Hidrogel de goma de alfarroba contendo nanocápsulas de disseleneto de difenila para o tratamento da tricomoníase vaginal
Ano de defesa: | 2021 |
---|---|
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: |
Desenvolvimento e Avaliação de Produtos Farmacêuticos
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/23624 |
Resumo: | Trichomoniasis is a sexually transmitted infection (IST) whose vector is the parasite Trichomonas vaginalis. Conventional therapies have, in most cases, low efficacy and high toxicity, making the search for new therapies relevant. Diphenyl diselenide (PhSe)2, is an organic selenium compound with antioxidant, anti-inflammatory properties, in addition to activity against some microorganisms. However, this compound has high lipophilicity and toxic effects, which makes its clinical use difficult. In this sense, polymeric nanocapsules become an interesting alternative to overcome its limitations. Therefore, this dissertation aimed to develop nanocapsule suspensions of Eudragit® RS100 and coconut oil containing (PhSe)2 and to evaluate, in an unprecedented way, its anti-trichomonas activity, in addition to investigating the feasibility of preparing a hydrogel with this suspension, using locust bean gum as a gel-forming agent, aiming at vaginal application for the treatment of trichomoniasis. The nanocapsule suspensions were prepared by the preformed polymer interfacial deposition method and characteristics compatible with nanostructured drug delivery systems were observed, such as average particle size in the nanometric range (193-206 nm), adequate polydispersion index (0.19-0.22), positive zeta potential, pH in the acidic range (4.97-5.04), compound content close to theoretical value (1.04 mg/mL), and high encapsulation efficiency (99.92 %). In the evaluation of the in vitro activity in cells infected by T. vaginalis, (PhSe)2 nanoencapsulated at intermediate concentrations reduced the viability of the trophozoite more significantly compared to the free form of the active, due to controlled release provided by the nanocarrier system. The antioxidant capacity of nanoencapsulated (PhSe)2 was superior to the free form. The mucoadhesion evaluation of the nanocapsules, with change in the average diameter and the inversion of the zeta potential, confirmed their mucoadhesive potential, attributed to the cationic polymer. The hydrogels were prepared by thickening the nanocapsule suspensions with locust bean gum (3%). The developed formulations presented physicochemical characteristics suitable for vaginal application, maintaining the nanometer size in the range of 237-295 nm (photon correlation spectroscopy), active content close to the theoretical value (1mg/g of (PhSe)2) (HPLC), pH values in the neutrality range 6.16-6.20 (potentiometry), as well as non-Newtonian pseudo-plastic behavior (rotational viscometer). The evaluation of the irritation potential by the chorioallantoic membrane method indicated the absence of hemorrhage, coagulation or lysis, demonstrating that the formulations are considered non-irritating. The mucoadhesive strength of hydrogels was improved for the nanoencapsulated active compared to the free (PhSe)2, demonstrating the correct choice of gum. Permeation through the bovine vaginal mucosa using Franz cells showed that the formulations remained on the surface of the vaginal mucosa, which is ideal for the treatment of superficial vaginal infections. Therefore, based on the results obtained, the development of the hydrogel met the proposed therapeutic purpose and could be a promising alternative for the treatment of trichomoniasis. |
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2022-01-27T19:44:53Z2022-01-27T19:44:53Z2021-09-27http://repositorio.ufsm.br/handle/1/23624Trichomoniasis is a sexually transmitted infection (IST) whose vector is the parasite Trichomonas vaginalis. Conventional therapies have, in most cases, low efficacy and high toxicity, making the search for new therapies relevant. Diphenyl diselenide (PhSe)2, is an organic selenium compound with antioxidant, anti-inflammatory properties, in addition to activity against some microorganisms. However, this compound has high lipophilicity and toxic effects, which makes its clinical use difficult. In this sense, polymeric nanocapsules become an interesting alternative to overcome its limitations. Therefore, this dissertation aimed to develop nanocapsule suspensions of Eudragit® RS100 and coconut oil containing (PhSe)2 and to evaluate, in an unprecedented way, its anti-trichomonas activity, in