wanderson Geraldo de Lima, Margareth Spangler Andrade |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
PEG-PLA Biodistribution Meglumine antimoniate 030106 microbiology efficacy repurposing Pharmaceutical Science Hamster Spleen Pharmacology Article Nanocapsules 03 medical and health sciences Pharmacy and materia medica In vivo physicochemical characterization medicine nanocapsule leishmaniasis drug release tamoxifen business.industry Leishmaniasis medicine.disease RS1-441 030104 developmental biology Visceral leishmaniasis medicine.anatomical_structure business medicine.drug |
| Zdroj: | Pharmaceutics Volume 13 Issue 7 Pharmaceutics, Vol 13, Iss 1061, p 1061 (2021) |
| ISSN: | 1999-4923 |
| DOI: | 10.3390/pharmaceutics13071061 |
| Popis: | 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-block-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. |
| Databáze: | OpenAIRE |
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