Dispositivo de liberação intravítrea para tratamento de degeneração macular relacionada à idade
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFG |
Texto Completo: | http://repositorio.bc.ufg.br/tede/handle/tede/12794 |
Resumo: | Age-related macular degeneration, AMD, is a chronic eye disease which damages the macular area. It is the main cause of adult blindness worldwide. The pharmacological treatment of choice for the neovascular form of AMD consists of intravitreal injections of anti-VEGF agents that, occasionally, might be combined with corticosteroids. Intravitreal injections are the preferred route for drug delivery to the posterior segment of the eye but have limited therapeutic success due to the quick elimination of substances, requiring frequent injections that bring complications to the patient and low adherence to treatment. Intravitreal implants are capable to maintain therapeutic levels of drugs for a long period. Biodegradable nanofibers can modulate drug release in addition to allowing the incorporation of fragile bioactive substances. The present work aimed the development of biodegradable intravitreal implants containing dexamethasone coated with polymeric nanofibers containing bevacizumab as a therapeutic proposal for the treatment of AMD. Nanocoated implants were successfully developed. The characterization of the system, the study of degradation and efficiency of the coating process were evaluated by scanning electron microscopy. The drug release profile was determined by high performance liquid cromatography and the Bradford method. The antiangiogenic activity was determined by the chicken embryo chorioallantoic membrane model. The safety of the formulation was evaluated in rabbit eyes. So far, the system was successfully developed. The study degradation study confirmed the presence of nanofibers on the implant surface for up to 35 days. The degradation study demonstrated the presence of nanofibers on the surface of the implant for up to 35 days. The release profile showed that 68% of dexamethasone was released within 35 days and 90% of bevacizumab within 48 hours. The formulation presented activity in reducing vessels and was safe for the rabbits’ retina. No clinical or histopathological changes were observed, neither alteration in retinal thickness by optical coherence tomography during the 28 days. The developed implants, therefore, may be considered as a new alternative for the treatment of AMD. |
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Cunha Júnior, Armando da Silvahttp://lattes.cnpq.br/8278273904187275Fialho, Sílvia Ligóriohttp://lattes.cnpq.br/6277013725246341Cunha Júnior, Armando da SilvaLima, Eliana MartinsDias, Marina FrançaDourado, Lays Fernanda NunesFialho, Silvia Ligóriohttp://lattes.cnpq.br/5373415064260730Guerra, Maria Carolina Andrade2023-04-28T11:11:01Z2023-04-28T11:11:01Z2023-04-04GUERRA, M. C. A. Dispositivo de liberação intravítrea para tratamento de degeneração macular relacionada à idade. 2023. 122 f. Tese (Doutorado em Nanotecnologia Farmacêutica em Rede) - Universidade Federal de Goiás, Belo Horizonte, 2023.http://repositorio.bc.ufg.br/tede/handle/tede/12794Age-related macular degeneration, AMD, is a chronic eye disease which damages the macular area. It is the main cause of adult blindness worldwide. The pharmacological treatment of choice for the neovascular form of AMD consists of intravitreal injections of anti-VEGF agents that, occasionally, might be combined with corticosteroids. Intravitreal injections are the preferred route for drug delivery to the posterior segment of the eye but have limited therapeutic success due to the quick elimination of substances, requiring frequent injections that bring complications to the patient and low adherence to treatment. Intravitreal implants are capable to maintain therapeutic levels of drugs for a long period. Biodegradable nanofibers can modulate drug release in addition to allowing the incorporation of fragile bioactive substances. The present work aimed the development of biodegradable intravitreal implants containing dexamethasone coated with polymeric nanofibers containing bevacizumab as a therapeutic proposal for the treatment of AMD. Nanocoated implants were successfully developed. The characterization of the system, the study of degradation and efficiency of the coating process were evaluated by scanning electron microscopy. The drug