Publicação
Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity
| Resumo: | Clinical effectiveness of imatinib mesylate in cancer treatment is compromised by its off-target cardiotoxicity. In the present study, we have developed physically stable imatinib mesylate-loaded poly(lactide-co-glycolide) nanoparticles (INPs) that could sustainably release the drug, and studied its efficacy by in vitro anticancer and in vivo cardiotoxicity assays. MTT (methylthiazolyldiphenyl-tetrazolium bromide) assay revealed that INPs are more cytotoxic to MCF-7 breast cancer cells compared to the equivalent concentration of free imatinib mesylate. Wistar rats orally administered with 50 mg/kg INPs for 28 days showed no significant cardiotoxicity or associated changes. Whereas, increased alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels, and reduced white blood cell, red blood cell, and hemoglobin content were observed in the animals administered with free drug. While the histological sections from hearts of animals that received INPs did not show any significant cardiotoxic symptoms, loss of normal architecture and increased cytoplasmic vacuolization were observed in the heart sections of animals administered with free imatinib mesylate. Based on these results, we conclude that nano-encapsulation of imatinib mesylate increases its efficacy against cancer cells, with almost no cardiotoxicity. |
|---|---|
| Autores principais: | Marslin, Gregory |
| Outros Autores: | Revina, Ann Mary; Khandelwal, Vinoth Kumar Megraj; Balakumar, Krishnamoorthy; Prakash, Jose; Franklin, Gregory; Sheeba, Caroline J. |
| Assunto: | Imatinib nanoparticles Cytotoxicity Cardiotoxicity Hematology |
| Ano: | 2015 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1866876838876282880 |
|---|---|
| author | Marslin, Gregory |
| author2 | Revina, Ann Mary Khandelwal, Vinoth Kumar Megraj Balakumar, Krishnamoorthy Prakash, Jose Franklin, Gregory Sheeba, Caroline J. |
| author2_role | author author author author author author |
| author_facet | Marslin, Gregory Revina, Ann Mary Khandelwal, Vinoth Kumar Megraj Balakumar, Krishnamoorthy Prakash, Jose Franklin, Gregory Sheeba, Caroline J. |
| author_role | author |
| contributor_name_str_mv | Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Marslin, Gregory\"},{\"Person.name\":\"Revina, Ann Mary\"},{\"Person.name\":\"Khandelwal, Vinoth Kumar Megraj\"},{\"Person.name\":\"Balakumar, Krishnamoorthy\"},{\"Person.name\":\"Prakash, Jose\"},{\"Person.name\":\"Franklin, Gregory\"},{\"Person.name\":\"Sheeba, Caroline J.\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Marslin, Gregory Revina, Ann Mary Khandelwal, Vinoth Kumar Megraj Balakumar, Krishnamoorthy Prakash, Jose Franklin, Gregory Sheeba, Caroline J. |
| datacite.date.Accepted.fl_str_mv | 2015-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2016-02-12T15:41:06Z |
| datacite.date.embargoed.fl_str_mv | 2016-02-12T15:41:06Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Imatinib nanoparticles Cytotoxicity Cardiotoxicity Hematology |
| datacite.titles.title.fl_str_mv | Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity |
| dc.contributor.none.fl_str_mv | Universidade do Minho |
| dc.creator.none.fl_str_mv | Marslin, Gregory Revina, Ann Mary Khandelwal, Vinoth Kumar Megraj Balakumar, Krishnamoorthy Prakash, Jose Franklin, Gregory Sheeba, Caroline J. |
| dc.date.Accepted.fl_str_mv | 2015-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2016-02-12T15:41:06Z |
| dc.date.embargoed.fl_str_mv | 2016-02-12T15:41:06Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/40255 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Dove Press |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Imatinib nanoparticles Cytotoxicity Cardiotoxicity Hematology |
