Hidrogéis de goma de alfarroba contendo compostos indólicos nanoencapsulados com ação anti-inflamatória em desordens cutâneas induzidas em camundongos
Ano de defesa: | 2019 |
---|---|
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: |
Análises Clínicas e Toxicológicas
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/22354 |
Resumo: | The skin is constantly exposed to external stimuli, such as irritants substances and ultraviolet radiation type B (UVB), which can trigger an inflammatory response. Indole-3-carbinol (I3C) and 3-3'-diindolmethane (DIM) are obtained by the hydrolysis of glycobrassicin, present in plants of the genus Brassica, and its anti-inflammatory effects have already been reported. However, they present physicochemical limitations that hinder their therapeutic use. Thus, in studies carried out in our research group, nanocapsule suspensions containing I3C or DIM were developed. Nanotechnology within the scope of topical application has provided numerous benefits such as: modulation of permeation/penetration/retention of substances in the cutaneous tissue. Aimed at cutaneous application, this dissertation aimed to develop hydrogels as a vehicle for nanocapsules containing I3C or DIM and check their potential against two models of skin inflammation. The hydrogels were prepared from the thickening of the nanocapsule suspensions with locust bean gum (3%). The formulations developed presented physicochemical characteristics suitable for cutaneous application, maintaining the nanometer size in the range of 138-231 nm (photon correlation spectroscopy), active content close to the theoretical value (0.5 mg/g for I3C hydrogels and 1.0 mg/g for DIM hydrogels (CLAE), pH values in the neutral range 6.69-7.43 (potentiometry), as well as non-Newtonian pseudoplastic behavior (rotational viscometer). For the release studies of the active from the hydrogel and skin permeation through human skin, Franz cell apparatus was used. The in vitro release demonstrated that the nanocapsules can easily leave the semisolid vehicle, whereas the study of skin permeation showed that nanoencapsulation promoted a greater retention of the active in the stratum corneum and epidermis, suggesting that the stratum corneum can act as deposit for their release. The evaluation of the irritation potential by the HET-CAM method indicated no bleeding, coagulation or lysis of the vessels present in the membrane, demonstrating that the formulations are considered non-irritating. Furthermore, nanoencapsulation protected the I3C from photodegradation induced by UVC radiation. Finally, the performance of the formulations was evaluated in two in vivo models of cutaneous inflammation, one induced by croton oil and the other by UVB radiation. In the croton oil model both the hydrogels containing the nanocapsules and the hydrogels containing the free actives were able to act by expressively reducing ear edema and inflammatory cells. The UVB radiation experiment demonstrated that formulations containing the free or nanoencapsulated actives were effective in reducing mouse ear edema and leukocyte infiltration within 24 h. In 48 h, only the hydrogels containing the nanoencapsulated actives maintained the antidematogenic effect, indicating a prolonged effect of the nanocapsules. Thus, it can be concluded that the developed hydrogels are promising in the treatment of inflammatory skin disorders, modulating the cutaneous distribution of the active substances in the layers of interest, besides being considered non-irritating for dermatological use. |
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2021-10-07T18:01:17Z2021-10-07T18:01:17Z2019-03-29http://repositorio.ufsm.br/handle/1/22354The skin is constantly exposed to external stimuli, such as irritants substances and ultraviolet radiation type B (UVB), which can trigger an inflammatory response. Indole-3-carbinol (I3C) and 3-3'-diindolmethane (DIM) are obtained by the hydrolysis of glycobrassicin, present in plants of the genus Brassica, and its anti-inflammatory effects have already been reported. However, they present physicochemical limitations that hinder their therapeutic use. Thus, in studies carried out in our research group, nanocapsule suspensions containing I3C or DIM were developed. Nanotechnology within the scope of topical application has provided numerous benefits such as: modulation of permeation/penetration/retention of substances in the cutaneous tissue. Aimed at cutaneous application, this dissertation aimed