release profile was determined by high performance liquid cromatography and the Bradford method. The antiangiogenic activity was determined by the chicken embryo chorioallantoic membrane model. The safety of the formulation was evaluated in rabbit eyes. So far, the system was successfully developed. The study degradation study confirmed the presence of nanofibers on the implant surface for up to 35 days. The degradation study demonstrated the presence of nanofibers on the surface of the implant for up to 35 days. The release profile showed that 68% of dexamethasone was released within 35 days and 90% of bevacizumab within 48 hours. The formulation presented activity in reducing vessels and was safe for the rabbits’ retina. No clinical or histopathological changes were observed, neither alteration in retinal thickness by optical coherence tomography during the 28 days. The developed implants, therefore, may be considered as a new alternative for the treatment of AMD.A degeneração macular relacionada à idade (DMRI) é uma doença ocular crônica que causa danos à área central da retina. Está entre as principais causas de cegueira irreversível em adultos. O tratamento farmacológico de escolha utiliza injeções intravítreas de agentes anti-VEGF que ocasionalmente podem ser combinadas com corticosteróides. Injeções intravítreas são a via preferencial para administração de medicamentos ao segmento posterior do olho, porém apresentam sucesso terapêutico limitado devido à rápida eliminação de substâncias, exigindo injeções frequentes que podem trazer complicações ao paciente e baixa adesão ao tratamento. Implantes intravítreos são capazes de manter níveis terapêuticos de fármacos por um longo período. Nanofibras biodegradáveis podem modular a liberação de fármacos e permitir a incorporação de substâncias bioativas frágeis. O objetivo desse trabalho foi desenvolver implantes intravítreos biodegradáveis contendo dexametasona revestidos por nanofibras poliméricas contendo bevacizumabe como uma proposta terapêutica para o tratamento da DMRI. Os implantes nanorevestidos foram desenvolvidos. A caracterização do sistema, o estudo de degradação e eficiência do processo de revestimento foram avaliados por microscopia eletrônica de varredura. O perfil de liberação dos fármacos foi determinado por cromatografia líquida de alta eficiência e pelo método de Bradford. A atividade antiangiogênica foi determinada pelo modelo em membrana corioalantóica de embrião de galinha. A segurança da formulação foi avaliada em olhos de coelhos. O sistema foi desenvolvido com sucesso. O estudo de degradação demonstrou a presença de nanofibras na superfície do implante por até 35 dias. O perfil de liberação demonstrou que 68% da dexametasona foi liberada em 35 dias e 90% do bevacizumabe em 48h. A formulação apresentou atividade na redução de vasos e foi segura para a retina. Não foram observadas alterações clínica ou histopatológica, nem alteração na espessura da retina por tomografia ótica de coerência durante os 28 dias em que foi testado. Os implantes desenvolvidos podem, portanto, serem considerados como uma nova alternativa para o tratamento da DMRI.Submitted by Leandro Machado (leandromachado@ufg.br) on 2023-04-26T16:15:35Z No. of bitstreams: 2 Tese - Maria Carolina Andrade Guerra - 2023.pdf: 14071654 bytes, checksum: 85e998182dcaa4798eda328d2f9bc307 (MD5) license_rdf: 805 bytes, checksum: 4460e5956bc1d1639be9ae6146a50347 (MD5)Rejected by Luciana Ferreira (lucgeral@gmail.com), reason: Perguntou para Cláudia se o local é Belo Horizonte? e a ficha catalográfica, como deve ficar? Caso esteja errada a ficha catalográfica não precisa pedir para aluna arrumar, a essa altura. Pergunte para Cláudia se o correto é Fialho, Sílvia Ligório ou Ligório Fialho, Sílvia on 2023-04-27T10:58:06Z (GMT)Submitted by Leandro Machado (leandromachado@ufg.br) on 2023-04-27T15:13:02Z No. of bitstreams: 2 Tese - Maria Carolina Andrade Guerra - 2023.pdf: 14071654 bytes, checksum: 85e998182dcaa4798eda328d2f9bc307 (MD5) license_rdf: 805 bytes, checksum: 4460e5956bc1d1639be9ae6146a50347 (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2023-04-28T11:11:01Z (GMT) No. of bitstreams: 2 Tese - Maria Carolina Andrade Guerra - 2023.pdf: 14071654 bytes, checksum: 85e998182dcaa4798eda328d2f9bc307 (MD5) license_rdf: 805 bytes, checksum: 4460e5956bc1d1639be9ae6146a50347 (MD5)Made available in DSpace on 2023-04-28T11:11:01Z (GMT). No. of