Nanoesferas poliméricas mucoadesivas associadas aos ácidos cafeico e ferúlico: caracterização, estudo de estabilidade, potencial antioxidante e segurança
Ano de defesa: | 2023 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Centro de Ciências da Saúde |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências Farmacêuticas
|
Departamento: |
Farmácia
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/30074 |
Resumo: | Oral mucositis is characterized by the appearance of erythematous and ulcerative lesions in the oral cavity induced by chemotherapies and radiotherapies, that damage on basal layer of the tissues lead to the expression of pro-inflammatory, pro-apoptotic cytokines and reactive oxygen species (ROS) capable of compromising cellular DNA and triggering other processes of cell apoptosis in the other layers of the epithelium. At low levels, oxidative stress induced by ROS can be prevented through the action of antioxidants. In this context, phenolic compounds have stood out for their property of reducing inflammatory response and potent antioxidant action through the reduction of RSOs. The oral administration of active pharmaceutical ingredients is an alternative in the treatment of oral lesions, being more effective when associated to mucoadhesive formulations. In this sense, polymeric nanoparticles arise, colloidal systems capable of promoting adhesiveness between the body mucosa and its polymers, increasing the retention time of the formulations in the therapeutic target and, consequently, the bioavailability of the compounds. The present work aimed to develop suspensions of cationic nanospheres containing caffeic acid (CA) and ferulic acid (FA) associated, with adequate physicochemical characteristics and potential for incorporation into final pharmaceutical forms. To do this, the antioxidant activity of the suspensions was evaluated by ABTS and DPPH. The photostability of the systems was analyzed, identifying the degradation products formed, as well as assays of mucoadhesion, irritative potential (HET-CAM) and cell viability (murine 3T3 fibroblasts). In addition to developing and validating an analytical methodology for quantification by CLAE. The nanospheres were obtained by the nanoprecipitation method. For physicochemical characterization the following parameters were analyzed: macroscopic analysis, pH values, average particle diameter and polydispersity (photon correlation spectroscopy), zeta potential (electrophoretic mobility). The determination of the content of the compounds and encapsulation efficiency by CLAE method and morphological analysis by atomic force microscopy. The in-vitro release was performed by the diffusion method in dialysis bags and the photostability test was performed with exposure to UVA radiation (365 nm). During the execution of this work, a promising suspension of nanospheres with homogeneous particle size, encapsulation efficiency (>60%), morphology, positive zeta potential and suitable pH was obtained. The nanoparticles showed bioadhesive capacity in the mucoadhesion assay, besides maintaining antioxidant activity and decreasing the irritation potential of the compounds. In the photodegradation assay, it was possible to observe a protective effect of the nanospheres on the phenolic compounds. This work evaluated, in an unprecedented character, the trans-cis isomerization of CA and FA promoted by exposure to UV radiation. The analytical methodology validated for quantification of phenolic compounds proved to be able to quantify both CA and FA simultaneously. In view of the above, nanoformulations containing coencapsulated phenolic acids show promise for future therapeutic application and incorporation into pharmaceutical forms for oral use. |
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2023-08-24T18:39:53Z2023-08-24T18:39:53Z2023-07-05http://repositorio.ufsm.br/handle/1/30074Oral mucositis is characterized by the appearance of erythematous and ulcerative lesions in the oral cavity induced by chemotherapies and radiotherapies, that damage on basal layer of the tissues lead to the expression of pro-inflammatory, pro-apoptotic cytokines and reactive oxygen species (ROS) capable of compromising cellular DNA and triggering other processes of cell apoptosis in the other layers of the epithelium. At low levels, oxidative stress induced by ROS can be prevented through the action of antioxidants. In this context, phenolic compounds have stood out for their property of reducing inflammatory response and potent antioxidant action through the reduction of RSOs. The oral administration of active pharmaceutical ingredients is an alternative in the treatment of oral lesions, being more effective when associated to mucoadhesive formulations. In this sense, polymeric nanoparticles arise, colloidal systems capable of promoting adhesiveness between the body mucosa and