Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.jsps.2019.11.018 http://hdl.handle.net/11449/199875 |
Resumo: | Background: The 6-mercaptopurine (6-MP) is an effective immunosuppressant and anti-cancer drug. However, the usage of 6-MP is limited due to its well-known side effects, such as myelotoxicity and hepato-renal toxicity. To curtail the potential toxic effects, we have used chitosan as a natural biodegradable and biocompatible polysaccharide to synthesize 6-Mercaptopurine-Chitosan Nanoparticles (6-MP-CNPs). Methods: The 6-MP-CNPssize, morphology, physicochemical interactions, and thermal stability were characterized using Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and Differential Scanning Calorimetry (DSC), respectively. The loading efficiency of the 6-MP in CNPs was estimated using LCMS/MS. Then, the 6-MP-CNPs were subjected to in vivo acute and sub-acute oral toxicity evaluations. Results: The DLS and SEM analysis respectively indicated size (70.0 nm to 400.0 nm), polydispersity index (0.462), and zeta potential (54.9 mV) with improved morphology of 6-MP-CNPs. The FTIR and DSC results showed the efficient interactive and stable nature of the 6-MP-CNPs, which sustained the drug-delivery process. The loading efficiency of 6-MP-CNPs was found to be 25.23%. The chitosan improved the lethal dose (LD50 cut off) of 6-MP-CNPs (1000 mg/kg b.w) against 6-MP (500 mg/kg b.w) and also significantly (p ≤ 0.05) reduces the toxic adverse effect (28-day repeated oral dose) on hemato-biochemical and hepato-renal histological profiles. Conclusion: The findings suggest that chitosan, as a prime drug-delivery carrier, significantly alleviates the acute and sub-acute toxic effects of 6-MP. |
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Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats6-MercaptopurineAnti-cancerChitosanNanoparticleToxicityBackground: The 6-mercaptopurine (6-MP) is an effective immunosuppressant and anti-cancer drug. However, the usage of 6-MP is limited due to its well-known side effects, such as myelotoxicity and hepato-renal toxicity. To curtail the potential toxic effects, we have used chitosan as a natural biodegradable and biocompatible polysaccharide to synthesize 6-Mercaptopurine-Chitosan Nanoparticles (6-MP-CNPs). Methods: The 6-MP-CNPssize, morphology, physicochemical interactions, and thermal stability were characterized using Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and Differential Scanning Calorimetry (DSC), respectively. The loading efficiency of the 6-MP in CNPs was estimated using LCMS/MS. Then, the 6-MP-CNPs were subjected to in vivo acute and sub-acute oral toxicity evaluations. Results: The DLS and SEM analysis respectively indicated size (70.0 nm to 400.0 nm), polydispersity index (0.462), and zeta potential (54.9 mV) with improved morphology of 6-MP-CNPs. The FTIR and DSC results showed the efficient interactive and stable nature of the 6-MP-CNPs, which sustained the drug-delivery process. The loading efficiency of 6-MP-CNPs was found to be 25.23%. The chitosan improved the lethal dose (LD50 cut off) of 6-MP-CNPs (1000 mg/kg b.w) against 6-MP (500 mg/kg b.w) and also significantly (p ≤ 0.05) reduces the toxic adverse effect (28-day repeated oral dose) on hemato-biochemical and hepato-renal histological profiles. Conclusion: The findings suggest that chitosan, as a prime drug-delivery carrier, significantly alleviates the acute and sub-acute toxic effects of 6-MP.H2020 LEIT NanotechnologiesDepartment of Orthopaedics and Rehabilitation College of Medicine The Pennsylvania State UniversityDepartment of Veterinary Pharmacology and Toxicology Veterinary College, HebbalDepartment of Molecular Pharmacology and Physiology Morsani College of Medicine University of South FloridaDepartment of Gynecology and Obstetrics Botucatu Medical School (FMB) São Paulo State University (UNESP)Innovative Nano and Micro Technologies Private Limited, Mysore RoadDepartment of Gynecology and Obstetrics Botucatu Medical School (FMB) São Paulo State University (UNESP)The Pennsylvania State UniversityVeterinary CollegeUniversity of South FloridaUniversidade Estadual Paulista (Unesp)Innovative Nano and Micro Technologies Private LimitedGovindappa, Prem KumarJoladarashi, DarukeshwaraHallur, Raghavendra Lakshmana Shetty [UNESP]Sanganal, Jagadeesh S.Phani, Ayyalasomayajula Ratna2020-12-12T01:51:41Z2020-12-12T01:51:41Z2020-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article147-154http://dx.doi.org/10.1016/j.jsps.2019.11.018Saudi Pharmaceutical Journal, v. 28, n. 1, p. 147-154, 2020.1319-0164http://hdl.handle.net/11449/19987510.1016/j.jsps.2019.11.0182-s2.0-85077146581Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengSaudi Pharmaceutical Journalinfo:eu-repo/semantics/openAccess2021-10-22T12:11:14Zoai:repositorio.unesp.br:11449/199875Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-22T12:11:14Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats |
title |
Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats |
spellingShingle |
Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats Govindappa, Prem Kumar 6-Mercaptopurine Anti-cancer Chitosan Nanoparticle Toxicity |
title_short |
Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats |
title_full |
Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats |
title_fullStr |
Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats |
title_full_unstemmed |
Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats |
title_sort |
Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats |
author |
Govindappa, Prem Kumar |
author_facet |
Govindappa, Prem Kumar Joladarashi, Darukeshwara Hallur, Raghavendra Lakshmana Shetty [UNESP] Sanganal, Jagadeesh S. Phani, Ayyalasomayajula Ratna |
author_role |
author |
author2 |
Joladarashi, Darukeshwara Hallur, Raghavendra Lakshmana Shetty [UNESP] Sanganal, Jagadeesh S. Phani, Ayyalasomayajula Ratna |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
The Pennsylvania State University Veterinary College University of South Florida Universidade Estadual Paulista (Unesp) Innovative Nano and Micro Technologies Private Limited |
dc.contributor.author.fl_str_mv |
Govindappa, Prem Kumar Joladarashi, Darukeshwara Hallur, Raghavendra Lakshmana Shetty [UNESP] Sanganal, Jagadeesh S. Phani, Ayyalasomayajula Ratna |
dc.subject.por.fl_str_mv |
6-Mercaptopurine Anti-cancer Chitosan Nanoparticle Toxicity |
topic |
6-Mercaptopurine Anti-cancer Chitosan Nanoparticle Toxicity |
description |
Background: The 6-mercaptopurine (6-MP) is an effective immunosuppressant and anti-cancer drug. However, the usage of 6-MP is limited due to its well-known side effects, such as myelotoxicity and hepato-renal toxicity. To curtail the potential toxic effects, we have used chitosan as a natural biodegradable and biocompatible polysaccharide to synthesize 6-Mercaptopurine-Chitosan Nanoparticles (6-MP-CNPs). Methods: The 6-MP-CNPssize, morphology, physicochemical interactions, and thermal stability were characterized using Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and Differential Scanning Calorimetry (DSC), respectively. The loading efficiency of the 6-MP in CNPs was estimated using LCMS/MS. Then, the 6-MP-CNPs were subjected to in vivo acute and sub-acute oral toxicity evaluations. Results: The DLS and SEM analysis respectively indicated size (70.0 nm to 400.0 nm), polydispersity index (0.462), and zeta potential (54.9 mV) with improved morphology of 6-MP-CNPs. The FTIR and DSC results showed the efficient interactive and stable nature of the 6-MP-CNPs, which sustained the drug-delivery process. The loading efficiency of 6-MP-CNPs was found to be 25.23%. The chitosan improved the lethal dose (LD50 cut off) of 6-MP-CNPs (1000 mg/kg b.w) against 6-MP (500 mg/kg b.w) and also significantly (p ≤ 0.05) reduces the toxic adverse effect (28-day repeated oral dose) on hemato-biochemical and hepato-renal histological profiles. Conclusion: The findings suggest that chitosan, as a prime drug-delivery carrier, significantly alleviates the acute and sub-acute toxic effects of 6-MP. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-12T01:51:41Z 2020-12-12T01:51:41Z 2020-01-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.jsps.2019.11.018 Saudi Pharmaceutical Journal, v. 28, n. 1, p. 147-154, 2020. 1319-0164 http://hdl.handle.net/11449/199875 10.1016/j.jsps.2019.11.018 2-s2.0-85077146581 |
url |
http://dx.doi.org/10.1016/j.jsps.2019.11.018 http://hdl.handle.net/11449/199875 |
identifier_str_mv |
Saudi Pharmaceutical Journal, v. 28, n. 1, p. 147-154, 2020. 1319-0164 10.1016/j.jsps.2019.11.018 2-s2.0-85077146581 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Saudi Pharmaceutical Journal |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
147-154 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1799965169025024000 |