bitstreams: 2 Tese - Maria Carolina Andrade Guerra - 2023.pdf: 14071654 bytes, checksum: 85e998182dcaa4798eda328d2f9bc307 (MD5) license_rdf: 805 bytes, checksum: 4460e5956bc1d1639be9ae6146a50347 (MD5) Previous issue date: 2023-04-04OutroporUniversidade Federal de GoiásPrograma de Pós-graduação em Nanotecnologia Farmacêutica em Rede (FF)UFGBrasilFaculdade de Farmácia - FF (RMG)Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessDegeneração macular relacionada à idadeBevacizumabeNanofibrasNanotecnologiaImplante biodegradávelAplicação intravítreaAge-related macular degenerationBevacizumabNanofibersNanotechnologyBiodegradable implantIntravitreal applicationOUTROSDispositivo de liberação intravítrea para tratamento de degeneração macular relacionada à idadeNanofiber-coated intravitreal device for age-related macular degeneration treatmentinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis77500500500500229525reponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805http://repositorio.bc.ufg.br/tede/bitstreams/ed6f438c-5c2b-40c1-9ea1-7b8f97b9ba3e/download4460e5956bc1d1639be9ae6146a50347MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.bc.ufg.br/tede/bitstreams/0941aaa3-460a-4caf-99cc-d383010d2e41/download8a4605be74aa9ea9d79846c1fba20a33MD54ORIGINALTese - Maria Carolina Andrade Guerra - 2023.pdfTese - Maria Carolina Andrade Guerra - 2023.pdfapplication/pdf14071654http://repositorio.bc.ufg.br/tede/bitstreams/4d4591cd-91d9-4a23-a8e5-c9a9be0bdb1b/download85e998182dcaa4798eda328d2f9bc307MD53tede/127942023-04-28 08:11:02.301http://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 Internationalopen.accessoai:repositorio.bc.ufg.br:tede/12794http://repositorio.bc.ufg.br/tedeRepositório InstitucionalPUBhttp://repositorio.bc.ufg.br/oai/requesttasesdissertacoes.bc@ufg.bropendoar:2023-04-28T11:11:02Repositório Institucional da UFG - Universidade Federal de Goiás (UFG)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 |
dc.title.pt_BR.fl_str_mv |
Dispositivo de liberação intravítrea para tratamento de degeneração macular relacionada à idade |
dc.title.alternative.eng.fl_str_mv |
Nanofiber-coated intravitreal device for age-related macular degeneration treatment |
title |
Dispositivo de liberação intravítrea para tratamento de degeneração macular relacionada à idade |
spellingShingle |
Dispositivo de liberação intravítrea para tratamento de degeneração macular relacionada à idade Guerra, Maria Carolina Andrade Degeneração macular relacionada à idade Bevacizumabe Nanofibras Nanotecnologia Implante biodegradável Aplicação intravítrea Age-related macular degeneration Bevacizumab Nanofibers Nanotechnology Biodegradable implant Intravitreal application OUTROS |
title_short |
Dispositivo de liberação intravítrea para tratamento de degeneração macular relacionada à idade |
title_full |
Dispositivo de liberação intravítrea para tratamento de degeneração macular relacionada à idade |
title_fullStr |
Dispositivo de liberação intravítrea para tratamento de degeneração macular relacionada à idade |
title_full_unstemmed |
Dispositivo de liberação intravítrea para tratamento de degeneração macular relacionada à idade |
title_sort |
Dispositivo de liberação intravítrea para tratamento de degeneração macular relacionada à idade |
author |
Guerra, Maria Carolina Andrade |
author_facet |
Guerra, Maria Carolina Andrade |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Cunha Júnior, Armando da Silva |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/8278273904187275 |
dc.contributor.advisor-co1.fl_str_mv |
Fialho, Sílvia Ligório |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/6277013725246341 |
dc.contributor.referee1.fl_str_mv |
Cunha Júnior, Armando da Silva |
dc.contributor.referee2.fl_str_mv |
Lima, Eliana Martins |
dc.contributor.referee3.fl_str_mv |
Dias, Marina França |
dc.contributor.referee4.fl_str_mv |
Dourado, Lays Fernanda Nunes |
dc.contributor.referee5.fl_str_mv |
Fialho, Silvia Ligório |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/5373415064260730 |
dc.contributor.author.fl_str_mv |
Guerra, Maria Carolina Andrade |
contributor_str_mv |
Cunha Júnior, Armando da Silva Fialho, Sílvia Ligório Cunha Júnior, Armando da Silva Lima, Eliana Martins Dias, Marina França Dourado, Lays Fernanda Nunes Fialho, Silvia Ligório |
dc.subject.por.fl_str_mv |
Degeneração macular relacionada à idade Bevacizumabe Nanofibras Nanotecnologia Implante biodegradável Aplicação intravítrea |