addition to investigating the feasibility of preparing a hydrogel with this suspension, using locust bean gum as a gel-forming agent, aiming at vaginal application for the treatment of trichomoniasis. The nanocapsule suspensions were prepared by the preformed polymer interfacial deposition method and characteristics compatible with nanostructured drug delivery systems were observed, such as average particle size in the nanometric range (193-206 nm), adequate polydispersion index (0.19-0.22), positive zeta potential, pH in the acidic range (4.97-5.04), compound content close to theoretical value (1.04 mg/mL), and high encapsulation efficiency (99.92 %). In the evaluation of the in vitro activity in cells infected by T. vaginalis, (PhSe)2 nanoencapsulated at intermediate concentrations reduced the viability of the trophozoite more significantly compared to the free form of the active, due to controlled release provided by the nanocarrier system. The antioxidant capacity of nanoencapsulated (PhSe)2 was superior to the free form. The mucoadhesion evaluation of the nanocapsules, with change in the average diameter and the inversion of the zeta potential, confirmed their mucoadhesive potential, attributed to the cationic polymer. The hydrogels were prepared by thickening the nanocapsule suspensions with locust bean gum (3%). The developed formulations presented physicochemical characteristics suitable for vaginal application, maintaining the nanometer size in the range of 237-295 nm (photon correlation spectroscopy), active content close to the theoretical value (1mg/g of (PhSe)2) (HPLC), pH values in the neutrality range 6.16-6.20 (potentiometry), as well as non-Newtonian pseudo-plastic behavior (rotational viscometer). The evaluation of the irritation potential by the chorioallantoic membrane method indicated the absence of hemorrhage, coagulation or lysis, demonstrating that the formulations are considered non-irritating. The mucoadhesive strength of hydrogels was improved for the nanoencapsulated active compared to the free (PhSe)2, demonstrating the correct choice of gum. Permeation through the bovine vaginal mucosa using Franz cells showed that the formulations remained on the surface of the vaginal mucosa, which is ideal for the treatment of superficial vaginal infections. Therefore, based on the results obtained, the development of the hydrogel met the proposed therapeutic purpose and could be a promising alternative for the treatment of trichomoniasis.A tricomoníase é uma infecção sexualmente transmissível (IST) que tem como vetor o parasita Trichomonas vaginalis. As terapias convencionais apresentam na maioria dos casos uma baixa eficácia e elevada toxicidade, sendo relevante a busca por novas terapias. O Disseleneto de Difenila (PhSe)2 é um composto orgânico de selênio com propriedades antioxidante, antiinflamatória, além de atividade frente a alguns microorganismos. Porém, este composto apresenta elevada lipofilia e efeitos tóxicos, o que dificulta seu uso clínico. Nesse sentido, as nanocápsulas poliméricas tornam-se uma alternativa interessante para contornar as limitações do (PhSe)2. Diante disso, esta dissertação teve como objetivo desenvolver suspensões de nanocápsulas de Eudragit® RS100 e óleo de coco contendo (PhSe)2 e avaliar, de forma inédita, sua atividade anti-trichomonas, além de investigar a viabilidade da preparação de um hidrogel contendo as nanocápsulas, utilizando a goma de alfarroba como agente formador de gel, visando a aplicação vaginal. As suspensões de nanocápsulas foram preparadas pelo método de deposição interfacial do polímero pré-formado e foram observadas características compatíveis com sistemas nanoestruturados para liberação de fármacos, como tamanho médio de partícula na faixa nanométrica (193-206 nm), índice de polidispersão adequado (0,19-0,22), potencial zeta positivo, pH na faixa ácida (4,97-5,04), teor do composto próximo ao valor teórico (1,04 mg/mL), e elevada eficiência de encapsulamento (99,92 %). Na avaliação da atividade in vitro em células infectadas pelo T. vaginalis, (PhSe)2 nanoencapsulado em concentrações intermediárias, reduziu a viabilidade do trofozoíto de forma mais expressiva em comparação à forma livre do ativo.. A capacidade antioxidante do (PhSe)2 nanoencapsulado foi superior à forma livre. A avaliação do potencial mucoadesivo das nanocápsulas, com alteração do diâmetro médio e a inversão do potencial zeta, comprovou seu potencial mucoadesivo, atribuído ao polímero catiônico. 