Development and characterization of PLGA nanoparticles containing 17-DMAG, an Hsp90 inhibitor
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/47662 |
Resumo: | Bahia State Research Support Foundation (PV-Universal 422867/2016-0 and SUS0019/2014) |
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Cruz, Kercia P.Patricio, Beatriz F. C.Pires, Vinícius C.Amorim, Marina F.Pinho, Alan G. S. F.Quadros, Helenita C.Dantas, Diana A. S.Chaves, Marcelo H. C.Formiga, Fabio RochaRocha, Helvécio V. A.Veras, Patrícia Sampaio Tavares2021-06-14T12:59:18Z2021-06-14T12:59:18Z2021CRUZ, Kercia P. et al. Development and characterization of PLGA nanoparticles containing 17-DMAG, an Hsp90 inhibitor. Frontiers in Chemistry, v. 9, p. 1-11, 13 May 2021.2296-2646https://www.arca.fiocruz.br/handle/icict/4766210.3389/fchem.2021.644827Bahia State Research Support Foundation (PV-Universal 422867/2016-0 and SUS0019/2014)FIOCRUZ (INOVA-46700287000)Gonçalo Moniz Institute (PV-PROEP 400898/2013-6)CNPq (305235/2019-2)Coordination for the Improvement of Higher Education Personnel-Brazil (CAPES)-Finance Code 001Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Laboratório de Micro e Nanotecnologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Laboratório de Micro e Nanotecnologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Departamento de Imunologia. Recife, PE, Brasil / Universidade de Pernambuco. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Laboratório de Micro e Nanotecnologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Interação Parasito-Hospedeiro e Epidemiologia. Salvador, BA, Brasil / Conselho Nacional de Desenvolvimento Científico e Tecnológico. Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Salvador, BA, Brasil.Leishmaniasis is a spectrum of neglected tropical diseases and its cutaneous form (CL) is characterized by papillary or ulcerated skin lesions that negatively impact patients’ quality of life. Current CL treatments suffer limitations, such as severe side effects and high cost, making the search for new therapeutic alternatives an imperative. In this context, heat shock protein 90 (Hsp90) could present a novel therapeutic target, as evidence suggests that Hsp90 inhibitors, such as 17-Dimethylaminoethylamino-17-Demethoxygeldanamycin (17-DMAG), may represent promising chemotherapeutic agents against CL. As innovative input for formulation development of 17-DMAG, nano-based drug delivery systems could provide controlled release, targeting properties, and reduced drug toxicity. In this work, a double emulsion method was used to develop poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing 17-DMAG. The nanoparticle was developed using two distinct protocols: Protocol 1 (P1) and Protocol 2 (P2), which differed concerning the organic solvent (acetone or dichloromethane, respectively) and procedure used to form doubleemulsions (Ultra-Turrax® homogenization or sonication, respectively). The nanoparticles produced by P2 were comparatively smaller (305.5 vs. 489.0 nm) and more homogeneous polydispersion index (PdI) (0.129 vs. 0.33) than the ones made by P1. Afterward, the P2 was optimized and the best composition consisted of 2 mg of 17-DMAG, 100 mg of PLGA, 5% of polyethylene glycol (PEG 8000), 1.5 mL of the internal aqueous phase, 1% of polyvinyl alcohol (PVA), and 4 mL of the organic phase. Optimized P2 nanoparticles had a particle size of 297.2 nm (288.6–304.1) and encapsulation efficacy of 19.35% (15.42–42.18) by the supernatant method and 31.60% (19.9–48.79) by the filter/column method. Release kinetics performed at 37◦C indicated that ∼16% of the encapsulated 17-DMAG was released about to 72 h. In a separate set of experiments, a cell uptake assay employing confocal fluorescence microscopy revealed the internalization by macrophages of P2-optimized rhodamine B labeled nanoparticles at 30 min, 1, 2, 4, 6, 24, 48, and 72 h. Collectively, our results indicate the superior performance of P2 concerning the parameters used to assess nanoparticle development. Therefore, these findings warrant further research to evaluate optimized 17-DMAG-loaded nanoparticles (NP2-17-DMAG) for toxicity and antileishmanial effects in vitro and in vivo.engFrontiers MediaLeishmanioseHsp9017-DMAGEmulsão duplaPLGANanopartículasSistemas de liberação de medicamentosMacrófagosTamanho da partículaLeishmaniasisHsp9017-DMAGDouble emulsionPLGANanoparticlesDevelopment and characterization of PLGA nanoparticles containing 17-DMAG, an Hsp90 inhibitorinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83097https://www.arca.fiocruz.br/bitstream/icict/47662/1/license.txt36b51ef91c52b5338d9d29ba0cc807bcMD51ORIGINALCruz, Kercia P Development....pdfCruz, Kercia P 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| dc.title.en.fl_str_mv |