its polymers, increasing the retention time of the formulations in the therapeutic target and, consequently, the bioavailability of the compounds. The present work aimed to develop suspensions of cationic nanospheres containing caffeic acid (CA) and ferulic acid (FA) associated, with adequate physicochemical characteristics and potential for incorporation into final pharmaceutical forms. To do this, the antioxidant activity of the suspensions was evaluated by ABTS and DPPH. The photostability of the systems was analyzed, identifying the degradation products formed, as well as assays of mucoadhesion, irritative potential (HET-CAM) and cell viability (murine 3T3 fibroblasts). In addition to developing and validating an analytical methodology for quantification by CLAE. The nanospheres were obtained by the nanoprecipitation method. For physicochemical characterization the following parameters were analyzed: macroscopic analysis, pH values, average particle diameter and polydispersity (photon correlation spectroscopy), zeta potential (electrophoretic mobility). The determination of the content of the compounds and encapsulation efficiency by CLAE method and morphological analysis by atomic force microscopy. The in-vitro release was performed by the diffusion method in dialysis bags and the photostability test was performed with exposure to UVA radiation (365 nm). During the execution of this work, a promising suspension of nanospheres with homogeneous particle size, encapsulation efficiency (>60%), morphology, positive zeta potential and suitable pH was obtained. The nanoparticles showed bioadhesive capacity in the mucoadhesion assay, besides maintaining antioxidant activity and decreasing the irritation potential of the compounds. In the photodegradation assay, it was possible to observe a protective effect of the nanospheres on the phenolic compounds. This work evaluated, in an unprecedented character, the trans-cis isomerization of CA and FA promoted by exposure to UV radiation. The analytical methodology validated for quantification of phenolic compounds proved to be able to quantify both CA and FA simultaneously. In view of the above, nanoformulations containing coencapsulated phenolic acids show promise for future therapeutic application and incorporation into pharmaceutical forms for oral use.A mucosite oral é caracterizada pelo surgimento de lesões eritematosas e ulcerativas na cavidade oral induzidas pelas quimioterapias e radioterapias, o dano na camada basal dos tecidos leva à expressão de citocinas pró-inflamatórias, pró-apoptóticas e espécies reativas de oxigênio (EROs) capazes de comprometer o DNA celular e desencadear outros processos de apoptose celular nas demais camadas do epitélio. Em níveis baixos, o estresse oxidativo induzido pelas EROs pode ser prevenido através da ação de antioxidantes. Neste contexto, os compostos fenólicos têm se destacado por sua propriedade de redução da resposta inflamatória e potente ação antioxidante através da redução de EROs. A administração bucal de insumos farmacêuticos ativos é uma alternativa no tratamento de lesões orais, sendo mais eficaz quando associada a formulações mucoadesivas. Neste sentido, surgem as nanopartículas poliméricas, sistemas coloidais capazes de promover adesividade entre as mucosas do corpo e seus polímeros, aumentando o tempo de retenção das formulações no alvo terapêutico e, por consequência, a biodisponibilidade dos compostos. O presente trabalho teve como objetivo desenvolver suspensões de nanoesferas catiônicas contendo ácido cafeico (CA) e ácido ferúlico (FA) associados, com adequadas características físico-químicas e potencial para a incorporação em formas farmacêuticas finais. Para isso foi avaliada a atividade antioxidante das suspensões por ABTS e DPPH. Analisado a fotodegradação dos sistemas, identificando os produtos de degradação formados, bem como ensaios de mucoadesão, potencial irritativo (HET-CAM) e viabilidade celular (fibroblastos murinos 3T3). Além de desenvolver e validar uma metodologia analítica de quantificação por CLAE. As nanoesferas foram obtidas pelo método de nanoprecipitação. Para caracterização físico-química foram analisados os seguintes parâmetros: análise macroscópica, valor de pH, diâmetro médio das partículas e polidispersão (espectroscopia de correlação de fótons), potencial zeta (mobilidade eletroforética). A determinação do teor dos compostos e eficiência de encapsulamento pelo método CLAE e análise morfológica por microscopia de força atômica. A liberação in-vitro foi realizada pelo método de difusão em sacos de diálise e o ensaio de fotoestabilidade por exposição das amostras à radiação UVA (365 nm). Durante a execução deste trabalho, obteve-se uma promissora suspensão de nanoesferas com tamanho de partículas homogêneo, eficiência de encapsulamento (>60%), morfologia, potencial zeta positivo e pH