to develop hydrogels as a vehicle for nanocapsules containing I3C or DIM and check their potential against two models of skin inflammation. The hydrogels were prepared from the thickening of the nanocapsule suspensions with locust bean gum (3%). The formulations developed presented physicochemical characteristics suitable for cutaneous application, maintaining the nanometer size in the range of 138-231 nm (photon correlation spectroscopy), active content close to the theoretical value (0.5 mg/g for I3C hydrogels and 1.0 mg/g for DIM hydrogels (CLAE), pH values in the neutral range 6.69-7.43 (potentiometry), as well as non-Newtonian pseudoplastic behavior (rotational viscometer). For the release studies of the active from the hydrogel and skin permeation through human skin, Franz cell apparatus was used. The in vitro release demonstrated that the nanocapsules can easily leave the semisolid vehicle, whereas the study of skin permeation showed that nanoencapsulation promoted a greater retention of the active in the stratum corneum and epidermis, suggesting that the stratum corneum can act as deposit for their release. The evaluation of the irritation potential by the HET-CAM method indicated no bleeding, coagulation or lysis of the vessels present in the membrane, demonstrating that the formulations are considered non-irritating. Furthermore, nanoencapsulation protected the I3C from photodegradation induced by UVC radiation. Finally, the performance of the formulations was evaluated in two in vivo models of cutaneous inflammation, one induced by croton oil and the other by UVB radiation. In the croton oil model both the hydrogels containing the nanocapsules and the hydrogels containing the free actives were able to act by expressively reducing ear edema and inflammatory cells. The UVB radiation experiment demonstrated that formulations containing the free or nanoencapsulated actives were effective in reducing mouse ear edema and leukocyte infiltration within 24 h. In 48 h, only the hydrogels containing the nanoencapsulated actives maintained the antidematogenic effect, indicating a prolonged effect of the nanocapsules. Thus, it can be concluded that the developed hydrogels are promising in the treatment of inflammatory skin disorders, modulating the cutaneous distribution of the active substances in the layers of interest, besides being considered non-irritating for dermatological use.A pele está constantemente sujeita a estímulos externos, como substâncias irritantes e radiação ultravioleta do tipo B (UVB), os quais podem desencadear nesta uma resposta inflamatória. O indol-3-carbinol (I3C) e o 3-3’-diindolmetano (DIM) são obtidos através da hidrólise da glicobrassicina, presentes em vegetais do gênero Brassica, e já foram relatados seus efeitos anti-inflamatórios. No entanto, apresentam limitações físico-químicas que dificultam seu emprego terapêutico. Desta forma, em estudos realizados em nosso grupo de pesquisa, foram desenvolvidas suspensões de nanocápsulas contendo I3C ou DIM. A nanotecnologia, no âmbito da aplicação tópica, tem proporcionado inúmeros benefícios, tais como: modulação da permeação/penetração/retenção de substâncias no tecido cutâneo. Visando a aplicação cutânea, essa dissertação objetivou desenvolver hidrogéis para veicular nanocápsulas contendo I3C ou DIM e verificar seu potencial frente a dois modelos de inflamação cutânea. Os hidrogéis foram preparados a partir do espessamento das suspensões de nanocápsulas com a goma de alfarroba (3%). As formulações desenvolvidas apresentaram características físico-químicas adequadas para aplicação cutânea, mantendo o tamanho nanométrico na faixa de 138-231 nm (espectroscopia de correlação de fótons), teor de ativos próximo ao valor teórico (0,5 mg/g para hidrogéis de I3C e 1,0 mg/g para hidrogéis de DIM) (CLAE), valores de pH na faixa da neutralidade 6,69-7,43 (potenciometria), assim como comportamento não-newtoniano pseudo-plástico (viscosímetro rotacional). Para os estudos de liberação dos ativos a partir dos hidrogéis e permeação cutânea em pele humana utilizou-se células de Franz. A liberação in vitro demonstrou que as nanocápsulas conseguem deixar facilmente a base semissólida, enquanto que o estudo de permeação cutânea evidenciou que a nanoencapsulação promoveu uma maior retenção dos ativos no estrato córneo e epiderme, sugerindo assim que o estrato córneo pode funcionar como depósito para liberação gradual destes. A avaliação do potencial de irritação pelo método de HET-CAM indicou ausência