Development and characterization of PLGA nanoparticles containing 17-DMAG, an Hsp90 inhibitor |
| title |
Development and characterization of PLGA nanoparticles containing 17-DMAG, an Hsp90 inhibitor |
| spellingShingle |
Development and characterization of PLGA nanoparticles containing 17-DMAG, an Hsp90 inhibitor Cruz, Kercia P. Leishmaniose Hsp90 17-DMAG Emulsão dupla PLGA Nanopartículas Sistemas de liberação de medicamentos Macrófagos Tamanho da partícula Leishmaniasis Hsp90 17-DMAG Double emulsion PLGA Nanoparticles |
| title_short |
Development and characterization of PLGA nanoparticles containing 17-DMAG, an Hsp90 inhibitor |
| title_full |
Development and characterization of PLGA nanoparticles containing 17-DMAG, an Hsp90 inhibitor |
| title_fullStr |
Development and characterization of PLGA nanoparticles containing 17-DMAG, an Hsp90 inhibitor |
| title_full_unstemmed |
Development and characterization of PLGA nanoparticles containing 17-DMAG, an Hsp90 inhibitor |
| title_sort |
Development and characterization of PLGA nanoparticles containing 17-DMAG, an Hsp90 inhibitor |
| author |
Cruz, Kercia P. |
| author_facet |
Cruz, Kercia P. Patricio, Beatriz F. C. Pires, Vinícius C. Amorim, Marina F. Pinho, Alan G. S. F. Quadros, Helenita C. Dantas, Diana A. S. Chaves, Marcelo H. C. Formiga, Fabio Rocha Rocha, Helvécio V. A. Veras, Patrícia Sampaio Tavares |
| author_role |
author |
| author2 |
Patricio, Beatriz F. C. Pires, Vinícius C. Amorim, Marina F. Pinho, Alan G. S. F. Quadros, Helenita C. Dantas, Diana A. S. Chaves, Marcelo H. C. Formiga, Fabio Rocha Rocha, Helvécio V. A. Veras, Patrícia Sampaio Tavares |
| author2_role |
author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Cruz, Kercia P. Patricio, Beatriz F. C. Pires, Vinícius C. Amorim, Marina F. Pinho, Alan G. S. F. Quadros, Helenita C. Dantas, Diana A. S. Chaves, Marcelo H. C. Formiga, Fabio Rocha Rocha, Helvécio V. A. Veras, Patrícia Sampaio Tavares |
| dc.subject.other.pt_BR.fl_str_mv |
Leishmaniose Hsp90 17-DMAG Emulsão dupla PLGA Nanopartículas Sistemas de liberação de medicamentos Macrófagos Tamanho da partícula |
| topic |
Leishmaniose Hsp90 17-DMAG Emulsão dupla PLGA Nanopartículas Sistemas de liberação de medicamentos Macrófagos Tamanho da partícula Leishmaniasis Hsp90 17-DMAG Double emulsion PLGA Nanoparticles |
| dc.subject.en.en.fl_str_mv |
Leishmaniasis Hsp90 17-DMAG Double emulsion PLGA Nanoparticles |
| description |
Bahia State Research Support Foundation (PV-Universal 422867/2016-0 and SUS0019/2014) |
| publishDate |
2021 |
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2021-06-14T12:59:18Z |
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2021-06-14T12:59:18Z |
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2021 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.citation.fl_str_mv |
CRUZ, Kercia P. et al. Development and characterization of PLGA nanoparticles containing 17-DMAG, an Hsp90 inhibitor. Frontiers in Chemistry, v. 9, p. 1-11, 13 May 2021. |
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https://www.arca.fiocruz.br/handle/icict/47662 |
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2296-2646 |
| dc.identifier.doi.pt_BR.fl_str_mv |
10.3389/fchem.2021.644827 |
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CRUZ, Kercia P. et al. Development and characterization of PLGA nanoparticles containing 17-DMAG, an Hsp90 inhibitor. Frontiers in Chemistry, v. 9, p. 1-11, 13 May 2021. 2296-2646 10.3389/fchem.2021.644827 |
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Frontiers Media |
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Frontiers Media |
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