topic |
Degeneração macular relacionada à idade Bevacizumabe Nanofibras Nanotecnologia Implante biodegradável Aplicação intravítrea Age-related macular degeneration Bevacizumab Nanofibers Nanotechnology Biodegradable implant Intravitreal application OUTROS |
dc.subject.eng.fl_str_mv |
Age-related macular degeneration Bevacizumab Nanofibers Nanotechnology Biodegradable implant Intravitreal application |
dc.subject.cnpq.fl_str_mv |
OUTROS |
description |
Age-related macular degeneration, AMD, is a chronic eye disease which damages the macular area. It is the main cause of adult blindness worldwide. The pharmacological treatment of choice for the neovascular form of AMD consists of intravitreal injections of anti-VEGF agents that, occasionally, might be combined with corticosteroids. Intravitreal injections are the preferred route for drug delivery to the posterior segment of the eye but have limited therapeutic success due to the quick elimination of substances, requiring frequent injections that bring complications to the patient and low adherence to treatment. Intravitreal implants are capable to maintain therapeutic levels of drugs for a long period. Biodegradable nanofibers can modulate drug release in addition to allowing the incorporation of fragile bioactive substances. The present work aimed the development of biodegradable intravitreal implants containing dexamethasone coated with polymeric nanofibers containing bevacizumab as a therapeutic proposal for the treatment of AMD. Nanocoated implants were successfully developed. The characterization of the system, the study of degradation and efficiency of the coating process were evaluated by scanning electron microscopy. The drug release profile was determined by high performance liquid cromatography and the Bradford method. The antiangiogenic activity was determined by the chicken embryo chorioallantoic membrane model. The safety of the formulation was evaluated in rabbit eyes. So far, the system was successfully developed. The study degradation study confirmed the presence of nanofibers on the implant surface for up to 35 days. The degradation study demonstrated the presence of nanofibers on the surface of the implant for up to 35 days. The release profile showed that 68% of dexamethasone was released within 35 days and 90% of bevacizumab within 48 hours. The formulation presented activity in reducing vessels and was safe for the rabbits’ retina. No clinical or histopathological changes were observed, neither alteration in retinal thickness by optical coherence tomography during the 28 days. The developed implants, therefore, may be considered as a new alternative for the treatment of AMD. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-04-28T11:11:01Z |
dc.date.available.fl_str_mv |
2023-04-28T11:11:01Z |
dc.date.issued.fl_str_mv |
2023-04-04 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
GUERRA, M. C. A. Dispositivo de liberação intravítrea para tratamento de degeneração macular relacionada à idade. 2023. 122 f. Tese (Doutorado em Nanotecnologia Farmacêutica em Rede) - Universidade Federal de Goiás, Belo Horizonte, 2023. |
dc.identifier.uri.fl_str_mv |
http://repositorio.bc.ufg.br/tede/handle/tede/12794 |
identifier_str_mv |
GUERRA, M. C. A. Dispositivo de liberação intravítrea para tratamento de degeneração macular relacionada à idade. 2023. 122 f. Tese (Doutorado em Nanotecnologia Farmacêutica em Rede) - Universidade Federal de Goiás, Belo Horizonte, 2023. |
url |
http://repositorio.bc.ufg.br/tede/handle/tede/12794 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.program.fl_str_mv |
77 |
dc.relation.confidence.fl_str_mv |
500 500 500 500 |
dc.relation.department.fl_str_mv |
22 |
dc.relation.cnpq.fl_str_mv |
952 |
dc.relation.sponsorship.fl_str_mv |
5 |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.publisher.program.fl_str_mv |
Programa de Pós-graduação em Nanotecnologia Farmacêutica em Rede (FF) |
dc.publisher.initials.fl_str_mv |
UFG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Faculdade de Farmácia - FF (RMG) |
publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFG instname:Universidade Federal de Goiás (UFG) instacron:UFG |
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Universidade Federal de Goiás (UFG) |
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UFG |
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