de hemorragia, coagulação ou lise dos vasos presentes na membrana, demonstrando que as formulações são consideradas não-irritantes. Ainda, a nanoencapsulação protegeu o I3C da fotodegradação induzida pela radiação UVC. Por fim, avaliou-se o desempenho das formulações em dois modelos in vivo de inflamação cutânea, um induzido pelo óleo de cróton e outro pela radiação UVB. No modelo do óleo de cróton, tanto os hidrogéis contendo as nanocápsulas, quanto as respectivas formulações contendo os ativos livres foram capazes de atuar reduzindo expressivamente o edema de orelha e as células inflamatórias. O experimento da radiação UVB demonstrou que as formulações contendo os ativos livres ou nanoencapsulados foram eficazes na redução do edema da orelha de camundongos e infiltração de leucócitos em 24 h. Em 48 h, apenas os hidrogéis contendo os ativos nanoencapsulados mantiveram o efeito antiedematogênico, indicando um efeito prolongado das nanocápsulas. Assim, pode-se concluir que os hidrogéis desenvolvidos são promissores no tratamento de desordens inflamatórias de pele, modulam a distribuição cutânea dos ativos nas camadas de interesse, além de serem considerados não-irritantes para o uso dermatológico.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em Ciências FarmacêuticasUFSMBrasilAnálises Clínicas e ToxicológicasAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessNanopartículasSemissólidosIndol-3-carbinolAdministração cutâneaInflamaçãoNanoparticlesSemisolidsCutaneous administrationInflammationCNPQ::CIENCIAS DA SAUDE::FARMACIAHidrogéis de goma de alfarroba contendo compostos indólicos nanoencapsulados com ação anti-inflamatória em desordens cutâneas induzidas em camundongosLocust bean gum hydrogels containing nanoencapsulated indolic compounds with anti-inflammatory action in cutaneous disorders induced in miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisCruz, Letíciahttp://lattes.cnpq.br/3095970241017527Bochi, Guilherme VargasContri, Renata Vidorhttp://lattes.cnpq.br/4720936761244894Giuliani, Laura Minussi4003000000056006006006000386aa43-4a59-457e-af9d-d69296d839f83294fcbc-53d7-4ed3-a00e-0e41dd7585566e2ef066-1dbd-42a0-9cf7-367e79b50354df70ae95-34d1-43a4-9bb1-22b981255cb7reponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Hidrogéis de goma de alfarroba contendo compostos indólicos nanoencapsulados com ação anti-inflamatória em desordens cutâneas induzidas em camundongos |
dc.title.alternative.eng.fl_str_mv |
Locust bean gum hydrogels containing nanoencapsulated indolic compounds with anti-inflammatory action in cutaneous disorders induced in mice |
title |
Hidrogéis de goma de alfarroba contendo compostos indólicos nanoencapsulados com ação anti-inflamatória em desordens cutâneas induzidas em camundongos |
spellingShingle |
Hidrogéis de goma de alfarroba contendo compostos indólicos nanoencapsulados com ação anti-inflamatória em desordens cutâneas induzidas em camundongos Giuliani, Laura Minussi Nanopartículas Semissólidos Indol-3-carbinol Administração cutânea Inflamação Nanoparticles Semisolids Cutaneous administration Inflammation CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Hidrogéis de goma de alfarroba contendo compostos indólicos nanoencapsulados com ação anti-inflamatória em desordens cutâneas induzidas em camundongos |
title_full |
Hidrogéis de goma de alfarroba contendo compostos indólicos nanoencapsulados com ação anti-inflamatória em desordens cutâneas induzidas em camundongos |
title_fullStr |
Hidrogéis de goma de alfarroba contendo compostos indólicos nanoencapsulados com ação anti-inflamatória em desordens cutâneas induzidas em camundongos |
title_full_unstemmed |
Hidrogéis de goma de alfarroba contendo compostos indólicos nanoencapsulados com ação anti-inflamatória em desordens cutâneas induzidas em camundongos |
title_sort |
Hidrogéis de goma de alfarroba contendo compostos indólicos nanoencapsulados com ação anti-inflamatória em desordens cutâneas induzidas em camundongos |
author |
Giuliani, Laura Minussi |
author_facet |
Giuliani, Laura Minussi |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Cruz, Letícia |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/3095970241017527 |
dc.contributor.referee1.fl_str_mv |
Bochi, Guilherme Vargas |
dc.contributor.referee2.fl_str_mv |
Contri, Renata Vidor |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4720936761244894 |
dc.contributor.author.fl_str_mv |
Giuliani, Laura Minussi |
contributor_str_mv |
Cruz, Letícia Bochi, Guilherme Vargas Contri, Renata Vidor |
