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ZIF-8 as a promising drug delivery system for benznidazole: development, characterization, in vitro dialysis release and cytotoxicity
Chagas disease (CD), caused by the flagellate protozoan Trypanosoma cruzi , is one of the major public health problems in developing countries. Benznidazole (BNZ) is the only drug available for CD treatment in most countries, however, it presents high toxicity and low bioavailability. To address the...
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Published in: | Scientific reports 2020-10, Vol.10 (1), p.16815, Article 16815 |
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creator | de Moura Ferraz, Leslie Raphael Tabosa, Alinne Élida Gonçalves Alves da Silva Nascimento, Débora Dolores Souza Ferreira, Aline Silva de Albuquerque Wanderley Sales, Victor Silva, José Yago Rodrigues Júnior, Severino Alves Rolim, Larissa Araújo de Souza Pereira, Jorge José Rolim-Neto, Pedro José |
description | Chagas disease (CD), caused by the flagellate protozoan
Trypanosoma cruzi
, is one of the major public health problems in developing countries. Benznidazole (BNZ) is the only drug available for CD treatment in most countries, however, it presents high toxicity and low bioavailability. To address these problems this study used Zeolitic Imidazolate Framework-8 (ZIF-8), which has garnered considerable attention due to its potential applications, enabling the controlled delivery of drugs. The present work developed and characterized a BNZ@ZIF-8 system, and the modulation of BNZ release from the ZIF-8 framework was evaluated through the in vitro dialysis release method under sink conditions at different pH values. Moreover, the in vitro evaluation of cell viability and cytotoxicity by MTT assay were also performed. The dissolution studies corroborated that a pH sensitive Drug Delivery System capable of vectorizing the release of BNZ was developed, may leading to the improvement in the bioavailability of BNZ. The MTT assay showed that no statistically significant toxic effects occurred in the developed system, nor significant effects on cell viability. |
doi_str_mv | 10.1038/s41598-020-73848-w |
format | article |
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Trypanosoma cruzi
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Trypanosoma cruzi
, is one of the major public health problems in developing countries. Benznidazole (BNZ) is the only drug available for CD treatment in most countries, however, it presents high toxicity and low bioavailability. To address these problems this study used Zeolitic Imidazolate Framework-8 (ZIF-8), which has garnered considerable attention due to its potential applications, enabling the controlled delivery of drugs. The present work developed and characterized a BNZ@ZIF-8 system, and the modulation of BNZ release from the ZIF-8 framework was evaluated through the in vitro dialysis release method under sink conditions at different pH values. Moreover, the in vitro evaluation of cell viability and cytotoxicity by MTT assay were also performed. The dissolution studies corroborated that a pH sensitive Drug Delivery System capable of vectorizing the release of BNZ was developed, may leading to the improvement in the bioavailability of BNZ. The MTT assay showed that no statistically significant toxic effects occurred in the developed system, nor significant effects on cell viability.</description><subject>631/154/152</subject><subject>639/301/357/404</subject><subject>639/925/930/1032</subject><subject>639/925/930/12</subject><subject>692/308/153</subject><subject>692/699/255</subject><subject>692/699/255/1715</subject><subject>Dialysis</subject><subject>Drug Carriers</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>Imidazoles</subject><subject>multidisciplinary</subject><subject>Nitroimidazoles - administration & dosage</subject><subject>Nitroimidazoles - adverse effects</subject><subject>Nitroimidazoles - pharmacokinetics</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Spectrometry, X-Ray Emission</subject><subject>Spectroscopy, Fourier Transform Infrared</subject><subject>Trypanocidal Agents - administration & dosage</subject><subject>Trypanocidal Agents - adverse effects</subject><subject>Trypanocidal Agents - pharmacokinetics</subject><subject>Zeolites</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kU1uFDEQhS0EIlGSC7BAPkCa-HfsZoGEIkIiRWITNmysarc9cdRtj2zPhJ4998YwEIUNtXBZqvdeWf4QekPJO0q4viiCyl53hJFOcS109_gCHTMiZMc4Yy-f3Y_QWSkPpJVkvaD9a3TEOeGcM32Mfny7ueo0hoIBb3KaQwlxjce8bYebws7lBZelVDdjnzIeXNzHMMI-Te59U-zclDazi_Uc23vIYKvLYQ81pHiOQ8S7UHPCY4BpKaHg7CYHxWGII7ZLTTV9DzbU5RS98jAVd_ann6CvV5_uLq-72y-fby4_3nZWiFXtuODgidROSjqMmvWK-xUbtLQDVcL2oMBTb-VKKTnKldfM9qz3HiQZwSrPT9CHQ-5mO8xutO3hGSazyWGGvJgEwfw7ieHerNPOKCkkVaQFsEOAzamU7PyTlxLzi4s5cDGNi_nNxTw209vnW58sfyk0AT8IShvFtcvmIW1zbD_xv9ifq1ueEA</recordid><startdate>20201008</startdate><enddate>20201008</enddate><creator>de Moura Ferraz, Leslie Raphael</creator><creator>Tabosa, Alinne Élida Gonçalves Alves</creator><creator>da Silva Nascimento, Débora Dolores Souza</creator><creator>Ferreira, Aline Silva</creator><creator>de Albuquerque Wanderley Sales, Victor</creator><creator>Silva, José Yago Rodrigues</creator><creator>Júnior, Severino Alves</creator><creator>Rolim, Larissa