adequados. As nanopartículas demonstraram capacidade bioadesiva no ensaio de mucoadesão, além de manter a atividade antioxidante e diminuir o potencial de irritação dos compostos. No ensaio de fotodegradação, foi possível observar um efeito protetivo das nanoesferas sobre os compostos fenólicos. Este trabalho avaliou, em caráter inédito, a isomerização trans-cis de CA e FA promovida pela exposição à radiação UV. A metodologia analítica de quantificação dos compostos fenólicos validada mostrou-se capaz de quantificar CA e FA simultaneamente. Frente ao exposto, as nanoformulações contendo ácidos fenólicos coencapsulados mostram-se promissoras para uma futura aplicação terapêutica e incorporação a formas farmacêuticas de uso bucal.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em Ciências FarmacêuticasUFSMBrasilFarmáciaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessEudragit® RL100NanopartículasFotoestabilidadeCompostos fenólicosMucositeNanoparticlesPhotodegradationPhenolic compoundsMucositisCNPQ::CIENCIAS DA SAUDE::FARMACIANanoesferas poliméricas mucoadesivas associadas aos ácidos cafeico e ferúlico: caracterização, estudo de estabilidade, potencial antioxidante e segurançaMucoadhesive polymeric nanospheres associated with caffeic and ferulic acids: characterization, stability study, antioxidant potential and safetyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisSilva, Cristiane de Bona dahttp://lattes.cnpq.br/6029111646602279Schaffazick , Scheila RezendeRolim, Clarice Madalena BuenoGarcia, Cássia Virgíniahttp://lattes.cnpq.br/7946164394089996Felix, Igor Roesch40030000000560060060060060060077eeaef8-05f4-4cee-b949-c09342e7eb61dabf9718-7537-4250-b6d9-18cb67a4c96bb4edad2c-f8f7-476f-9b85-237b01c5eceda3d69349-9d61-4cb0-a5c9-60c0234931edb9047891-4d69-4410-a916-462a8a2df37breponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGCF_2023_FELIX_IGOR.pdfDIS_PPGCF_2023_FELIX_IGOR.pdfDissertação de mestradoapplication/pdf1807296http://repositorio.ufsm.br/bitstream/1/30074/1/DIS_PPGCF_2023_FELIX_IGOR.pdf754108674dd059f464ab7b448bcda011MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Nanoesferas poliméricas mucoadesivas associadas aos ácidos cafeico e ferúlico: caracterização, estudo de estabilidade, potencial antioxidante e segurança |
dc.title.alternative.eng.fl_str_mv |
Mucoadhesive polymeric nanospheres associated with caffeic and ferulic acids: characterization, stability study, antioxidant potential and safety |
title |
Nanoesferas poliméricas mucoadesivas associadas aos ácidos cafeico e ferúlico: caracterização, estudo de estabilidade, potencial antioxidante e segurança |
spellingShingle |
Nanoesferas poliméricas mucoadesivas associadas aos ácidos cafeico e ferúlico: caracterização, estudo de estabilidade, potencial antioxidante e segurança Felix, Igor Roesch Eudragit® RL100 Nanopartículas Fotoestabilidade Compostos fenólicos Mucosite Nanoparticles Photodegradation Phenolic compounds Mucositis CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Nanoesferas poliméricas mucoadesivas associadas aos ácidos cafeico e ferúlico: caracterização, estudo de estabilidade, potencial antioxidante e segurança |
title_full |
Nanoesferas poliméricas mucoadesivas associadas aos ácidos cafeico e ferúlico: caracterização, estudo de estabilidade, potencial antioxidante e segurança |
title_fullStr |
Nanoesferas poliméricas mucoadesivas associadas aos ácidos cafeico e ferúlico: caracterização, estudo de estabilidade, potencial antioxidante e segurança |
title_full_unstemmed |
Nanoesferas poliméricas mucoadesivas associadas aos ácidos cafeico e ferúlico: caracterização, estudo de estabilidade, potencial antioxidante e segurança |
title_sort |
Nanoesferas poliméricas mucoadesivas associadas aos ácidos cafeico e ferúlico: caracterização, estudo de estabilidade, potencial antioxidante e segurança |
author |
Felix, Igor Roesch |
author_facet |
Felix, Igor Roesch |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Silva, Cristiane de Bona da |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6029111646602279 |
dc.contributor.advisor-co1.fl_str_mv |
Schaffazick , Scheila Rezende |
dc.contributor.referee1.fl_str_mv |
Rolim, Clarice Madalena Bueno |
dc.contributor.referee2.fl_str_mv |
Garcia, Cássia Virgínia |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/7946164394089996 |
dc.contributor.author.fl_str_mv |
Felix, Igor Roesch |
contributor_str_mv |
Silva, Cristiane de Bona da Schaffazick , Scheila Rezende Rolim, Clarice Madalena Bueno Garcia, Cássia Virgínia |
dc.subject.por.fl_str_mv |
Eudragit® RL100 Nanopartículas Fotoestabilidade Compostos fenólicos Mucosite |
topic |