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 vaginal, mantendo o tamanho nanométrico na faixa de 237-295 nm (espectroscopia de correlação de fótons), teor de ativo próximo ao valor teórico (1mg/g de (PhSe)2) (CLAE), valores de pH próximo à faixa da neutralidade 6,16-6,20 (potenciometria), assim como comportamento reológico não-newtoniano pseudo-plástico (viscosímetro rotacional). A avaliação do potencial de irritação pelo método da membrana corioalantóide indicou ausência de hemorragia, coagulação ou lise, demonstrando que as formulações são consideradas não-irritantes. A força mucoadesiva dos hidrogéis foi aprimorada para o ativo nanoencapsulado em comparação ao (PhSe)2 livre, demonstrando a escolha correta da goma. A permeação através da mucosa vaginal bovina utilizando células de Franz evidenciou que as formulações permaneceram na superfície da mucosa vaginal, o que é ideal para o tratamento de infecções vaginais superficiais. Portanto, baseado nos resultados obtidos, o desenvolvimento do hidrogel atendeu a finalidade terapêutica proposta, podendo ser uma alternativa promissora para o tratamento da tricomoníase.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESConselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqporUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em Ciências FarmacêuticasUFSMBrasilDesenvolvimento e Avaliação de Produtos FarmacêuticosAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessNanopartículasSelênioVia vaginalSemissólidosTrichomonas vaginalisNanoparticlesSeleniumVaginal routeSemisolidsCNPQ::CIENCIAS DA SAUDE::FARMACIAHidrogel de goma de alfarroba contendo nanocápsulas de disseleneto de difenila para o tratamento da tricomoníase vaginalLocust bean gum hydrogel containing diphenyl diselenide nanocapsules for vaginal treatment of trichomoniasisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisCruz, Letíciahttp://lattes.cnpq.br/3095970241017527Ferreira, Luana MotaMenezes, Charlene Cavalheiro dehttp://lattes.cnpq.br/8279690650860280Reis, Fernanda Padoin dos400300000005600600600600600cf7075ca-f0df-4f36-9290-3d918a0c407f8d63e7ef-961b-4097-a5bc-c9ee404b4c7fab6ad53c-7541-4086-a4b0-1773dbcd1d219c45c608-9a3e-435d-b73d-882ea0b87cb8reponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGCF_2021_REIS_FERNANDA.pdfDIS_PPGCF_2021_REIS_FERNANDA.pdfDissertação de Mestradoapplication/pdf2085596http://repositorio.ufsm.br/bitstream/1/23624/1/DIS_PPGCF_2021_REIS_FERNANDA.pdf08e07e80d7632558037f1349ce49e146MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Hidrogel de goma de alfarroba contendo nanocápsulas de disseleneto de difenila para o tratamento da tricomoníase vaginal |
dc.title.alternative.eng.fl_str_mv |
Locust bean gum hydrogel containing diphenyl diselenide nanocapsules for vaginal treatment of trichomoniasis |
title |
Hidrogel de goma de alfarroba contendo nanocápsulas de disseleneto de difenila para o tratamento da tricomoníase vaginal |
spellingShingle |
Hidrogel de goma de alfarroba contendo nanocápsulas de disseleneto de difenila para o tratamento da tricomoníase vaginal Reis, Fernanda Padoin dos Nanopartículas Selênio Via vaginal Semissólidos Trichomonas vaginalis Nanoparticles Selenium Vaginal route Semisolids CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Hidrogel de goma de alfarroba contendo nanocápsulas de disseleneto de difenila para o tratamento da tricomoníase vaginal |
title_full |
Hidrogel de goma de alfarroba contendo nanocápsulas de disseleneto de difenila para o tratamento da tricomoníase vaginal |
title_fullStr |
Hidrogel de goma de alfarroba contendo nanocápsulas de disseleneto de difenila para o tratamento da tricomoníase vaginal |
title_full_unstemmed |
Hidrogel de goma de alfarroba contendo nanocápsulas de disseleneto de difenila para o tratamento da tricomoníase vaginal |
title_sort |
Hidrogel de goma de alfarroba contendo nanocápsulas de disseleneto de difenila para o tratamento da tricomoníase vaginal |
author |
Reis, Fernanda Padoin dos |
author_facet |
Reis, Fernanda Padoin dos |
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 |
Ferreira, Luana Mota |
dc.contributor.referee2.fl_str_mv |
Menezes, Charlene Cavalheiro de |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/8279690650860280 |
dc.contributor.author.fl_str_mv |
Reis, Fernanda Padoin dos |
contributor_str_mv |
Cruz, Letícia Ferreira, Luana Mota Menezes, Charlene Cavalheiro de |
dc.subject.por.fl_str_mv |
Nanopartículas Selênio Via vaginal Semissólidos Trichomonas vaginalis |
topic |