dc.subject.por.fl_str_mv |
Nanopartículas Semissólidos Indol-3-carbinol Administração cutânea Inflamação |
topic |
Nanopartículas Semissólidos Indol-3-carbinol Administração cutânea Inflamação Nanoparticles Semisolids Cutaneous administration Inflammation CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Nanoparticles Semisolids Cutaneous administration Inflammation |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
The skin is constantly exposed to external stimuli, such as irritants substances and ultraviolet radiation type B (UVB), which can trigger an inflammatory response. Indole-3-carbinol (I3C) and 3-3'-diindolmethane (DIM) are obtained by the hydrolysis of glycobrassicin, present in plants of the genus Brassica, and its anti-inflammatory effects have already been reported. However, they present physicochemical limitations that hinder their therapeutic use. Thus, in studies carried out in our research group, nanocapsule suspensions containing I3C or DIM were developed. Nanotechnology within the scope of topical application has provided numerous benefits such as: modulation of permeation/penetration/retention of substances in the cutaneous tissue. Aimed at cutaneous application, this dissertation aimed to develop hydrogels as a vehicle for nanocapsules containing I3C or DIM and check their potential against two models of skin inflammation. The hydrogels were prepared from the thickening of the nanocapsule suspensions with locust bean gum (3%). The formulations developed presented physicochemical characteristics suitable for cutaneous application, maintaining the nanometer size in the range of 138-231 nm (photon correlation spectroscopy), active content close to the theoretical value (0.5 mg/g for I3C hydrogels and 1.0 mg/g for DIM hydrogels (CLAE), pH values in the neutral range 6.69-7.43 (potentiometry), as well as non-Newtonian pseudoplastic behavior (rotational viscometer). For the release studies of the active from the hydrogel and skin permeation through human skin, Franz cell apparatus was used. The in vitro release demonstrated that the nanocapsules can easily leave the semisolid vehicle, whereas the study of skin permeation showed that nanoencapsulation promoted a greater retention of the active in the stratum corneum and epidermis, suggesting that the stratum corneum can act as deposit for their release. The evaluation of the irritation potential by the HET-CAM method indicated no bleeding, coagulation or lysis of the vessels present in the membrane, demonstrating that the formulations are considered non-irritating. Furthermore, nanoencapsulation protected the I3C from photodegradation induced by UVC radiation. Finally, the performance of the formulations was evaluated in two in vivo models of cutaneous inflammation, one induced by croton oil and the other by UVB radiation. In the croton oil model both the hydrogels containing the nanocapsules and the hydrogels containing the free actives were able to act by expressively reducing ear edema and inflammatory cells. The UVB radiation experiment demonstrated that formulations containing the free or nanoencapsulated actives were effective in reducing mouse ear edema and leukocyte infiltration within 24 h. In 48 h, only the hydrogels containing the nanoencapsulated actives maintained the antidematogenic effect, indicating a prolonged effect of the nanocapsules. Thus, it can be concluded that the developed hydrogels are promising in the treatment of inflammatory skin disorders, modulating the cutaneous distribution of the active substances in the layers of interest, besides being considered non-irritating for dermatological use. |
publishDate |
2019 |
dc.date.issued.fl_str_mv |
2019-03-29 |
dc.date.accessioned.fl_str_mv |
2021-10-07T18:01:17Z |
dc.date.available.fl_str_mv |
2021-10-07T18:01:17Z |
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/1/22354 |
url |
http://repositorio.ufsm.br/handle/1/22354 |
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 |
dc.relation.authority.fl_str_mv |
0386aa43-4a59-457e-af9d-d69296d839f8 3294fcbc-53d7-4ed3-a00e-0e41dd758556 6e2ef066-1dbd-42a0-9cf7-367e79b50354 df70ae95-34d1-43a4-9bb1-22b981255cb7 |
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 |
Análises Clínicas e Toxicológicas |
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 |
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MD5 MD5 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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1793240174182793216 |