Eudragit® RL100 Nanopartículas Fotoestabilidade Compostos fenólicos Mucosite Nanoparticles Photodegradation Phenolic compounds Mucositis CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Nanoparticles Photodegradation Phenolic compounds Mucositis |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Oral mucositis is characterized by the appearance of erythematous and ulcerative lesions in the oral cavity induced by chemotherapies and radiotherapies, that damage on basal layer of the tissues lead to the expression of pro-inflammatory, pro-apoptotic cytokines and reactive oxygen species (ROS) capable of compromising cellular DNA and triggering other processes of cell apoptosis in the other layers of the epithelium. At low levels, oxidative stress induced by ROS can be prevented through the action of antioxidants. In this context, phenolic compounds have stood out for their property of reducing inflammatory response and potent antioxidant action through the reduction of RSOs. The oral administration of active pharmaceutical ingredients is an alternative in the treatment of oral lesions, being more effective when associated to mucoadhesive formulations. In this sense, polymeric nanoparticles arise, colloidal systems capable of promoting adhesiveness between the body mucosa and its polymers, increasing the retention time of the formulations in the therapeutic target and, consequently, the bioavailability of the compounds. The present work aimed to develop suspensions of cationic nanospheres containing caffeic acid (CA) and ferulic acid (FA) associated, with adequate physicochemical characteristics and potential for incorporation into final pharmaceutical forms. To do this, the antioxidant activity of the suspensions was evaluated by ABTS and DPPH. The photostability of the systems was analyzed, identifying the degradation products formed, as well as assays of mucoadhesion, irritative potential (HET-CAM) and cell viability (murine 3T3 fibroblasts). In addition to developing and validating an analytical methodology for quantification by CLAE. The nanospheres were obtained by the nanoprecipitation method. For physicochemical characterization the following parameters were analyzed: macroscopic analysis, pH values, average particle diameter and polydispersity (photon correlation spectroscopy), zeta potential (electrophoretic mobility). The determination of the content of the compounds and encapsulation efficiency by CLAE method and morphological analysis by atomic force microscopy. The in-vitro release was performed by the diffusion method in dialysis bags and the photostability test was performed with exposure to UVA radiation (365 nm). During the execution of this work, a promising suspension of nanospheres with homogeneous particle size, encapsulation efficiency (>60%), morphology, positive zeta potential and suitable pH was obtained. The nanoparticles showed bioadhesive capacity in the mucoadhesion assay, besides maintaining antioxidant activity and decreasing the irritation potential of the compounds. In the photodegradation assay, it was possible to observe a protective effect of the nanospheres on the phenolic compounds. This work evaluated, in an unprecedented character, the trans-cis isomerization of CA and FA promoted by exposure to UV radiation. The analytical methodology validated for quantification of phenolic compounds proved to be able to quantify both CA and FA simultaneously. In view of the above, nanoformulations containing coencapsulated phenolic acids show promise for future therapeutic application and incorporation into pharmaceutical forms for oral use. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-08-24T18:39:53Z |
dc.date.available.fl_str_mv |
2023-08-24T18:39:53Z |
dc.date.issued.fl_str_mv |
2023-07-05 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/30074 |
url |
http://repositorio.ufsm.br/handle/1/30074 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
400300000005 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 600 |
dc.relation.authority.fl_str_mv |
77eeaef8-05f4-4cee-b949-c09342e7eb61 dabf9718-7537-4250-b6d9-18cb67a4c96b b4edad2c-f8f7-476f-9b85-237b01c5eced a3d69349-9d61-4cb0-a5c9-60c0234931ed b9047891-4d69-4410-a916-462a8a2df37b |
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 Santa Maria Centro de Ciências da Saúde |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Farmacêuticas |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Farmácia |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações do UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Biblioteca Digital de Teses e Dissertações do UFSM |
collection |
Biblioteca Digital de Teses e Dissertações do UFSM |
bitstream.url.fl_str_mv |
http://repositorio.ufsm.br/bitstream/1/30074/1/DIS_PPGCF_2023_FELIX_IGOR.pdf http://repositorio.ufsm.br/bitstream/1/30074/2/license_rdf http://repositorio.ufsm.br/bitstream/1/30074/3/license.txt |
bitstream.checksum.fl_str_mv |
754108674dd059f464ab7b448bcda011 4460e5956bc1d1639be9ae6146a50347 2f0571ecee68693bd5cd3f17c1e075df |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1793240103871578112 |