Nanopartículas Selênio Via vaginal Semissólidos Trichomonas vaginalis Nanoparticles Selenium Vaginal route Semisolids CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Nanoparticles Selenium Vaginal route Semisolids |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Trichomoniasis is a sexually transmitted infection (IST) whose vector is the parasite Trichomonas vaginalis. Conventional therapies have, in most cases, low efficacy and high toxicity, making the search for new therapies relevant. Diphenyl diselenide (PhSe)2, is an organic selenium compound with antioxidant, anti-inflammatory properties, in addition to activity against some microorganisms. However, this compound has high lipophilicity and toxic effects, which makes its clinical use difficult. In this sense, polymeric nanocapsules become an interesting alternative to overcome its limitations. Therefore, this dissertation aimed to develop nanocapsule suspensions of Eudragit® RS100 and coconut oil containing (PhSe)2 and to evaluate, in an unprecedented way, its anti-trichomonas activity, in addition to investigating the feasibility of preparing a hydrogel with this suspension, using locust bean gum as a gel-forming agent, aiming at vaginal application for the treatment of trichomoniasis. The nanocapsule suspensions were prepared by the preformed polymer interfacial deposition method and characteristics compatible with nanostructured drug delivery systems were observed, such as average particle size in the nanometric range (193-206 nm), adequate polydispersion index (0.19-0.22), positive zeta potential, pH in the acidic range (4.97-5.04), compound content close to theoretical value (1.04 mg/mL), and high encapsulation efficiency (99.92 %). In the evaluation of the in vitro activity in cells infected by T. vaginalis, (PhSe)2 nanoencapsulated at intermediate concentrations reduced the viability of the trophozoite more significantly compared to the free form of the active, due to controlled release provided by the nanocarrier system. The antioxidant capacity of nanoencapsulated (PhSe)2 was superior to the free form. The mucoadhesion evaluation of the nanocapsules, with change in the average diameter and the inversion of the zeta potential, confirmed their mucoadhesive potential, attributed to the cationic polymer. The hydrogels were prepared by thickening the nanocapsule suspensions with locust bean gum (3%). The developed formulations presented physicochemical characteristics suitable for vaginal application, maintaining the nanometer size in the range of 237-295 nm (photon correlation spectroscopy), active content close to the theoretical value (1mg/g of (PhSe)2) (HPLC), pH values in the neutrality range 6.16-6.20 (potentiometry), as well as non-Newtonian pseudo-plastic behavior (rotational viscometer). The evaluation of the irritation potential by the chorioallantoic membrane method indicated the absence of hemorrhage, coagulation or lysis, demonstrating that the formulations are considered non-irritating. The mucoadhesive strength of hydrogels was improved for the nanoencapsulated active compared to the free (PhSe)2, demonstrating the correct choice of gum. Permeation through the bovine vaginal mucosa using Franz cells showed that the formulations remained on the surface of the vaginal mucosa, which is ideal for the treatment of superficial vaginal infections. Therefore, based on the results obtained, the development of the hydrogel met the proposed therapeutic purpose and could be a promising alternative for the treatment of trichomoniasis. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021-09-27 |
dc.date.accessioned.fl_str_mv |
2022-01-27T19:44:53Z |
dc.date.available.fl_str_mv |
2022-01-27T19:44:53Z |
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/1/23624 |
url |
http://repositorio.ufsm.br/handle/1/23624 |
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 |
dc.relation.authority.fl_str_mv |
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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 |
Desenvolvimento e Avaliação de Produtos Farmacêuticos |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
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Biblioteca Digital de Teses e Dissertações do UFSM |
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http://repositorio.ufsm.br/bitstream/1/23624/1/DIS_PPGCF_2021_REIS_FERNANDA.pdf http://repositorio.ufsm.br/bitstream/1/23624/2/license_rdf http://repositorio.ufsm.br/bitstream/1/23624/3/license.txt |
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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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1793240081058758656 |