Araújo</creator><creator>de Souza Pereira, Jorge José</creator><creator>Rolim-Neto, Pedro José</creator><general>Nature Publishing Group UK</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20201008</creationdate><title>ZIF-8 as a promising drug delivery system for benznidazole: development, characterization, in vitro dialysis release and cytotoxicity</title><author>de Moura Ferraz, Leslie Raphael ; Tabosa, Alinne Élida Gonçalves Alves ; da Silva Nascimento, Débora Dolores Souza ; Ferreira, Aline Silva ; de Albuquerque Wanderley Sales, Victor ; Silva, José Yago Rodrigues ; Júnior, Severino Alves ; Rolim, Larissa Araújo ; de Souza Pereira, Jorge José ; Rolim-Neto, Pedro José</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-343af058e551bd82973f62b85cb174c9a7af1fc56775d56f82c929ffa50dac7f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>631/154/152</topic><topic>639/301/357/404</topic><topic>639/925/930/1032</topic><topic>639/925/930/12</topic><topic>692/308/153</topic><topic>692/699/255</topic><topic>692/699/255/1715</topic><topic>Dialysis</topic><topic>Drug Carriers</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Hydrogen-Ion Concentration</topic><topic>Imidazoles</topic><topic>multidisciplinary</topic><topic>Nitroimidazoles - administration & dosage</topic><topic>Nitroimidazoles - adverse effects</topic><topic>Nitroimidazoles - pharmacokinetics</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Spectrometry, X-Ray Emission</topic><topic>Spectroscopy, Fourier Transform Infrared</topic><topic>Trypanocidal Agents - administration & dosage</topic><topic>Trypanocidal Agents - adverse effects</topic><topic>Trypanocidal Agents - pharmacokinetics</topic><topic>Zeolites</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Moura Ferraz, Leslie Raphael</creatorcontrib><creatorcontrib>Tabosa, Alinne Élida Gonçalves Alves</creatorcontrib><creatorcontrib>da Silva Nascimento, Débora Dolores Souza</creatorcontrib><creatorcontrib>Ferreira, Aline Silva</creatorcontrib><creatorcontrib>de Albuquerque Wanderley Sales, Victor</creatorcontrib><creatorcontrib>Silva, José Yago Rodrigues</creatorcontrib><creatorcontrib>Júnior, Severino Alves</creatorcontrib><creatorcontrib>Rolim, Larissa Araújo</creatorcontrib><creatorcontrib>de Souza Pereira, Jorge José</creatorcontrib><creatorcontrib>Rolim-Neto, Pedro José</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Moura Ferraz, Leslie Raphael</au><au>Tabosa, Alinne Élida Gonçalves Alves</au><au>da Silva Nascimento, Débora Dolores Souza</au><au>Ferreira, Aline Silva</au><au>de Albuquerque Wanderley Sales, Victor</au><au>Silva, José Yago Rodrigues</au><au>Júnior, Severino Alves</au><au>Rolim, Larissa Araújo</au><au>de Souza Pereira, Jorge José</au><au>Rolim-Neto, Pedro José</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ZIF-8 as a promising drug delivery system for benznidazole: development, characterization, in vitro dialysis release and cytotoxicity</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-10-08</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>16815</spage><pages>16815-</pages><artnum>16815</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Chagas disease (CD), caused by the flagellate protozoan
Trypanosoma cruzi
, is one of the major public health problems in developing countries. Benznidazole (BNZ) is the only drug available for CD treatment in most countries, however, it presents high toxicity and low bioavailability. To address these problems this study used Zeolitic Imidazolate Framework-8 (ZIF-8), which has garnered considerable attention due to its potential applications, enabling the controlled delivery of drugs. The present work developed and characterized a BNZ@ZIF-8 system, and the modulation of BNZ release from the ZIF-8 framework was evaluated through the in vitro dialysis release method under sink conditions at different pH values. Moreover, the in vitro evaluation of cell viability and cytotoxicity by MTT assay were also performed. The dissolution studies corroborated that a pH sensitive Drug Delivery System capable of vectorizing the release of BNZ was developed, may leading to the improvement in the bioavailability of BNZ. The MTT assay showed that no statistically significant toxic effects occurred in the developed system, nor significant effects on cell viability.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33033328</pmid><doi>10.1038/s41598-020-73848-w</doi><oa>free_for_read</oa></addata></record> |
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subjects | 631/154/152 639/301/357/404 639/925/930/1032 639/925/930/12 692/308/153 692/699/255 692/699/255/1715 Dialysis Drug Carriers Humanities and Social Sciences Humans Hydrogen-Ion Concentration Imidazoles multidisciplinary Nitroimidazoles - administration & dosage Nitroimidazoles - adverse effects Nitroimidazoles - pharmacokinetics Science Science (multidisciplinary) Spectrometry, X-Ray Emission Spectroscopy, Fourier Transform Infrared Trypanocidal Agents - administration & dosage Trypanocidal Agents - adverse effects Trypanocidal Agents - pharmacokinetics Zeolites |
title | ZIF-8 as a promising drug delivery system for benznidazole: development, characterization, in vitro dialysis release and cytotoxicity |
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