| dc.title.fl_str_mv | Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Clinical effectiveness of imatinib mesylate in cancer treatment is compromised by its off-target cardiotoxicity. In the present study, we have developed physically stable imatinib mesylate-loaded poly(lactide-co-glycolide) nanoparticles (INPs) that could sustainably release the drug, and studied its efficacy by in vitro anticancer and in vivo cardiotoxicity assays. MTT (methylthiazolyldiphenyl-tetrazolium bromide) assay revealed that INPs are more cytotoxic to MCF-7 breast cancer cells compared to the equivalent concentration of free imatinib mesylate. Wistar rats orally administered with 50 mg/kg INPs for 28 days showed no significant cardiotoxicity or associated changes. Whereas, increased alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels, and reduced white blood cell, red blood cell, and hemoglobin content were observed in the animals administered with free drug. While the histological sections from hearts of animals that received INPs did not show any significant cardiotoxic symptoms, loss of normal architecture and increased cytoplasmic vacuolization were observed in the heart sections of animals administered with free imatinib mesylate. Based on these results, we conclude that nano-encapsulation of imatinib mesylate increases its efficacy against cancer cells, with almost no cardiotoxicity. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://prod-dspace.uminho.pt/bitstreams/5a4c5e30-12be-4e8f-ae20-b161fa42cf96/download |
| id | rum_8e2d72e77463ece1dfa0e25b8ea2dbf2 |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/40255 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/40255 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Marslin, Gregory Revina, Ann Mary Khandelwal, Vinoth Kumar Megraj Balakumar, Krishnamoorthy Prakash, Jose Franklin, Gregory Sheeba, Caroline J. |
| publishDate | 2015 |
| publisher.none.fl_str_mv | Dove Press |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engDove PressporClinical effectiveness of imatinib mesylate in cancer treatment is compromised by its off-target cardiotoxicity. In the present study, we have developed physically stable imatinib mesylate-loaded poly(lactide-co-glycolide) nanoparticles (INPs) that could sustainably release the drug, and studied its efficacy by in vitro anticancer and in vivo cardiotoxicity assays. MTT (methylthiazolyldiphenyl-tetrazolium bromide) assay revealed that INPs are more cytotoxic to MCF-7 breast cancer cells compared to the equivalent concentration of free imatinib mesylate. Wistar rats orally administered with 50 mg/kg INPs for 28 days showed no significant cardiotoxicity or associated changes. Whereas, increased alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels, and reduced white blood cell, red blood cell, and hemoglobin content were observed in the animals administered with free drug. While the histological sections from hearts of animals that received INPs did not show any significant cardiotoxic symptoms, loss of normal architecture and increased cytoplasmic vacuolization were observed in the heart sections of animals administered with free imatinib mesylate. Based on these results, we conclude that nano-encapsulation of imatinib mesylate increases its efficacy against cancer cells, with almost no cardiotoxicity.application/pdfporDelivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activityMarslin, GregoryRevina, Ann MaryKhandelwal, Vinoth Kumar MegrajBalakumar, KrishnamoorthyPrakash, JoseFranklin, GregorySheeba, Caroline J.HostingInstitutionOrganizationalUniversidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptISSNIsPartOf1178-2013DOIIsPartOf10.2147/IJN.S759622016-02-12T15:41:06Z20152016-02-04T12:21:14Z2015-01-01T00:00:00ZHandlehttps://hdl.handle.net/1822/40255http://purl.org/coar/access_right/c_abf2open accessImatinib nanoparticlesCytotoxicityCardiotoxicityHematology1849039 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://prod-dspace.uminho.pt/bitstreams/5a4c5e30-12be-4e8f-ae20-b161fa42cf96/download |
| spellingShingle | Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity Marslin, Gregory Imatinib nanoparticles Cytotoxicity Cardiotoxicity Hematology |
| status | SINGLETON |
| subject.fl_str_mv | Imatinib nanoparticles Cytotoxicity Cardiotoxicity Hematology |
| title | Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity |
| title_full | Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity |
| title_fullStr | Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity |
| title_full_unstemmed | Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity |
| title_short | Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity |
| title_sort | Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity |
| topic | Imatinib nanoparticles Cytotoxicity Cardiotoxicity Hematology |
| topic_facet | Imatinib nanoparticles Cytotoxicity Cardiotoxicity Hematology |
| url | https://hdl.handle.net/1822/40255 |
| visible | 1 |